bluuebunny/crossref_metadata_2025 huggingface dataset:
Vagal afferent activity and body temperature in 3 to 10-day-old and adult rats
Authors: Trippenbach Teresa
Published: April 2011

This study examined the possible contribution of vagal stretch receptor activity to the increased power of the Hering-Breuer reflex in hyperthermia in rats during the early postnatal period. Experiments were performed on 10 anesthetized (pentobarbital 40 mg/kg, ip) 3 to 10-day-old (body weight of 16 ± 1 g; SE) and, for comparison, 18 adult Sprague-Dawley rats (body weight of 336 ± 35 g). Animals were tracheostomized and artificially ventilated with oxygen. The left vagus nerve was cut. In adult animals, single receptor fibers or a bundle of a few fibers were recorded using a bipolar stainless-steel electrode under mineral oil. In the young rats, a suction electrode filled with normal saline was used. Positive pressure of either 5 or 10 cmH2O was applied to the trachea when the respirator was turned off. The vagal activity was amplified and monitored on a storage oscilloscope for calculation of the frequency of vagal afferent activity during a given pressure application at different rectal temperatures (TR; range 28 to 42°C). In total, 30 and 31 sets of vagal activity in the young and adult rats, respectively, were analyzed. In all cases, an increase in tracheal pressure (PTR) from 5 to 10 cmH2O increased the frequency of vagal firing. The increase was greater in the adult versus the young animals; at 36°C the increase was 49 ± 11% and 16 ± 3% in the adult and young rats, respectively (P < 0.01). In all animals, vagal receptors showed temperature-sensitivity, but less so in the young than in the adult rats (P < 0.0004 and P < 0.003; for PTR of 5 and 10 cmH2O, respectively). In addition, the relationship between temperature-sensitivity and TR had significant slopes (P < 0.001 for both inflation pressures) in the adults but not in the young rats, indicating that in the latter the temperature-sensitivity of vagal receptors is independent of TR. These results imply that temperature-sensitivity of vagal receptors could have contributed to the increased power of the Hering-Breuer reflex in rats during the early postnatal period in the warmer environment.Key words: vagal receptors, temperature, Hering-Breuer reflex, young, adults, rats.
Eicosatetraynoic acid (ETYA), a non-metabolizable analogue of arachidonic acid, blocks the fast-inactivating potassium current of rat pituitary melanotrophs
Authors: Kehl S J
Published: April 2011

The effects of arachidonic acid (5,8,11,14-eicosatetraenoic acid, AA) and 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, were examined on the transient [IK(f)] and the delayed rectifier-like [IK(s)] voltage-gated potassium currents in rat pituitary melanotrophs. The main questions addressed were whether AA and ETYA blocked IK(f) and if any blocking action was specific. Macroscopic currents were measured using the patch clamp technique. Bath application of 20 µM AA reduced IK(f), however, the degree of the block varied between cells. In contrast, ETYA consistently inhibited IK(f). Fitting of the charge transfer or the peak current amplitude yielded KD estimates for ETYA of 1.2 µM and 3.3 µM, respectively. The reduction by ETYA of peak IK(f) was always associated with an increased rate of current decay, but there was no detectable change of the kinetics of activation. ETYA caused a small left shift of the IK(f) steady-state inactivation curve and significantly slowed recovery from inactivation. At 20 µM, ETYA also reduced IK(s), indicating that it is not specific. The possibility that ETYA acts as an open-channel blocker is discussed.Key words: transient potassium current, melanotroph, eicosatetraynoic acid, ETYA, arachidonic acid.
Changes in skeletal muscle in males and females following endurance training
Authors: Carter S L , Rennie C D , Hamilton S J , Tarnopolsky M A
Published: April 2011

Gender differences in substrate selection have been reported during endurance exercise. To date, no studies have looked at muscle enzyme adaptations following endurance exercise training in both genders. We investigated the effect of a 7-week endurance exercise training program on the activity of β-oxidation, tricarboxylic acid cycle and electron transport chain enzymes, and fiber type distribution in males and females. Training resulted in an increase in [Formula: see text]O2peak for both males and females of 17% and 22%, respectively (P < 0.001). The following muscle enzyme activities increased similarly in both genders: 3-β-hydroxyacyl CoA dehydrogenase (38%), citrate synthase (41%), succinate-cytochrome c oxidoreductase (41%), and cytochrome c oxidase (COX; 26%). The increase in COX activity was correlated (R2 = 0.52, P < 0.05) with the increase in [Formula: see text]O2peak/ fat free mass. Fiber area, size, and % area were not affected by training for either gender, however, males had larger Type II fibers (P < 0.05) and females had a greater Type I fiber % area (P < 0.05). Endurance training resulted in similar increases in skeletal muscle oxidative potential for both males and females. Training did not affect fiber type distribution or size in either gender.Key words: endurance training, oxidative potential, gender.
Effect of chronic and progressive aortic constriction on renal function and structure in rats
Authors: Gallego B , Arévalo M A , Flores O , López-Novoa J M , Pérez-Barriocanal F
Published: April 2011

