bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in brain tyrosine hydroxylase activity following acetylcholinesterase blockade in rats
Authors: Richardson J. Steven , Lamprecht Friedhelm , Kazic Tomislav , Kopin Irwin J.
Published: April 2011

Activation of cholinergic neurons in the brain is produced by administration of the acetylcholinesterase inhibitors physostigmine and diisopropylfluorophosphate (DFP). This activation has a biphasic effect on tyrosine hydroxylase (EC 1.14.3–) activity. The acute effect of DFP, 1 mg/kg, intraperitoneally, or physostigmine, 0.2 mg/kg, intravenously, or 10 μg, intraventricularly, was a rapid reduction in tyrosine hydroxylase activity in the hypothalamus. The activities of DOPA decarboxylase (EC 4.1.1.28) and dopamine-β-hydroxylase (EC 1.14.17.1) were not changed. In contrast to the acute effect, chronic administration of physostigmine, 0.2 mg/kg, intravenously, twice daily for 7 days produced an increase in tyrosine hydroxylase activity in the hypothalamus. The rapid acute effects may be due to an allosteric inactivation of tyrosine hydroxylase, while the chronic effects may reflect enzyme induction.
Light and dark smooth muscle cells in estrogen-stimulated rat myometrium
Authors: Garfield R. E. , Daniel E. E.
Published: April 2011

Smooth muscle cells of different densities to transmission of electrons (termed light and dark cells) were found in rat myometrium examined in the electron microscope following fixation by immersion in glutaraldehyde. Light cells accounted for about 4% of the total population of cells. No light cells were found in tissues fixed in situ by intraarterial perfusion with glutaraldehyde. In addition to staining differences, light cells were distinguished from most dark cells by differences in nuclear, mitochondrial, endoplasmic reticular, and surface structures. The relative number of light and dark cells after in vitro fixation was not changed in tissues relaxed with adrenaline or contracted with oxytocin. Mechanical injury resulted in increased numbers of light cells. Similarly, chemical injury with metabolic inhibitors resulted in ATP depletion, followed by increased numbers of light cells and gain in water content. We concluded that light cells were produced by mechanical or metabolic damage, leading to loss of volume control mechanisms, swelling, and leakage of protein. Light cells found after fixation in vitro in numerous prior studies represent cells damaged during isolation, and not a physiological variant among smooth muscle cells.
Flow rates of components in digesta of pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum, and fed semipurified, hard wheat, and soft wheat diets
Authors: Ivan Michael , Farrell David J.
Published: April 2011

Four pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum were used to study flow rates of total digesta, insoluble dry matter, nitrogen, and amino acids entering and leaving the small intestine. The pigs received a semipurified diet, a hard wheat diet, or a soft wheat diet. These were approximately isonitrogenous.A higher rate of passage of digesta through the proximal duodenum and terminal ileum were measured in pigs receiving the hard wheat diet. Peak flow of digesta at the duodenum of all pigs occurred at 1 h post feeding. Peak flow of digesta at the ileum occurred at 9 h post feeding on the soft wheat diet, but somewhat earlier on the hard wheat and semipurified diet. More nitrogen and essential amino acids flowed in the solid fraction of duodenal digesta during the first 2 h post feeding for the wheat diets and 4 h post feeding for the semipurified diet.It was concluded that flow rate of most nutrients from the stomach and through the small intestine of pigs is modified by the composition and texture of the food ingested. It is postulated that efficiency of mixing of digesta with digestive secretions in the stomach is a major factor influencing rate of flow.
Effect of praseodymium nitrate on hepatocytes and Kupffer cells in the rat
Authors: Tuchweber B. , Trost R. , Salas M. , Sieck W.
Published: April 2011

Intravenous administration of the rare earth metal salt, praseodymium nitrate, induced hepatic damage in the rat, as assessed by morphologic examination (light and electron microscopy) and biochemical parameters (serum glutamic–pyruvic transaminase (EC 2.6.1.2) and glutamic–oxalacetic transaminase (EC 2.6.1.1) activity as well as hepatic triglyceride content). Praseodymium hepatotoxicity was only attained with lower doses (10, 20, or 40 mg/kg), whereas a larger dose (80 mg/kg) was inactive in this respect. As detected by electron microscopy, lower doses of the metal salt caused hepatocytic alterations consisting of degranulation and dilatation of rough endoplasmic reticulum, accumulation of smooth endoplasmic reticulum as well as numerous lipid droplets. No abnormalities were detected in the cell organelles following administration of a large dose of the metal salt; however, vacuoles containing markedly electron-dense material were seen in the cytoplasm of the hepatocytes and the sinusoidal Kupffer cells.
The site of the neuromuscular block produced by polymyxin B and rolitetracycline
Authors: Wright J. M. , Collier B.
Published: April 2011