The purpose of this study was to evaluate the functional and structural renal damage observed in aortic-constricted hypertensive rats and to identify their possible relationship with transforming growth factor β (TGF-β) expression. Progressive renovascular hypertension was induced by progressive aortic constriction between the two renal arteries. Three months after constriction, the glomerular filtration rate (GFR), effective renal blood flow (ERBF), perfusion pressure (PP), urinary protein excretion (UPE) and urinary electrolyte excretion (UNaV and UKV) in the kidney above (right kidney, RK) and below the ligature (left kidney, LK) were measured. The cross-sectional corpuscular, capillary tuft and mesangial matrix area and tubulo-interstitial fibrosis were measured in tissue sections stained with Syrius Red using a computer-assisted image analysis system. TGF-β was detected by immunohistochemistry. The functional parameters were similar in the two kidneys of aortic-constricted hypertensive rats (GFR-RK, 1.33 ± 0.08 vs. LK, 1.18 ± 0.08 mL/min; ERBF-RK, 9.23 ± 1.32 vs. LK, 8.18 ± 0.91 mL/min; RVR-RK, 28.3 ± 3.9 vs. LK, 21.7 ± 3.2 mmHg·min/mL). The RK was subject to a higher PP than the LK (176 ± 7 vs. 128 ± 5 mmHg, P < 0.05). UPE, UNaV, and UKV were greater in the RK than in the LK (UPE-RK, 512 ± 61 vs. LK, 361 ± 38 µg/30 min, P < 0.05; UNaV-RK, 0.056 ± 0.012 vs. LK, 0.022 ± 0.006 mEq/30 min, P < 0.05; UKV-RK, 0.042 ± 0.006 vs. LK, 0.029 ± 0.003 mEq/30 min, P < 0.05). Morphometric analysis revealed that the RK capillary tuft area and mesangial matrix area were higher than those in the LK. The LK had a higher degree of interstitial fibrosis than the RK. No significant differences in TGF-β immunostaining were observed between the RK and the LK. In conclusion, the RK (subjected to hypertension) of aortic-constricted hypertensive animals developed glomerular fibrosis, only in the outer glomeruli whereas the LK developed mild interstitial fibrosis. Neither glomerular nor interstitial fibrosis seem to be responsible for the proteinuria observed in both kidneys.Key words: renovascular hypertension, renal fibrosis, rats, TGF-β.
Detailed analysis of the atrial natriuretic factor receptor hormone-binding domain crystal structure
Authors: Akker Focco van den
Published: April 2011

The X-ray crystal structure of the dimerized atrial natriuretic factor (ANF) receptor hormone-binding domain has provided a first structural view of this anti-hypertensive receptor. The structure reveals a surprising evolutionary link to the periplasmic-binding protein fold family. Furthermore, the presence of a chloride ion in the membrane distal domain and the presence of a second putative effector pocket suggests that the extracellular domain of this receptor is allosterically regulated. The scope of this article is to extensively review the data published on this receptor and to correlate it with the hormone-binding domain structure. In addition, a more detailed description is provided of the important features of this structure including the different binding sites for the ANF hormone, chloride ion, putative effector pocket, glycosylation sites, and dimer interface.Key words: crystal structure, periplasmic-binding protein fold, guanylyl cyclase, hormone receptor.
Intravenous lipid composition affects hypoxic pulmonary vasoconstriction in the newborn piglet
Authors: Barrington Keith J , Chan George , Aerde John E. Van
Published: April 2011

To examine the effects of altering the fatty acid (FA) composition of intravenous (IV) lipid emulsions on pulmonary vascular resistance (PVR) and thromboxane production, we studied three groups of newborn piglets after three days of either sow's milk (milk), or total parenteral nutrition (TPN) with either iv soy bean oil (SBO, 52% n-6 and 8% n-3 FA) or fish oil (FO, 5% n-6 and 51% n-3 FA) emulsions. At baseline, and during hypoxia at 20 min and 2 h, cardiac output (Q) was measured, PVR calculated and plasma levels of a prostacyclin metabolite (6-keto-PgF1α) and thromboxane B2 (TxB2) were measured. Fatty acid composition of the lung phospholipids was analyzed. There was an exaggerated increase in PVR and decrease in Q during prolonged hypoxia in the TPN-SBO group as compared with the other two groups. There was no difference in PVR and Q between the milk and TPN-FO groups. FA of lung phospholipids reflected the high dietary level of long chain n-3 FA in the TPN-FO group. However, no differences in plasma levels of 6-keto-PgF1α or TxB2 were found. Intravenous emulsions made from SBO reduced cardiac output and increased pulmonary vascular resistance in the hypoxic newborn piglet, whereas iv FO emulsions did not. When subjects with pulmonary hypertension are receiving TPN iv SBO may be detrimental; iv FO may be beneficial, giving similar responses as in a milk-fed subject.Key words: total parenteral nutrition, fish oil, pulmonary hypertension, lipid emulsion, fatty acids.Key words: total parenteral nutrition, fish oil, pulmonary hypertension, lipid emulsion, fatty acids.
Effect of tetramethyl pyrazine on L-type calcium channel in rat ventricular myocytes
Authors: Zou Lu-Yun , Hao Xue-Mei , Zhang Guang-Qing , Zhang Mei , Guo Ji-Hong , Liu Tai-Feng
Published: April 2011

To elucidate possible ionic mechanisms of antimyocardial ischemia and antiarrythmia of tetramethyl pyrazine (TP), we studied L-type Ca2+ currents (ICa.L) in adult rat ventricular myocytes using the whole-cell patch-clamp technique. The results showed: (i) under physiological conditions, 0.25 mmol/L TP decreased amplitude of ICa.L to 60.6% and this inhibition was increased with increasing concentration of TP. ID50 was 0.20 mmol/L. (ii) The Ca2+-antagonistic effect of TP was voltage-dependent. A marked negative shift of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) ones. (iii) The time course of inhibition during TP treatment was increased with an increase in drug concentration, and recovery from TP-induced inactivation of ICa.L was slower than in control cases. (iv) Tonic block and use-dependent block with TP treatment, which was induced by increasing the frequency of stimulation, occurred. We suggest that TP inhibits the ICa.L mainly by binding to inactivated Ca2+ channels. The high affinity of TP for the inactivated state of ICa.L may play an important role in developing therapies for pathological conditions.Key words: Tetramethyl pyrazine, L-type calcium current, rat ventricular myocytes.
Isolation of regioisomers of N-alkylprotoporphyrin IX from chick embryo liver after treatment with porphyrinogenic xenobiotics
Authors: Kobus Susan M , Wong Simon G.W , Marks Gerald S
Published: April 2011

Several porphyrinogenic xenobiotics cause mechanism-based inactivation of cytochrome P450 (P450) isozymes with concomitant formation of a mixture of four N-alkylprotoporphyrin IX (N-alkylPP) regioisomers, which have ferrochelatase inhibitory properties. To isolate the four regioisomers of N-methylprotoporphyrin IX (N-methylPP), 3,5-diethoxycarbonyl, 1-4-dihydro-2,4,6-trimethylpyridine (DDC) was administered to untreated, β-naphthoflavone-, phenobarbital-, and glutethimide-pretreated 18-day-old chick embryos. Separation of the N-methylPP regioisomers by high pressure liquid chromatography (HPLC) revealed no marked difference in the regioisomer pattern among the different treatments. After administration of griseofulvin, allylisopropylacetamide (AIA), or 1-[4-(3-acetyl-2,4,6-triemethylphenyl)-2,6-cyclohexanedionyl]-O-ethyl propionaldehyde oxime (ATMP) to untreated and glutethimide-pretreated 18-day-old chick embryos, an N-alkylPP was isolated after AIA administration only. This finding strengthened previous reports of the species specificity of N-alkylPP formation with griseofulvin and ATMP. A series of dihydropyridines, namely 4-ethylDDC, 4-hexylDDC, and 4-isobutylDDC were administered to untreated and glutethimide-pretreated 18-day-old chick embryos and hepatic N-alkylPPs were isolated and separated by HPLC into regioisomers. The regioisomer patterns obtained did not support a previous proposal of masked regions above both rings B and C in the heme moieties of the P450 isozymes responsible for N-alkylPP formation. However, the data support the hypothesis of a partially masked region above ring B alone. The regioisomer patterns were in agreement with results previously obtained in rats showing that the percentage of NCand (or) NDregioisomers in the regioisomer mixture increases as the length and bulk of the 4-alkyl substituent of a DDC analogue increase. Differences in the regioselectivity of heme N-alkylation may be due to intrinsic chemical features of DDC analogues themselves or to differences in the P450 isozymes inactivated.Key words: mechanism-based inactivation, cytochrome P450, N-alkylprotoporphyrin IX, experimental porphyria, dihydropyridine.
Bradykinin facilitates noradrenaline spillover during contraction in the canine gracilis muscle
Authors: Lavoie Julie L , Béliveau Louise
Published: April 2011

Noradrenaline spillover from skeletal muscle vascular areas increases during exercise but the underlying mechanisms are not well understood. Muscle contraction itself causes changes in many factors that could affect noradrenaline spillover. For instance, it has been reported that bradykinin is synthesized in skeletal muscle areas during contraction. Because the B2 bradykinin receptor facilitates noradrenaline spillover, it may be involved in the increase associated with contraction. In this experiment, we studied the effect of bradykinin on noradrenaline spillover in the in situ canine gracilis muscle, using the specific B2 antagonist HOE 140. The drug did not modify noradrenaline spillover at rest, but did cause a significant decrease during muscle contraction, from 558 to 181 pg·min1. As reported previously in the literature, fractional extraction of noradrenaline decreased during muscle contraction. This effect was independent of HOE 140 treatment. In light of our results, it seems that bradykinin formation during muscle contraction may play an important part in the observed increase in noradrenaline spillover but does not affect fractional extraction.Key words: skeletal muscle, fractional extraction, stimulation, HOE 140, B2 receptors.
β-Cyclodextrin inhibits the sweet taste suppressing activity of gurmarin by the formation of an inclusion complex with aromatic residues in gurmarin
Authors: Imoto Toshiaki , Sasamoto Kazushige , Ninomiya Yuzo
Published: April 2011

Our recent study in mice revealed that the inhibitory activity of gurmarin on the sweet taste responses was reduced significantly by the presence of β-cyclodextrin (β-CD). To investigate the mechanism involved in the action of β-CD, physicochemical experiments were performed on the interaction of CDs with gurmarin examining the effect of CDs on the UV absorption spectrum of gurmarin and on the elution behavior in gel filtration (or exclusion) chromatography. Among the three kinds of cyclodextrins tested, β-CD induced significant changes in the UV absorption spectrum of gurmarin that were characteristic of those found in the inclusion complex formation of tyrosine and tryptophan with β-CD. The abnormal retention behavior of gurmarin in gel filtration resulting from hydrophobic interaction with the gel matrix reverted to normal in the presence of β-CD in the elution buffer. These results suggest that the unique domain of gurmarin, in which five aromatic amino acid residues are all directed outwardly and form a hydrophobic cluster, is a possible site of interaction with the gurmarin-sensitive sweet taste receptor molecules in rodents. Key words: sweet taste, gurmarin, Gymnema sylvestre, cyclodextrin, inclusion complex.
The role of the placenta in variability of fetal exposure to cocaine and cannabinoids: A twin study
Authors: Boskovic Rada , Klein Julia , Woodland Cindy , Karaskov Tanya , Koren Gideon
Published: April 2011