The site of neuromuscular blockade induced by polymyxin B and rolitetracycline was studied on isolated nerve and nerve–muscle preparations. Polymyxin B (1.8 × 10−4 M) was equipotent to lidocaine as a local anaesthetic on a frog desheathed nerve preparation, while rolitetracycline (up to 3.6 × 10−3 M) had no local anaesthetic effect. Polymyxin B (6 × 10−5 M) and rolitetracycline (7 × 10−4 M) blocked by 50% the response of rat diaphragm induced by phrenic nerve stimulation, but did not decrease the amount of acetylcholine (ACh) released from this preparation during nerve stimulation. Both antibiotics depressed the response of the rat diaphragm to inject ACh, and this response was more sensitive to inhibition by the drugs than was the response to nerve stimulation. With rolitetracycline, a concentration that blocked the response to nerve stimulation by 50% inhibited the response to injected ACh by 85%, and this relationship was similar to that with d-tubocurarine; however, polymyxin B was relatively more effective than d-tubocurarine in inhibiting the effect of ACh. Polymyxin B (1–1.5 × 10−4 M) but not rolitetracycline (1 × 10−3 M) depressed the response of the diaphragm to direct muscle stimulation. It is concluded that polymyxin B and rolitetracycline block neuromuscular transmission predominantly by an effect to depress the muscle's sensitivity to ACh; polymyxin B probably acts by an effect similar to that of local anaesthetics, while rolitetracycline probably acts by an effect similar to that of d-tubocurarinc.
Effects of diphenylhydantoin and phenobarbital on voltage-clamped myelinated nerve
Authors: Neuman R. S. , Frank G. B.
Published: April 2011

Diphenylhydantoin (DPH) and phenobarbital (PB) have a selective action in blocking spontaneous activity in nerves made hyperexcitable by lowering the calcium concentration of the bathing medium (Rosenberg, P. and Bartels, E. 1967. J. Pharmacol. Exp. Ther. 155, 532–544.). To investigate this further, we examined the action of DPH and PB on voltage-clamped single myelinated nerves at two different calcium concentrations. In 1.8 mM calcium Ringer, DPH reduced the sodium permeability (PNa) without affecting the potassium conductance (GK) or the voltage-dependent time constants of sodium activation (τm) and inactivation (τh), and potassium activation (τn). PB was similar to DPH except that in addition to reducing PNa, it shifted τm in the direction of depolarization. When the calcium concentration was lowered to 0.36 mM, the curves relating τm and τh to membrane potential were shifted in the direction of hyperpolarization, as expected. However, the addition of DPH or PB reduced or abolished these shifts. It is suggested that both DPH and PB stabilize hyperexcitable membranes by an action on the parameter m, and that this may contribute to their antiepileptic action.
Effect of glucagon on canine exocrine pancreatic secretion stimulated by a test meal
Authors: Singer Manfred V. , Tiscornia Osvaldo M. , Oliveiro Joao Paulo Mendes de , Demol Pierre , Levesque Denis , Sarles Henri
Published: April 2011

The effect of glucagon on exocrine pancreatic secretion stimulated by a test meal was studied in three dogs with a chronic gastric fistula and a modified Thomas duodenal fistula which allows easier collection of pure pancreatic juice after a meal. Glucagon was given by continuous intravenous infusion in doses of 5, 10, 15, or 30 μg/kg per hour, before and during a test meal. At each dose level glucagon significantly reduced the water and electrolyte secretion of the pancreas. At 15 and 30 μg/kg per hour glucagon inhibited protein output; this effect was absent at lower doses. These findings demonstrate a dose-dependent inhibition by glucagon of the pancreatic bicarbonate and protein response to a meal. Inhibition of bicarbonate output was more sensitive to glucagon than that of protein output.
The effect of ethanol on glucose homeostasis
Authors: Dittmar Elizabeth A. , Hetenyi Jr. G.
Published: April 2011

The effect of an intravenous infusion of ethanol was examined on the rates of hepatic glucose production (Ra) and overall glucose utilization (Rd) in conscious dogs in the postabsorptive state under basal conditions and in insulin-induced hypoglycaemia, after a 4-day fast or in diabetes. The rates were calculated by a tracer infusion method with 3H-labelled glucose as the tracer. The concentrations of glucose, lactate, insulin, and ethanol in plasma or blood were determined, and the rate of ethanol utilization estimated. The infusion of 0.04 or 0.24–0.29 mmol ethanol/kg per minute did not change the concentration of glucose in normal or diabetic dogs in the postabsorptive state, whereas a small decrease in fasted dogs was observed especially when ethanol was infused at the lower rate. Plasma lactate levels were increased; insulin levels did not change. Ra was transiently decreased in fasted dogs, but not in the postabsorptive state in normal or diabetic animals. Ethanol had no effect on the magnitude of the increase in Ra during insulin-induced hypoglycaemia. The estimated rate of ethanol utilization was reduced by fasting but not in diabetes. In conclusion, ethanol did not decrease the elevated rate of gluconeogenesis in diabetic dogs, nor did it interfere with the hepatic response to hypoglycaemia.
Comparison of microspheres and 86Rb+ as tracers of the distribution of cardiac output in rats indicates invalidity of 86Rb+-based measurements
Authors: Foster David O. , Frydman M. Lorraine
Published: April 2011

The technique of using γ-labeled plastic microspheres (15 ± 5 μm) to measure cardiac output (CO) and its fractional distribution (FD) to individual tissues and organs was judged by various criteria to give valid data when applied to barbital-sedated warm-acclimated or cold-acclimated (CA) white rats, which were either resting or responding calorigenically to infused noradrenaline (NA). The FD of CO to each of 16 tissues or organs of CA rats at rest or responding to NA was then estimated both with 86Rb+ and with microspheres, the two tracers being injected simultaneously. For only seven of the tissues examined in resting rats and only one in NA-infused rats was the FD of CO estimated with 86Rb+ not significantly different from that estimated with microspheres. 86Rb+ to microsphere ratios of the FD of CO to individual tissues ranged from 3.5 and 3.0 for liver and skeletal muscle, respectively, down to 0.09 and 0.07 for brown adipose tissue (BAT) and brain. Since microsphere-based estimates of blood flow to the interscapular BAT of CA rats responding to NA were corroborated by direct measurements of venous efflux from the tissue, it is unequivocal that the 86Rb+-based estimate of the fraction of CO directed to interscapular BAT was highly erroneous. When considered along with data from the literature, the present findings support a conclusion that the uptake of 86Rb+ by a tissue frequently does not provide a valid measure of the FD of CO to the tissue. Some of the factors that are likely responsible for this situation are discussed, and it is suggested that only by a fortuitous combination of circumstances does the uptake of 86Rb+ by a tissue sometimes match the FD of CO to the tissue.
Developmental abnormalities induced by 6-mercaptopurine in the hamster
Authors: Shah Ravindra M. , Burdett David N.
Published: April 2011

Pregnant hamsters were given varying doses of 6-mercaptopurine (6MP) at various times during gestation. The fetuses were examined for both gross and histological malformations which showed that the toxic and teratogenic effects of 6MP were dose and time dependent. The most severe gross malformations induced by 6MP were cleft palate, micrognathia and agnathia, microglossia, short limbs, and gut herniation. Grossly normal appearing fetuses, treated during late gestation, showed malformations at the tissue and cellular level. The effects of 6MP in hamster was compared with other specis, and with other growth-supressive agents, and it was deduced that the teratogenicity of 6MP is species and tissue specific. Also, it was recommended that histological observations be made an integral part of the teratological safety analysis.
Responses of pulmonary and systemic circulations of perinatal goats to prostaglandin F2α
Authors: Leffler Charles W. , Tyler Thom L. , Cassin Sidney
Published: April 2011

The effects of exogenous prostaglandin (PG) F2α, as well as PGF1α and the 15-keto metabolites of both prostaglandins, upon unventilated fetal, premature newborn, and mature newborn goat pulmonary and systemic circulations were examined by infusing the compounds into the pulmonary circulation. PGF2α is a powerful pressor agent in both pulmonary and systemic circulations of fetal and neonatal goats. Broncho–pulmonary constriction was also observed in ventilated animals at infusion rates in excess of the lung's ability to catabolize the prostaglandin. The pressor effects were not attenuated by alpha-adrenergic blockade. PGF1α is qualitatively similar, but quantitatively less, in its effect. The 15-keto metabolites did not alter pulmonary or systemic circulation even at very high doses. The PGF2α threshold dose for increasing pulmonary vascular resistance is lowest in the unventilated fetus, greatest in the premature newborn, and intermediate in the newborn older than 1 day of age. The lower sensitivity of the pulmonary circulation to the exogenous vasoconstrictor in the immediate postventilation period suggests the presence of endogenous dilator activity. Since the increase in pulmonary vascular resistance produced by indomethacin is greatest in the newly ventilated fetus, less in the older newborn, and negligible in the unventilated fetus, the substance(s) responsible for the endogenous dilator activity would appear to require prostaglandin fatty acid cyclooxygenase activity for production.
Metabolic responses to status epilepticus in the rat, cat, and mouse
Authors: Howse D. C. N.
Published: April 2011

Prolonged sustained seizure activity (status epilepticus) was created in rats and cats using paralysis and ventilation to prevent muscular contraction and its secondary systemic effects. Under physiologic control, seizure activity was maintained for 30, 60, and 120 min. At this time the brains were frozen using the in situ technique and the cortical tissue was analyzed for energy-related metabolites. The alteration of metabolites found at these times was similar to that previously described in the first 10 min of seizure activity. No evidence was found of any significant or progressive derangement of oxidative metabolism. A progressive lactic acidemia developed in spite of adequate arterial oxygen tensions.In contrast, when mice received a similar dose of the convulsant and were allowed to convulse freely in an oxygen-enriched environment, major derangements of energy metabolism were found which were progressive and persisted following recovery for at least 18 h.
Organic mercurial diuresis: Inhibition of glutamine utilization in the acidotic rat
Authors: Passerini Louise , Welbourne T. C.
Published: April 2011

Organic mercurials inhibit mitochondrial glutamine metabolism in vitro while metabolic acidosis, a condition in which the predominant renal fuel is glutamine, potentiates mercurial diuresis. The following studies were undertaken to determine whether potentiation of diuresis reflects mercurial inhibition of glutamine utilization.(1) All three mercurials employed (mersalyl, chlormerodrin, and p-chloromercuribenzoate) are diuretics in the rat and this effect was potentiated by NH4Cl.(2) Despite reabsorbing less sodium, mercurial-treated rats had lower kidney ATP content (4.35 ± 0.26 and 3.85 ± 0.43 μmol/g dry weight (mercurial plus NH4Cl)) than did controls (4.95 ± 0.31 and 4.87 ± 0.39 μmol/g dry weight (NH4Cl)).(3) Isolated kidneys from NH4Cl and NH4Cl plus mercurial treated rats were perfused with 1 mML-[U-14C]glutamine to determine rates of extraction and oxidation. Mercurial-treated acidotic rat kidneys had a reduced rate of glutamine uptake (40.8 ± 7.4 vs. 64.8 ± 5.8 μmol/h. per kidney), a diminished rate of glutamine conversion to CO2 (14.8 ± 3.6 vs. 26.4 ± 5.2 μmol/h per kidney), and a reduction in glucose production (16 ± 5 vs. 27 ± 4 μmol/h per kidney). These results are consistent with an effect of organic mercurials upon glutamine utilization, limiting ATP availability, and thereby reducing tubular active sodium reabsorption.
Control of stiffness by the medium latency electromyographic response to limb perturbation
Authors: Kwan Hon C. , Murphy John T. , Repeck Marilyn W.
Published: April 2011