There is wide variability in the reported adverse fetal effects of cocaine and cannabinoids. The causes of this variability are largely unknown. We hypothesized that variability in placental handling of drugs affect fetal exposure. We used twin pregnancies as a paradigm to address the role of the placenta in this variability. We analyzed hair or meconium samples taken from dizygotic and monozygotic twins exposed in utero to illicit drugs. Out of 12 pairs, 5 had negative levels in both twins, and seven pairs of twins had chemical evidence of fetal exposure to cocaine (n = 5) or cannabinoids (n = 2). The one known monozygotic pair of twins had almost identical levels of cocaine. In contrast, the six dizygotic pairs had large disparities in either cocaine or cannabinoid concentrations. In three of these six dizygotic pairs, levels of cocaine (n = 2) or canabinoids (n = 1) were undetectable in one twin while positive in the other. Given that twins are theoretically exposed to similar maternal drug levels, our findings suggest that the placenta may have a major role in modulating the amounts of drug reaching the fetus.Key words: cocaine, cannabinoids, placenta, twins.
Active transport of alanine by the neutral amino-acid exchanger ASCT1
Authors: Pinilla J , Barber A , Lostao M P
Published: April 2011

ASCT1 protein is a member of the glutamate transporter superfamily, which shows system ASC selectivity and properties and has been characterized as a Na+-dependent neutral amino-acid exchanger. Here, by using ASCT1-expressing oocytes, the uptake of alanine and glutamate was measured to investigate ASCT1's ability to mediate a concentrative transport of alanine, ASCT1's sodium dependence, and the influence of pH on the mutual inhibition between alanine and glutamate. Alanine uptake was measured after 30 min incubation. Kinetic analysis of the Na+dependence of alanine uptake showed an apparent K0.5(affinity constant) value for Na+of 23.1 ± 4.3 mM (mean ± SE). Concentration dependence of alanine uptake was tested at 100 and 1 mM Na+, with apparent K0.5values of 0.16 ± 0.04 and 1.8 ± 0.4 mM, respectively, at pH 7.5, and 0.21 ± 0.06 and 1.9 ± 0.3 mM at pH 6. Vmaxwas not modified between 100 and 1 mM Na+at either pH. ASCT1 actively transports alanine and accumulates it in the cytosol even when the Na+concentration in the medium was as low as 13 mM.22Na uptake studies revealed that Na+transport was stimulated by the presence of alanine in the medium. Our results demonstrate that ASCT1 is able to mediate a concentrative transport of alanine, which is Na+-dependent but not coupled to the Na+gradient.Key words: ASCT1, sodium, Xenopus laevis oocytes, concentrative transport, alanine.
THE ANTICOAGULANT AND METACHROMATIC PROPERTIES OF THE HEPARINOID G31150 IN DOGS
Authors: Jarrett Clifford L. , Jaques L. B.
Published: April 2011

The heparinoid G31150 was studied in dogs, by techniques designed originally for heparin. The compound (a breakdown product of polygalacturonic acid, methyl ester (Geigy)) has 1.3 times the metachromatic activity but only 1/10 to 1/26 the anticoagulant activity of heparin. Heparinoid G31150 could be recovered quantitatively by procedures used to extract heparin from blood. Following intravenous injections of heparinoid G31150 approximately 50% of the injected metachromatic activity was found to be excreted in the urine. By its metachromatic activity the injected heparinoid was detected in the circulation, decreasing at a constant rate over a [Formula: see text] hour period. Determinations of coagulation time indicated much less G31150 present for a much shorter time.
THE EVALUATION IN THE DOG OF A PROTEOLYTIC ENZYME DERIVED FROM ASPERGILLUS ORYZAE
Authors: Roschlau Walter H. E.
Published: April 2011

A proteolytic enzyme (Aspergillin-O) derived from Aspergillus Oryzae was studied. For this purpose arterial and venous occluding thrombi in dogs were subjected to systemic treatment with the enzyme, and the value of Aspergillin-O in thrombolytic therapy, as well as its toxic side effects and some aspects of its pharmacology are described. Lysis of occluding arterial thrombi was achieved within a few hours after the administration of enzyme preparations by single intravenous injection, and arteries remained patent during the week of post-treatment observation. The thrombolytic dose was found to vary from animal to animal, but was generally comparable in its effect to a dose of human fibrinolysin of between 250 and 300 Michigan Department of Health caseinolytic units. The variations in dose requirements and toxicity were attributed to individual protease resistance, and a dose prediction test based on this concept is described. The dose prediction test was found to make possible the safe and efficient use of the enzyme in systemic thrombolytic therapy.
A STUDY OF THE EFFECTS OF PITRESSIN AND SEROTONIN IN THE MAINTENANCE OF BLOOD PRESSURE IN THE HYPOPHYSECTOMIZED HYPOTHERMIC RAT
Authors: Hunter J. , Haist R. E.
Published: April 2011

It was shown previously that warming the exteriorized kidneys, along with the infusion of Pitressin in hypophysectomized cooled rats, gave excellent maintenance of blood pressure at low body temperatures. Infusions of saline perfusates of kidney and heart into hypophysectomized cooled rats were ineffective by themselves but, combined with the infusion of Pitressin, gave good maintenance of blood pressure at low body temperatures. Since some clotting may have occurred in blood remaining in the organs when the isolated organs were perfused it was necessary to test the effectiveness of an agent released during clotting, namely, serotonin. By itself serotonin had no effect on blood pressure in hypothermic hypophysectomized rats down to a body temperature of 20 °C, at which temperature it had a striking pressor action. When Pitressin and serotonin were infused together, the blood pressure was well maintained in hypophysectomized cooled rats down to a body temperature of 16 °C. These experiments indicate the importance of Pitressin, and the interaction of Pitressin with other factors, in maintaining blood pressure in hypothermic animals.
EFFECT OF GUANETHIDINE ON METABOLIC RESPONSE TO NORADRENALINE AND COLD RESISTANCE IN WARM-ACCLIMATED RATS
Authors: Héroux O.
Published: April 2011