It is hypothesized that the medium latency electromyographic (EMG) response (ML) to limb perturbation functions to preset limb stiffness to a constant initial level. Three predictions are derived from this hypothesis: Firstly, in the presence of an instruction calling for opposition to limb perturbation, a control signal, ML, will be observed and will lead to the establishment of a constant level of limb stiffness. Secondly, in the absence of an instruction to oppose, no control signal will be observed and correspondingly a constant stiffness will not be generated. Thirdly, the latency of onset of stiffness control will covary with the latency of onset of ML. These predictions were tested in experiments involving perturbation of the human forearm about the elbow joint, with surface EMG measurements and computation of the limb stiffness function. The results are in accord with these predictions, and support the hypothesis that ML functions in the feedforward control of limb stiffness.
Changes in platelet function and gastrointestinal bleeding following repeated administration of acetylsalicylic acid in the rat and the dog
Authors: Mills D. G. , Lane I. J. , Otton J. D. , Cook M. A. , Philp R. B.
Published: April 2011

Two dogs were prepared with Pavlov pouches of the fundic area of the stomach using standard techniques. During treatment periods of 14 days, 200 mg acetylsalicylic acid (ASA) was introduced into the pouch twice daily by insufflation. One hour after each drug administration the pouch was washed with saline and the fluid assayed for blood. Bleeding from the pouch increased to a maximum on the 3rd or 4th day of the treatment period and subsequently declined such that by the 8th day blood loss was minimal and approximated that found during control periods. Platelet aggregation (in vitro) responses to adenosine diphosphate were significantly (p < 0.01) inhibited on day 3 when aggregation curve heights were reduced by 66.2 ± 13.11% (mean ± SEM) from control values. On day 7 and during the ensuing 7-day period when ASA was given twice daily, the heights of aggregation responses were reduced by only 20–30% from controls. These responses were significantly (p < 0.001) greater than those found on day 3. Similar changes in platelet reactivity were found in plasma from rats given ASA twice daily for 7 days. Aggregation responses to collagen were depressed by 95.5 ± 4.49% on day 1 following two doses of ASA. As the treatment period continued, the aggregation responses increased in magnitude until the 7th day they were similar in height to those from control animals. The mechanism involved in this adaptation to ASA treatment seen with these platelets is not known.
Cytochrome P-450 and hepatic drug biotransformation during progressive cardiac disease in cardiomyopathic hamsters
Authors: Renton Kenneth W. , Baker James C. , Bailey Leslie E.
Published: April 2011

Reductions in cytochrome P-450 levels and aminopyrine N-demethylase activity of hepatic microsomes obtained from cardiomyopathic hamsters (BIO 14.6) occurred at all stages of the disease before the development of congestive heart failure (CHF). Cytochrome b5 levels were reduced only in animals with CHF when compared with age-matched controls (BIO.RB). Total microsomal protein and p-nitrophenol glucuronidation were not affected by the disease process. We conclude that the reduction in cytochrome P-450 levels and N-demethylase activity in cardiomyopathic hamsters is not a consequence of CHF, but is one of the manifestations of the disease process.
Erythrocyte ghost – buffer partition coefficients of phenobarbital, pentobarbital, and thiopental support the pH-partition hypothesis
Authors: Korten Klaus , Miller Keith W.
Published: April 2011

The partition coefficient (λ) between red cell ghosts and buffer has been determined for three barbiturates over a range of pH. Experimental partition coefficients were linearly proportional to the calculated degree of association of the barbiturates. λ was 9.5 ± 0.52 for phenobarbital, 12.7 ± 0.91 for pentobarbital, and 27 ± 4.9 for thiopental in their acid forms. λ for all three barbiturates in their anionic forms was zero. Our data support the assumption of the pH-partition hypothesis that the dependence of λ on pH in biological membranes behaves essentially like that in organic solvents. However, the relative magnitudes of the erythrocyte partition coefficients correlate much more closely with the physiological permeability constants than do those of organic solvents, which tend to overestimate the differences between these compounds.
Dopamine modulation of gill reflex behavior in Aplysia
Authors: Ruben Peter , Lukowiak Ken
Published: April 2011

We have studied the effects of dopamine on the gill withdrawal reflex evoked by tactile siphon stimulation in the margine mollusc Aplysia. Physiological concentrations of dopamine (diluted in seawater) were perfused through the gill during siphon stimulation series. The amplitude of the reflex was potentiated by dopamine and habituation of the reflex was prevented. This occurred with no change in the activity evoked in central motor neurons. These results lead us to conclude that the dopaminergic motor neuron L9 is modulating habituation in the periphery and that the central nervous system facilitatory control of the peripheral nervous system may act via a dopaminergic pathway.
Effeet of pentobarbital anesthesia and laparotomy on plasma renin activity in the dog
Authors: Yun John C. H. , Donahue James J. , Bartter Frederic C. , Kelly Gerald D.
Published: April 2011

The effects of sodium pentobarbital and laparotomy on plasma renin activity (PRA) were examined in the dog with or without pretreatment with indomethacin. In control experiments, sodium pentobarbital (30 mg/kg, iv) caused PRA to rise from 9.98 ± 1.48 ng mL−1 h−1 (mean ± SEM) during control periods to 22.49 ± 3.52 ng mL−1 h−1 30 min after the administration of sodium pentobarbital (P < 0.005). Sixty minutes after the induction of anesthesia, PRA was 14.21 ± 2.93 ng mL−1 h−1 (0.005) < P < 0.1). In these animals, PRA was 12.92 ± 2.31 ng mL−1 h−1 (P > 0.1) 4 h after laparotomy. Subsequent nonhypotensive hemorrhage in these animals (7.5 mL/kg) caused PRA to rise to 21.69 ± 2.63 ng mL−1 h−1 30 min after hemorrhage (P < 0.005).In the animals treated with indomethacin (5 mg/kg, followed by 2.6–3.3 mg kg−1 h−1), PRA was 3.60 ± 1.20 ng mL−1 h−1 during control periods and 4.77 ± 1.71 ng mL−1 h−1 30 min after the injection of indomethacin (P > 0.1). Pentobarbital anesthesia in these animals caused PRA to rise to 15.59 ± 3.54 ng mL−1 h−1 30 min after the administration of pentobarbital (P < 0.005). PRA was still 9.91 ± 3.18 ng mL−1 h−1 60 min after the administration of pentobarbital (P < 0.01). In these animals, PRA was 12.60 ± 3.27 ng mL−1 h−1 4 h after laparotomy (P > 0.1). Subsequent nonhypotensive hemorrhage caused PRA to rise to 18.67 ± 2.97 ng mL−1 h−1 30 min after hemorrhage (P < 0.005).The data show that indomethacin does not prevent the increase in PRA produced by pentobarbital anesthesia. The data further show that laparotomy does not appear to cause an increase in PRA in the dog as in the rabbit.
Teratogenic effects of diazepam in the hamster
Authors: Shah Ravindra M. , Donaldson David , Burdett David
Published: April 2011

Pregnant hamsters were treated with different doses of oral and intravenous diazepam during the period of organogenesis. Teratogenic effects of diazepam were observed following oral treatment on days 8 and 10 and following intravenous treatment on day 11 of gestation. Types of malformations included cleft palate, exencephaly, limb anomalies, and hemorrhage. A dose–effect relationship was not observed. Comparison with reported literature seems to indicate that diazepam may be a mild teratogen in some species.
The effects of temperature, local anaesthetics, pH, divalent cations, and group-specific reagents on repriming and repolarization-induced contractures in frog skeletal muscle
Authors: Foulks J. G. , Perry Florence A.
Published: April 2011

Contractures appear during repolarization of frog toe muscles in media containing perchlorate in place of chloride. These contractures were suppressed or delayed by certain procedures which retard the repriming of K contractures, i.e., by sufficient reduction in temperature or by alkaline pH in solutions lacking divalent cations. They also were greatly reduced without interference with repriming after treatment with a reagent which selectively modifies free amino groups. In the presence of appropriate concentrations of procaine, repriming was markedly impaired with only a small reduction in the amplitude of repolarization-induced contractures. Small contractures were produced during repolarization in chloride solutions in the presence of 10 mM procaine at pH 8.0. None of these procedures affected the changes produced by perchlorate solutions in the potential dependence and the time course of K contractures. The results support the view that activation and inactivation of contraction following depolarization are separate potential dependent processes. Tension appears to develop during repolarization when the reversal of inactivation occurs before the reversal of activation is completed, both steps being necessary to recover the reprimed resting state.
A novel method to separate the layers of the intestine
Authors: Hiebert L. , Jaques L. B.
Published: April 2011

By applying cellulose acetate paper to the lumenal and serosal surface of the intestine of rats, we have divided the intestine into three layers. Examining the layers histologically, we have shown that most of the villi are removed from the mucosal surface, the serosa alone is removed from the serosal surface, and the portion remaining consists of the crypt, submucosa, and muscle layers. This appears to provide a rapid procedure for separation of the layers of the intestine for histological and biochemical studies.
Improved Isolation of villus and crypt cells from rat small intestinal mucosa
Authors: Hoffman Alan G. D. , Kuksis Arnis
Published: April 2011

An enzymic method is described which allows the isolation under comparable conditions of crypt and villus cells from rat jejunum with normal morphologic appearance and high metabolic activity when compared with previous preparations. The method is based on a differential scraping of short lengths of everted small intestine to yield two villus cell fractions and a gut wall residue. The scrapings and the gut tube are incubated for the same length of time in a HEPES-buffered modified Hanks' balanced salt solution containing hyaluronidase, DNase, and soybean trypsin inhibitor. The cells of the crypt region are recovered by a further scraping of the digested gut wall. Cells from all fractions are dispersed by gentle agitation, washed, and harvested by centrifugation. The final crypt and villus cells are 95–99% viable by dye exclusion and exhibit 5–20% cross-contamination on the basis of differential marker enzymes. The isolated crypt and villus cells prepared by the new procedure are suitable for comparative studies of metabolic activity in the absence of chelation-induced structural and metabolic abnormalities.
Net fluxes of electrolytes in the rat intestine infected with Moniliformis dubius (Acanthocephala)
Authors: Mettrick D. F. , Budziakowski M. Eva , Podesta R. B.
Published: April 2011