Intraperitoneal administration of guanethidine for 6 weeks to 26 °C acclimated rats (5 mg every third day) resulted in an increased sensitivity to noradrenaline. The observed rise in metabolic response to a single dose of noradrenaline (2 mg/kg, intramuscular) was similar in these guanethidine-treated rats to the hone observed in cold-acclimated rats; however, their cold resistance was not changed. It is concluded that the increased sensitivity to noradrenaline of the chronically cold-exposed rats is not sufficient by itself to explain even in part their increased resistance to cold.
METABOLIC RESPONSE OF NUDE HUMAN SUBJECTS TO ACUTE EXPOSURE AT 10 °C
Authors: Girling F.
Published: April 2011

Acute exposures to cold (10 °C) for up to 90 minutes were carried out in late April and early May on 10 unclothed healthy male subjects to follow their shivering responses, oxygen consumption, skin and oral temperatures. The 10 subjects divided into two groups with markedly different responses. Group 1 showed no increase in oxygen consumption for the initial 15 minutes of exposure. After 15 minutes the oxygen consumption increased by about 45% and appeared to be coincident with shivering. Group 2 showed an immediate increase in oxygen consumption on exposure, to about 45% above control values, and shivering in this group was delayed or absent. The difference between the two groups is explained on the basis of a greater degree of acclimatization to cold in the subjects of group 2. It is suggested that the immediate increase in oxygen consumption in group 2 is triggered by a greater initial rate of heat loss in this group.
THE EFFECT OF TOLBUTAMIDE ON HEPATIC GLUCOSE-6-PHOSPHATASE ACTIVITY IN RATS PRETREATED WITH INSULIN FOR 4 WEEKS
Authors: Hawkins Rosemary D. , Haist R. E.
Published: April 2011

Rats pretreated with daily injections of insulin display, during the period immediately following cessation of injections, symptoms indicative of insulin insufficiency. During this interval, hepatic glucose-6-phosphatase levels are consistently elevated. Administration of tolbutamide (250 mg/kg body weight per os) fails to cause a depression in hepatic glucose-6-phosphatase levels in these animals, whereas, in normal rats, this agent does reduce significantly the levels of activity of this enzyme in the liver.The failure of tolbutamide to depress hepatic levels of glucose-6-phosphatase in insulin-pretreated rats in which secretion of insulin cannot be readily obtained is consistent with the hypothesis that one of the means by which tolbutamide exerts its effects is stimulation of the release of this hormone by the islets of Langerhans.
A COMPARISON OF THE METABOLIC EFFECTS OF HUMAN AND PORCINE CORTICOTROPIN IN A NORMAL HUMAN
Authors: Blair Jr. A. J. , Dyrenfurth I. , Venning E. H. , Beck J. C.
Published: April 2011

The effects of human and porcine ACTH on a human male have been compared in equivalent steroidogenic (in vitro) doses. Sodium and chloride retention were of the same order; potassium and nitrogen balances were of greater negativity during the administration of porcine ACTH. The increment of increase for the urinary 17-hydroxycorticosteroids was greater for the pig preparation but those of the urinary 17-ketosteroids and aldosterone were comparable. A transient ascorbic acid diuresis was observed with both agents and glycosuria was more marked during the use of human ACTH.
EXTRACTION AND CHEMICAL CHARACTERISTICS OF ANOREXIGENIC AND FAT-MOBILIZING SUBSTANCES FROM RAT URINE
Authors: Beaton John R. , Szlavko A. J. , Stevenson J. A. F.
Published: April 2011

An anorexigenic and fat-mobilizing substance (FMS I), extracted from the urine of fasting rats, has been further fractionated into two materials, FMS IA and FMS IB, soluble in alkaline solution or water respectively. These two fractions have been shown to be chemically distinct by thin layer chromatography, electrophoresis, and analyses for nitrogen, carbohydrate, hexosamine, phosphorus, and "cholesterol". Further, the lipolytic activities of these extracts in vitro differ and are in the order FMS IB > FMS I > FMS IA. It has been tentatively concluded that FMS I and IA contain the 17 amino acids tryptophane, phenylalanine, leucine, arginine, isoleucine, tyrosine, valine, alanine, proline, serine, histidine, glycine, aspartic acid, glutamic acid, cystine, threonine, and lysine. FMS IB appears to contain the same amino acids with the exception of valine (which is absent). These are complex substances, the precise nature of which remains to be elucidated. It appears that the anorexigenic property of FMS I is attributable to the IA component, and the fat-mobilizing property in vivo to the IB component.
ACTIVITY AND PATTERNS OF RATS FED A LOW-PROTEIN DIET AND THE EFFECTS OF SUBSEQUENT FOOD DEPRIVATION
Authors: Beaton J. R. , Feleki V. , Stevenson J. A. F.
Published: April 2011

Rats previously fed a low-protein diet (5% casein) survive deprivation of food for a shorter period than do animals fed an adequate diet (20% casein) even though this be fed in isocaloric amounts. The present investigation examined effects of feeding a low-protein diet and of subsequent survival during food deprivation under various conditions: in activity and standard cages, in temperate (23 °C) and cold (5 °C) environments. During feeding, those animals provided with the low-protein diet did not exhibit a total running activity or activity pattern markedly different than those of pair-fed controls. The results revealed that the shorter survival in cold or temperate environment after a low-protein diet is not attributable to differences in (a) total running activity or activity pattern, (b) feeding pattern, or (c) previous caloric intake and weight change. It was also noted that rats in activity cages do not eat or gain as much as rats in standard cages.
ENERGY: PROTEIN RELATIONSHIPS IN THE DIETS OF GROWING MINK
Authors: Allen Marilyn R. Pearcey , Evans E. V. , Sibbald I. R.
Published: April 2011