The effect of Moniliformis dubius on fluxes of Na+, K+, Cl−, and HCO3− in the rat intestine was determined using a conventional in vivo single-pass perfusion technique.Results for ion and water movements in the uninfected gut were in agreement with previous studies. In the parasitized intestine the jejunal pH was significantly lower than that in control animals, matching the restriction of the parasites to this region of the small intestine. While parasitism did not affect Na+ transport in the distal ileum, Na+ absorption was reduced (pH 7.0), or secretion enhanced (pH 6.0), in the two proximal regions. Cl− absorption was reduced in the distal ileum, but secretion was enhanced in the other two segments. Parasitism also enhanced K+ secretion in all segments. Net H2O absorption was reduced at pH 7.0; at pH 6.0 net secretion was also reduced. These changes clearly indicate that a parasite restricted to the jejunum may significantly affect the absorptive and secretory activity of the intestine distal to the site of infection.The results are discussed in the light of current concepts of electrolyte transport. The effect of the parasites on mucosal function distal to their site of attachment is discussed in terms of the release by the parasite of toxin-like substances, changes in the physical–chemical characteristics of the intestinal lumen, and interference with neurohormonal control of gastrointestinal function.
Changes in skeletal muscle glycogenolysis after prolonged cold exposure and repeated injections with isoproterenol
Authors: Thibault M. C. , Côté C. , Vallières J.
Published: April 2011

Wistar rats were either given daily injections of isoproterenol (ISO) (15 μg/100 g per day) or exposed to 6 °C for 4 or 12 weeks (cold acclimated (CA)). After a 4-week exposure to cold and to ISO, acute cold stress (4 h at –18 °C) produced a 48% depletion of glycogen in the tibialis anterior of control rats while it did not significantly affect the levels in ISO-treated and CA animals. ISO treatment enhanced the in vivo response of phosphorylase kinase and glycogen phosphorylase to epinephrine (EPI) in the tibialis anterior, a fast contracting muscle. In the soleus, a slow contracting muscle known to be more sensitive to catecholamines, chronic treatment with ISO also resulted in increased basal and EPI-stimulated adenylate cyclase activity. No evidence could be found for an alteration of the glycogenolytic pathway (adenylate cyclase system, phosphorylase kinase, and glycogen phosphorylase) in fast contracting skeletal muscles of CA rats. It is concluded that ISO-treated and CA rats, which have a great capacity for nonshivering thermogenesis, do not rely on their muscle carbohydrate reserves during cold stress. It might be suggested that plasma levels of catecholamines higher than those produced by exposure to 6 °C are required to alter glycogenolytic mechanisms in fast contracting rat skeletal muscles.
Biological activities of kinins modified at the N- or at the C-terminal end
Authors: Drouin J.-N. , Gaudreau P. , St-Pierre S. , Regoli D.
Published: April 2011

A series of analogues of des-Arg9-bradykinin, modified at the N- or C-terminal end, were tested on rabbit aorta strips (receptor B1) and on cat ileum strips (receptor B2) in an attempt to find long-acting agonists and antagonists. It was found that the methylation or the amidation of the C-terminal carboxyl reduces the affinity and (only the amidation) the intrinsic activity of the agonists, while not changing significantly the duration of action of both agonists and antagonists.The addition of a Lys at the N terminal is accompanied by a marked increase of affinity, no changes of intrinsic activity, and a prolongation of the duration of action of agonists. Antagonists behave in a similar way as the agonists and show increased affinity; the time required for inducing full inhibition as well as the duration of action are significantly increased.The pharmacological and physiopathological implications of these results are discussed.
The irreversible binding of benzo[a]pyrene to rat liver macromolecules in vivo and in vitro: Effects of agents that influence benzo[a]pyrene metabolism
Authors: Gontovnick L. S. , Ng S. , Bellward G. D.
Published: April 2011

The present study was carried out to determine the effects of agents that influence benzo[a]-pyrene(BP)metabolism in vitro on the irreversible binding of BP to rat hepatic macromolecules in vivo. The irreversible binding of [3H]BP was found to be both dose and time dependent after its intraperitoneal administration to male Wistar rats. The SKF 525-A, at doses of 50 and 75 mg/kg, ip, 3 h before BP, decreased the level of binding from control by 31 and 34%, respectively. At 35 mg/kg, SKF 525-A had no effect. Diethyl maleate (0.6 mL/kg, ip) and cysteine (150 mg/kg, ip), 30 and 5 min before BP, respectively, did not alter the binding of BP from control. Oral methadone treatment, previously shown to increase selectively epoxide hydrase activity in male Wistar rats, also failed to alter the amount of BP bound to hepatic macromolecules. 3-Methylcholanthrene (20 mg/kg per day, ip, for 2 days) administered 24 h before BP, decreased the level of binding from control by.30%. Parallel in vitro studies were carried out with the various agents used in vivo.
Myotropic affinities of angiotensin II and des-Asp1-angiotensin II in rabbit aorta and femoral artery by microassay
Authors: Waugh William H. , Bales Theodore E.
Published: April 2011

Dose-dependent isometric contractions to [Asp1,Ile5]-angiotensin II (AII) and des-Asp1-[Ile5]-angiotensin II (AIII) were obtained with 3-mm-wide rings of rabbit thoracic aorta and femoral artery in microbaths. A period of 2.5–3 h was required to obtain reproducible contractile responses of increased sensitivity. Contractions developed faster and they were much more forceful but less sustained in femoral arterial rings than in aortic rings. Noncumulative dose–response curves with AII and AIII were parallel and reached the same maximum. Peak contractile responses were linearly proportional to the receptor stimulation predicted from the mass action equation and the concept of intrinsic activity relating bath dosage of agonist to the number of myotropic receptors occupied by AII and by AIII. These findings validated measurement of the myotropic affinities of both tissues for AII and AIII by the obtained ED50 values. In 0.6-mL baths, developed with the use of a meshed screen for reoxygenation, the apparent affinities of aortic muscle for AII and AIII averaged 0.149 and 0.0030 nM, respectively. The mean affinities were much greater at 0.594 and 0.236 nM, respectively, in femoral arterial muscle. The myotropic affinity for AIII relative to that for AII averaged 2.26% in the aorta but 40.8% in the femoral artery. The apparent affinities were reduced and contractions less forceful in 0.24-mL baths without regassing. The results suggest that AII and AIII may stimulate the same angiotensin receptors in aorta and femoral artery and that the receptors may be different in structure or immediate environment in these two vascular tissues.
Prostaglandin actions and interactions on isolated perfused rat hearts
Authors: Karmazyn M. , Leung C. K. H. , Dhalla N. S.
Published: April 2011