The apparent digestibility coefficients for energy and protein and the growth responses from weaning to the age of 28 weeks were studied in male and female standard dark mink receiving diets varying in crude protein and gross energy content. Diets containing 16% of crude protein and gross energy at levels of 4.5, 5.6, and 6.7 Cal/g of dry matter were inadequate for survival and growth of weanling mink of either sex. The protein of diets containing either 22% or 28% of crude protein was digested better by males than by females; the digestibility of protein from these rations by males was greater at 21 weeks than at 11 weeks of age, but no such effect of age was found with females. Mature body weights and body lengths of male mink increased as the ratio of apparent digestible energy (A.D.E.) to apparent digestible protein (A.D.P.) was reduced from 34 to 12 (Cal per 100 g/percent protein), the major effect occurring prior to the age of 16 weeks. The A.D.E.:A.D.P. ratios affected the performances of female mink to a lesser degree than those of male mink. Diets containing gross energy at levels below 4.9 Cal/g of dry matter did not support optimum growth of males, but gross energy levels at least as low as 4.5 Cal/g of dry matter appeared to be satisfactory for the growth of females.
CHANGES IN THE PATTERNS OF IN VITRO RESPIRATION OF KITTEN DIAPHRAGMS DURING THE FIRST FEW WEEKS AFTER BIRTH
Authors: Baum Harold , El-Khanagry Hosny A. , Moore Roland E.
Published: April 2011

The pattern of respiration in vitro of hemidiaphragms from cats aged 1 to 42 days was studied. The initial rate (i.e. [Formula: see text] in the first 30 minutes) was higher after animals had been killed traumatically than under Nembutal. The initial rate after Nembutal was indistinguishable from the steady rate (i.e. [Formula: see text] during the period 30–60 minutes) for the group killed traumatically, and both of these rates were independent of animal size. However, the initial rate (traumatic killing) and the [Formula: see text] in the presence of added succinate (whatever the method of killing) both decreased with increasing animal weight. The [Formula: see text] value in succinate was indistinguishable from that in oleate and both were higher than the initial rate. The patterns of respiration observed are discussed in terms of O2and substrate availability and of a possible carrying over of a metabolic stimulation from in vivo to in vitro after traumatic killing.
EFFECTS OF AMODIAQUIN AND QUINIDINE ON CARDIAC CONDUCTION
Authors: Kirk Bryan W. , Dresel Peter E.
Published: April 2011

The effects of the antiarrhythmia agents amodiaquin and quinidine on conduction times through the atrium and the specialized conducting tissue to the ventricular myocardium have been determined from records obtained with needle electrodes suitably placed in isolated blood perfused dog hearts. Quinidine slowed conduction through each portion of the total pathway when very low concentrations were infused but had a preferential depressant effect on atrial conduction at slightly higher concentrations. Amodiaquin slowed conduction in the atrioventricular node to a greater extent than in the other parts of the common pathway at all concentrations tested. The major effect of each drug on extra-atrial conduction occurred at the atrioventricular node and at the Purkinje–myocardial junction. Amodiaquin did not induce bigeminal rhythm in the isolated heart.
SOME EFFECTS OF INSULIN ON THE BLOOD SUGAR AND INORGANIC PHOSPHORUS LEVELS OF NORMOTHERMIC AND HYPOTHERMIC RATS
Authors: Crawford Anne L. , Haist R. E.
Published: April 2011

Blood sugar, inorganic phosphorus, and hematocrit values were measured in hypothermic and normothermic untreated rats and rats injected subcutaneously with insulin. In hypothermic rats the inorganic phosphorus levels were higher than in normothermic animals. The injection of 0.5 units of insulin per kilogram of body weight into fasted normothermic rats caused a significant fall in blood sugar level, but this rose again within 3 hours. The administration of the same amount of insulin to fasted or fed hypothermic rats (colonic temperature of 25 °C) led to a significant fall in blood sugar level, with little tendency for this to rise again at 3 or even at 6 hours. At a body temperature of 20 °C the blood sugar levels continued to fall until very low values were reached. When 0.2 units insulin/kg was injected there was very little hypoglycaemic effect in normothermic rats, but in hypothermic rats (25 °C) a hypoglycaemic effect similar to that obtained with 0.5 units was observed for the first 3 hours, but a significant return toward the initial level was evident by 6 hours. The blood inorganic phosphorus changes after the injection of insulin were not very dramatic and not greatly different in normothermic and hypothermic rats.
PREVENTION OF CUTANEOUS CALCIPHYLAXIS IN CALCIUM-DEFICIENT RATS
Authors: Jean Pierre , Desaulniers Denis
Published: April 2011

Dietary calcium is essential for the production of skin calcification in rats calciphylactically sensitized with dihydrotachysterol (DHT) and challenged with FeCl3injection, or with the mild trauma of epilation. A calcium-deficient diet delays the rise in serum calcium after the administration of DHT. A comparatively lower calcium–phosphate product at the time of challenge could explain the absence of skin calcification in these animals.
COMPARATIVE EFFECTS OF SUCROSE AND CORNSTARCH IN LOW-PROTEIN DIETS FED TO RATS EXPOSED TO COLD
Authors: Beaton J. R. , Sangster J. F.
Published: April 2011

Young male rats were fed one of three low-protein (5% casein) diets differing in the source of carbohydrate (sucrose, equal parts sucrose and cornstarch, or cornstarch) or a 20% casein (sucrose) diet at environmental temperatures of 24 °C or 5 °C. Replacement of sucrose with starch appeared to have a small but significant effect in increasing body weight gain for 15 days (but not the next 28 days) at 24 °C and also in animals exposed to cold for 28 days after a 15-day feeding period at 24 °C. In disagreement with results reported by Andik et al., cold exposure, although significantly increasing body weight gain and food intake in rats fed the 5% casein – starch diet, did not elicit a weight gain as great as that observed in 20% casein-fed animals at either 24 °C or 5 °C. The 24-hour food intake following a 24-hour fast exceeded the intake on the day before fasting on all diets for animals maintained at 5 °C but not 24 °C. The immediate ([Formula: see text] hour) and 24-hour food intakes of rats at 5 °C exceeded those of comparable dietary groups at 24 °C. At 5 °C, the 24-hour food intake, following the fast, of rats fed the 5% casein – starch diet exceeded that of the 20% casein-fed controls.
CARDIOVASCULAR REACTIVITY IN ANAEMIC DOGS
Authors: Chiong M. A. , Hatcher J. D.
Published: April 2011