The actions of prostaglandins (PGs) D2, E1, E2, F2α, and I2 and interactions between these agents were examined using the isolated Langendorff-perfused rat heart. In concentrations between 2.8 × 10−11 and 2.8 × 10−7 M, PGE2, PGD2, and PGF2α produced an increase in coronary perfusion pressure while PGE1 addition resulted in a decrease. The PGI2 constricted the coronary vessels at 2.8 × 10−10 M although higher concentrations resulted in dilatation. The PGF2α produced significant increases in the contractile force but negative inotropic effects were seen with PGE1. The PGI2 actions on myocardial contractility were biphasic. Variable changes were seen with regard to resting tension after PG administration. Complex interactions were noted when PGs were examined in the presence of other PGs or arachidonic acid. Prior addition of either PGE2 (2.8 × 10−10 M) or arachidonic acid (2.8 × 10−7 M) inhibited or reversed various actions of PGD2 on the heart. The coronary and myocardial effects of PGE1 were usually influenced by the presence of most other PGs as well as arachidonic acid. Arachidonic acid, PGF2α, and PGE1 attenuated the coronary constricting and positive inotropic actions of PGE2. The PCL1 reversed the positive inotropic effects of PGF2α. When added alone, PGI2 had slight coronary-constricting actions but in the presence of other agents a biphasic effect was seen. The PGI2 increased the myocardial contractile force significantly only in the presence of PGF2α. These results suggest diverse actions of PGs within a wide concentration range and suggest that PG actions may be influenced by the presence of other PG substances.
Effect of ergocristine on prolactin secretion in the male rat with pituitaries grafted beneath the kidney capsule
Authors: Shin S. H.
Published: April 2011

Male rats in which three pituitaries were grafted beneath the kidney capsule showed approximately a fourfold increase in circulating plasma prolactin concentration. The elevated plasma prolactin concentration did not remain at a constant level but fluctuated with time. The elevated prolactin concentration declined immediately after a single bolus injection of ergocristine (30 μg/kg). The slope of the prolactin decay curve, determined by sequential blood sampling, was parallel to a theoretical slope having a 7-min half-life. This result indicates that ergocristine blocked prolactin secretion immediately and completely as the decay curve (T1/2 = 6.5 min, confidence interval 4.5–11.3) resulting from the administration of ergocristine is the same as the endogenous prolactin decay curve (T1/2 = 7 min).
Effect of synthetic cyclic nucleotides on immunologic histamine release from calf granulocytes
Authors: Perron R. J. , Eyre P.
Published: April 2011

Sensitized bovine granulocytes release histamine when exposed to specific antigens. A unique modulation of histamine release by adrenergic agents has been shown in the bovine; β-adrenergic agonists enhance and α-adrenergic agonists inhibit histamine release. This is an opposite response to that reported in other species. The present study was undertaken to determine the possible relationship between cyclic nucleotides and adrenergic agents in this species.Dibutyryl cAMP enhanced antigen-induced histamine release over the complete concentration range tested (10−6–10−3 M); it also overcame, in a dose-dependent manner, the inhibition of antigen-induced histamine release produced by 10−4 M phenylephrine. The 8-bromo cGMP and 0-monobutyryl cGMP had no significant effect on antigen-induced histamine release nor did 8-bromo cGMP have any significant effect on the enhancement of histamine release produced by 10−4 M dibutyryl cAMP. These findings suggest that only cAMP has a role in the modulation of antigen-induced histamine release from bovine granulocytes.
The effect of magnesium-free solutions on the responses of the guinea pig urinary bladder to adenosine 5′-triphosphate and nerve stimulation
Authors: Johns A.
Published: April 2011

Exposure of the guinea pig urinary bladder to magniesium-free Krebs–Henseleit type solution for 60 min led to an increase in the responses of the tissue to added adenosine 5′-triphosphate (ATP). The responses of the tissue to histamine were unaffected. The atropine-resistant contractions due to nerve stimulation were potentiated at frequencies above 4 Hz when the response of the tissue was 60% of its maximum response. This would suggest that, although ATP does contribute to the responses of the tissue at high frequencies, it is not the transmitter of the noncholinergic nerves present in the bladder.
Hippocampal seizures and failure of inhibition
Authors: Ben-Ari Y. , Krnjević K. , Reinhardt W.
Published: April 2011

The powerful inhibition of CA3 pyramidal neurons evoked in rats (under urethane) by stimulating the fimbria or the perforant path from the entorhinal area is associated with a large increase in input conductance. Microiontophoretic applications of GABA produce a very similar large conductance increase, which is characterized by rapid fading, and causes a marked depression of the inhibitory postsynaptic potential (IPSP) conductance change. During repetitive stimulation at frequencies as low as 3–5/s, the IPSP conductance change can be much reduced, and it vanishes when electrical seizures begin. Since the effect of GABA is also reduced or abolished, a loss of efficacy of GABA (caused by desensitization or some other process) may be responsible for the failure of inhibition observed during tetanic stimulation, as well as for the subsequent seizures.
The role of calcium in the control of renin release from the isolated rat kidney
Authors: Logan Alexander G. , Chatzilias Alice
Published: April 2011