Cardiovascular responses to the intravenous administration of adrenaline were measured as a means of assessing cardiovascular reactivity in intact anaesthetized dogs, before and at 3 hours and 3 days after the rapid production of anaemia by a dextran-for-blood exchange. Three types of experiments were carried out. In experiments A and B, 2.0 and 5.0 μg/kg of adrenaline (respectively) were injected intravenously before and at both periods after exchange, and the changes in arterial blood pressure were assessed. In experiment B the changes in the arterial plasma concentration of potassium and sodium were also measured. In experiment C, several cardiovascular parameters, including cardiac output (Fick method), arterial pressure, and heart rate, were measured before and at the end of a 15-minute infusion of adrenaline in a dose of 0.2 μg/kg minute. In all three experiments, evidence of a reduced cardiovascular response to adrenaline was found when the dogs were anaemic; and in experiment B the adrenaline-induced hyperkalaemia and hyponatraemia were found to be significantly reduced during anaemia.The mechanism of the hyporeactivity to adrenaline during anaemia is not clear, but may include changes in blood volume, electrolyte disturbances, and severe anoxia.
FAILURE OF GUINEA PIG ANTIBODY TO BEEF INSULIN TO NEUTRALIZE PANCREATIC AND SERUM GUINEA PIG INSULIN ACTIVITY IN VITRO
Authors: Davidson J. K. , Haist R. E.
Published: April 2011

In vitro studies of the ability of sera of guinea pigs containing antibodies to beef insulin to neutralize guinea pig insulin extracted from serum and pancreas were carried out. Glycogen synthesis by mouse hemidiaphragm was used as the biologic indicator of insulin activity. The sera were incapable of neutralizing the biologic activity of any of the samples of guinea pig insulin tested. This was true despite the fact that the antibody content of the serum was greatly in excess of the content required to neutralize a beef insulin standard completely. Some of the possible reasons for divergent findings of different investigators who have studied the problem of guinea pig insulin neutralization by sera of guinea pigs containing antibodies to beef insulin are discussed.
CARDIOVASCULAR EFFECTS OF PRONETHALOL IN THE DOG
Authors: Chiong M. A. , Binnion P. F. , Hatcher J. D.
Published: April 2011

The cardiovascular effects of an intravenous injection of pronethalol (2.5 mg/kg) and the effect of this agent on the cardiovascular changes induced by an infusion of adrenaline (0.2 μg/kg per minute) were investigated in intact anaesthetized dogs. Fifteen minutes after the administration of pronethalol, significant increases were observed in oxygen consumption, right ventricular systolic pressure, and haematocrit, and decreases in arterial blood pressure and total peripheral resistance. Arterial hypotension and a fall in stroke work were the only changes noted at 30 minutes. There was considerable variability in cardiac output, stroke volume, and heart rate but, on the average, no significant change was observed. Pretreatment with pronethalol abolished or significantly reduced the adrenaline-induced rises in cardiac output, heart rate, stroke volume, stroke work, oxygen consumption, right ventricular systolic pressure, and arterial haematocrit, and reversed the changes in diastolic arterial pressure and peripheral resistance. It is concluded that pronethalol is not devoid of sympathomimetic activity and that it effectively blocks the adrenaline responses mediated by β-receptors.
THE ROLE OF THE MOTHER IN 131I METABOLISM OF SUCKING AND WEANLING RATS
Authors: Samel M. , Caputa A.
Published: April 2011

In newborn rats the mother provokes the emptying of the urinary bladder by stimulating the perineum with her tongue. The possibility that mothers may thereby ingest the urine of their young has been studied by means of 131I on nine litters of rats aged 10 to 29 days. The results indicate that a considerable quantity of 131I administered intraperitoneally to 10- and 18-day-old rats, which were then reunited with their mothers for 4 hours, reappears in the organism of uninjected nurslings after passing through the organism of the mother. The amount of 131I transferred from injected rats into the bodies of isolated uninjected rats of the same litter decreased during the period of weaning. The observed recirculation of 131I between immature rats and their mothers in both directions may represent a saving mechanism which might include several other substances and would compensate for their loss via the milk, and suggests a new aspect of maternal–neonatal interrelationship which appears as a continuation of the state existing in utero.
A SEX DIFFERENCE IN THE TEMPERATURE RESPONSE OF RATS TO EXERCISE
Authors: Thompson G. E. , Stevenson J. A. F.
Published: April 2011

The changes of colonic and tail skin temperatures were measured in male and female rats exercised on a motor-driven treadmill at a speed of 4.6 m/minute. The pattern of changes in these temperatures was the same in the two sexes except that the females tolerated a significantly higher colonic temperature than the males before beginning to vasodilate in the tail, and, perhaps as a result, the females regulated core temperature at a significantly higher level as exercise continued. Ovariectomy or prolonged (7–14 days) treatment with progesterone (12 mg/day) resulted in the temperature response to exercise of the female approaching that of the male, but not entirely eliminating the difference.
AN INVESTIGATION OF CENTERS SUSCEPTIBLE TO MECHANICALLY AND ELECTRICALLY INDUCED AFTERDISCHARGE IN THE CAT BRAIN
Authors: Leclercq Bruno , Segal Mark
Published: April 2011