The effect of verapamil and manganese on isoproterenol- and glucagon-evoked renin secretion and on norepinephrine-induced renal vasoconstriction was studied in the isolated perfused kidney. Results for renin secretion and perfusate flow rates were expressed as the ratio of the average of the two values which deviated furthest from base line during the experimental period to the average of two control values determined at the beginning of each experiment. Norepinephrine significantly reduced (p < 0.001) the perfusate flow ratio to 0.35 ± 0.06 (mean ± SEM) without having any effect on renin secretion. During Ca2+-free perfusion, norepinephrine-induced renal vasoconstriction was completely abolished and concomitantly the renin secretion ratio increased significantly (p < 0.001) to 6.28 ± 1.24. Verapamil attenuated and manganese chloride abolished norepinephrine-induced renal vasoconstriction. Renin secretion increased significantly (p < 0.001) to 9.26 ± 1.79 and 9.92 ± 1.93 in the verapamil and manganese experiments, respectively. Verapamil and manganese themselves did not significantly alter renin secretion or perfusate flow and neither inhibited renin secretion induced by isoproterenol and glucagon. In conclusion, extracellular Ca2+ and net Ca2+ influx are prerequisites for norepinephrine to produce renal vasoconstriction and to inhibit renin release in the isolated perfused kidney. On the other hand, renin secretion evoked by isoproterenol and glucagon does not seem to require the movement of extracellular calcium into juxtaglomerular cells and it is speculated that the level of adenylate cyclase activity may be an important determinant of the rate of renin release.
The temperature dependence of ionic influences on contractile function in frog twitch muscle
Authors: Foulks J. G. , Morishita Lillian
Published: April 2011

Alterations in the ionic composition of the medium produce striking changes in the potential-dependent contractile responses of skeletal muscles. This study was undertaken to examine the temperature dependence of some of these effects. The suppression of maximal K contractures of frog toe muscles in media lacking divalent cations was largely overcome by a sufficient increase in temperature. The restoration of K contractures by perchlorate in the absence of divalent cations was prevented by a sufficient decrease in temperature. The effect of perchlorate was to shift the temperature dependence of these contractures toward lower temperatures. The reduction in the amplitude of maximal K contractures in the absence of divalent cations was less marked after pretreatment with a reagent (trinitrobenzenesulfonate) that selectively modifies free amino groups, although the temperature dependence of these contractures was unchanged. The reduction in the amplitude of K contractures in the presence of an organic anion (hexanoate) was partially antagonized both by an increase in temperature or by a decrease in temperature, effects that resemble those observed in solutions in which the divalent cation concentration was reduced. In chloride solutions, the relation between [K]0 and K contractures was shifted toward lower [K]0 by an increase in temperature, whereas in perchlorate solutions increased temperature produced a shift in the opposite direction. The shift in this relation toward lower [K]0 at reduced temperature, and the accelerated time course of K contractures with an increase in temperature were similar in perchlorate and in chloride solutions. Thermodynamic analysis by Arrhenius plots indicated that the influence of divalent cations and perchlorate anions on K contractures may be the result of their effects on hydrational factors.
Passage of iron out of the intestinal mucosa of the rat
Authors: Thomson A. B. R. , Valberg L. S.
Published: April 2011

To determine the effect of removal of the "lumen-to-mucosa" concentration gradient on the passage of iron (Fe) out of the intestine, duodenal loops of rats with loaded (FeL) or deficient (FeD) iron stores were perfused for 30 min with 5.0 mM solutions containing 59Fe. The test solutions were then removed and in vivo perfusion of the washed mucosa was continued for up to 60 min with saline or unlabelled Fe–saline. Despite the greater initial uptake of Fe by FeD than FeL, continued perfusion with saline was associated with the appearance of similar quantities of 59Fe in the perfusate; in contrast, when perfusion was continued with Fe-saline, the loss of 59Fe into the perfusate was increased and was twice as great in FeD as in FeL. Iron transfer to the carcass was higher in FeD than in FeL, but continued perfusion with saline was associated with the appearance of increased amounts of 59Fe in the carcass of FeL but not FeD; the amount of 59Fe appearing in the carcass was greatly increased in both FeD and FeL by continued perfusion with Fe–saline. Thus, the amount of 59Fe available for entry into the intestinal lumen and carcass after removal of the lumen-to-mucosa concentration gradient is influenced by the size of the body iron stores and by the presence of iron in the fluid remaining in the lumen. Therefore, the amount of iron in the fluid remaining in the intestinal lumen after the administration of the Fe test dose must be carefully defined when estimating the kinetics of the intestinal absorption of iron.
Amygdala lesions and 24-h variation in plasma corticosterone, growth hormone, and prolactin levels
Authors: Seggie Jo
Published: April 2011

The effects of destruction of the whole amygdala complex on 24-h variations in resting corticosterone, growth hormone, and prolactin levels were investigated in male rats. All three hormones showed the expected resting levels and 24-h variations as previously reported. Bilateral destruction of the amygdala had no effect on either the resting levels or the 24-h variations of these hormones. Thus integrity of the amygdala is not essential for the normal basal and diurnal hormone profile of corticosterone, growth hormone, and prolactin.