The cat's brain was mapped for centers susceptible to mechanically and electrically elicited afterdischarges. The observation that certain regions of the cortex were highly susceptible to mechanical injury by compression may be of fundamental importance in an understanding of the genesis of cortical epileptic foci. Highly electrically sensitive centers were found in the cortex, amygdala, and the hippocampus. These areas did not present a uniform sensitivity for this activity. The existence of gradients of threshold voltage between and around the sensitive centers could well explain the marked variations in threshold for afterdischarges, reported by numerous investigators. All of the highly susceptible centers in the different areas responded to similar threshold stimuli. The results, when compared with data obtained from other species, indicated that there was no reason to postulate the existence of different sensitivities between species for the afterdischarge response. The existence of highly susceptible centers might provide a basis from which the ultimate mechanisms underlying clinical epilepsy may be elucidated.
SPONTANEOUS RUNNING ACTIVITY AND TESTICULAR FUNCTION IN WHITE RATS
Authors: Smith Lorraine C. , Dugal L. P.
Published: April 2011

We have confirmed the finding of others that the spontaneous running activity recorded in standard revolving activity cages under constant conditions of light and temperature is markedly reduced by castration of male rats in early adulthood. Activity could, however, be returned to the high precastration levels by the implantation of testosterone propionate pellets which are slowly absorbed to give a continuous supply of the hormone. Testosterone pellets also inhibited the decline of activity with age in 'normal' rats.
EFFECT OF THIAZIDES ON METACORTICOID HYPERTENSION AND ON THYROID ACTIVITY OF RATS
Authors: Fregly Melvin J. , Gennaro Jr. Joseph F.
Published: April 2011

Chronic oral administration of either chlorothiazide (3.8 g/kg food) or hydrochlorothiazide (0.6 g/kg food) provides significant protection against metacorticoid hypertension induced by desoxycorticosterone trimethylacetate (post-DTMA hypertension) in rats as assessed by smaller heart weight and lower systolic blood pressure than in controls. Ratio of thyroid weight to body weight is increased by drug treatment. Both thiazides also appear to affect activity of the thyroid gland in that rate of loss of I131 is increased whereas both radioactivity of the excised thyroid gland and thyroid to serum ratio of radioactivity are reduced. Rate of oxygen consumption by chlorothiazide-treated rats is also reduced. In addition, histological appearance of the thyroid glands of both treated groups show extreme (chlorothiazide) to moderate (hydrochlorothiazide) stimulation. It is apparent that these drugs affect both size and activity of the thyroid gland at the dose levels used. It cannot be stated with certainty whether the effect of these drugs on the thyroid gland is associated with their antihypertensive property.
BIOCHEMICAL CHANGES OF THE RAT MYOCARDIUM INDUCED BY ISOPROTERENOL
Authors: Kako K.
Published: April 2011

The hearts of rats receiving two subcutaneous injections of 40 mg/kg isoproterenol on consecutive days were analyzed 24 hours after the second injection together with those of control rats receiving saline. The myocardial contents of ATP, ADP, AMP, phosphorylcreatine, lactate, and pyruvate were determined enzymatically. Glycogen, creatine, triglyceride, total cholesterol, and phospholipids were also measured.In fed as well as in rats starved for 48 hours, the myocardial ATP and creatine contents were significantly lower in the isoproterenol-treated rats than in the controls. The decrease in ATP level was observed even 48 hours after the last injection. Isoproterenol injections resulted in an increase in pyruvate content and a decrease in triglyceride content of the myocardium of fasted rats. However, the control values of these two substances also differed significantly from those found in fed controls.The total water content of the heart was higher in the isoproterenol-treated fasted rats. The blood content of the myocardium, on the other hand, was decreased in isoproterenol-treated rats.Difficulties involved in proper tissue sampling and handling, together with the importance of the observed changes, are discussed.
CHANGES IN TISSUE HISTAMINE OF GUINEA PIGS AFTER PRETREATMENT WITH HISTAMINE-RELEASING AGENTS AND ACETYLSALICYLIC ACID
Authors: Constantopoulos G. , Kovacs Eva M. , Melville K. I.
Published: April 2011

Guinea pigs were treated with compound 48/80 and cortisone for 14 days. Seven days after the last dose the animals were killed and their organs extracted for histamine. All organs examined showed a decrease in histamine, which was greatest in the lung, liver, skin, and heart, in which the levels of histamine were significantly lowered (49.3%, 42.3%, 39.5%, and 32.7% respectively) compared to control values. When tissues were extracted 24 hours after the last dose, the reduction in histamine contents was less. Treatment with compound 48/80 alone for 3 days did not release histamine from guinea pig organs. The administration of 48/80 for 2 weeks reduced the histamine content of the lung by 18.2% and that of the small intestine by 10.7%. This reduction was sustained for at least 7 days, at which time histamine content of the ear was also reduced by 40.2%. Octylamine given for 10 days reduced the histamine content of lung, ear, and small intestine by 34.9%, 28.8%, and.18% respectively. Treatment for 21 days with acetylsalicylic acid increased histamine content of small intestine, ear, and lung by 44.1%, 16.4%, and 10.9% respectively.
EFFECTS OF DIELDRIN ON THE METABOLISM OF VITAMIN A AND CAROTENE IN THE RAT
Authors: Phillips W. E. J.
Published: April 2011

The rate of decrease of liver stores of vitamin A and the utilization of dietary or orally administered carotene and vitamin A have been studied in the rat following the feeding of 0 to 20 p.p.m. dieldrin in the diet. Dieldrin produced no abnormal effects on these conditions. Subacute toxic doses of dieldrin administered orally similarly did not directly influence the blood or liver levels of vitamin A. The observed decreases of liver vitamin A following ingestion of high doses of dieldrin are not a direct effect of dieldrin per se but secondary because of inanition.