bluuebunny/crossref_metadata_2025 huggingface dataset:
EDHF mediates the relaxation of stretched canine femoral arteries to acetylcholine
Authors: Woodley N , Meunier R L , Barclay J K
Published: April 2011

To test the hypothesis that mechanically stretched arteries relax to endothelium-derived vasodilators, we challenged endothelium-intact dog femoral artery rings stretched from 1 to 16 g total initial tension (active force and passive elastic) with 106 M acetylcholine (ACh), an endothelium-dependent dilator. The relaxation to 106 M sodium nitroprusside (SNP), an endothelium-independent dilator, increased with the total initial tension. The relaxation to ACh averaged approximately 65% of the relaxation to SNP at total initial tensions of 4 to 16 g. To determine the nature of the endothelial-derived products involved, we compared the ACh-induced relaxation of stretched rings (6.5 ± 0.2 g total initial tension) with rings chemically contracted with phenylephrine (Phe, 107 to 105 M) (6.5 ± 0.3 g total initial tension). ACh-induced relaxation was evaluated before and after the inhibition of the synthesis of eicosanoids [cyclooxygenase (105 M indomethacin) and lipoxygenase (105 M nordihydroguariaretic acid)] and nitric oxide [nitric oxide synthase (105 M Nw-nitro-L-arginine)]. The contribution of endothelium-derived hyperpolarizing factor (EDHF) was identified by blocking calcium-activated potassium channels (108 M iberiotoxin). SNP (106 M) relaxed stretched rings by 1.7 ± 0.1 g and chemically-activated rings by 4.8 ± 0.2 g. ACh relaxed stretched rings to 73 ± 3% of the SNP relaxation and this was only attenuated in the presence of iberiotoxin. ACh relaxed Phe-activated rings to 60 ± 3% of the SNP relaxation. This relaxation was attenuated by inhibition of the synthesis of nitric oxide and (or) eicosanoids. Therefore, ACh relaxed stretched rings through the release of EDHF whereas the relaxation of chemically activated rings to ACh involved multiple endothelium-derived vasodilators.Key words: endothelium-derived relaxing factor (EDRF), endothelium-derived hyperpolarizing factor (EDHF), arachidonic acid metabolites.
Bethanechol and N-acetylcysteine mimic feeding signals and reverse insulin resistance in fasted and sucrose-induced diabetic rats
Authors: Lautt W. Wayne , Schafer Joshua , Macedo M. Paula , Legare Dallas J.
Published: April 2011

Meal-induced insulin sensitization (MIS) is explained by the HISS (hepatic insulin sensitizing substance) hypothesis. In the presence of two “feeding signals,” a pulse of insulin results in the release of HISS from the liver. HISS acts selectively on skeletal muscle and doubles the response to insulin. HISS is not released in the fasted state or in the sucrose-supplemented diabetes model. We tested the hypothesis that provision of both feeding signals allows insulin to cause HISS release in both the normal fasted and the diabetic model. The dynamic response to insulin (50 mU/kg over 5 min) was quantified using the rapid insulin sensitivity test (RIST). Gastric injection of a liquid test meal or i.v. administration of N-acetylcysteine in 24 h fasted rats raised hepatic glutathione to a similar degree (by 46%–47%). Hepatic denervation in fed rats eliminated the parasympathetic signal and eliminated MIS, and bethanechol completely restored MIS. Both compounds administered together allowed insulin to stimulate HISS release in 24 h fasted rats and in a diabetic model (9-week, 35% liquid sucrose supplement). Neither was effective alone. Both “feeding signals” are necessary and sufficient for insulin to stimulate HISS release.
THE METABOLISM OF VINCA ALKALOIDS: PART I. PREPARATION OF TRITIATED VINBLASTINE; THE RATE OF URINARY EXCRETION OF RADIOACTIVITY BY RATS RECEIVING THE COMPOUND
Authors: Beer C. T. , Wilson M. L. , Bell J.
Published: April 2011

The preparation of tritium-labelled vinblastine by the Wilzbach irradiation method is described. Tritiated dihydrovinblastine was concurrently formed and could not be detected or separated from tritiated vinblastine by previously available methods. It is now found that tritiated vinblastine can be freed from the contaminating dihydro compound by chromatography on cellulose phosphate. The rate of urinary excretion of radioactivity by rats given injections of the purified alkaloid has been studied. About 5% of the dose radioactivity is excreted in the urine collected in the 12 hour period after injection; thereafter only very minor amounts of radioactivity are eliminated by this route.
THE EFFECT OF RESERPINE ON THE SENSITIVITY OF RATS TO INSULIN AND TOLBUTAMIDE
Authors: Hawkins Rosemary D. , Crawford Anne L. , Haist R. E.
Published: April 2011

A single dose of reserpine (1 mg/kg body weight, injected subcutaneously) induced hyperglycaemia which persisted for at least 6 hours in rats kept in slings, but no significant alteration in the level of blood sugar was observed in free-running rats. The administration of a single dose of reserpine to unrestrained rats 3 hours prior to a test dose of insulin (0.5 units/kg body weight intramuscularly) or of tolbutamide (125 mg/kg per os) resulted in a decrease in the sensitivity of the animals to the hypoglycaemic action of these two compounds. Pretreatment with reserpine (1 mg/kg for 2 days) resulted in a failure of a single dose (0.5 mg/kg) of this compound to elevate blood glucose levels, in restrained rats, but such reserpine pretreated animals displayed a decreased hypoglycaemic response to a test dose of insulin.The hyperglycaemia observed in restrained rats following the injection of a single dose of reserpine was still observed in animals from which the pancreas had been completely removed, indicating that the change in blood glucose level in response to reserpine in these animals was not dependent on the presence of a pancreatic factor.
EXPERIMENTAL INVESTIGATION OF POSTSTENOTIC DILATATION IN ISOLATED ARTERIES
Authors: Roach Margot R. , Harvey Kenneth
Published: April 2011

Isolated human and dog iliac arteries were mounted in a double-chambered plethysmograph and perfused with merthiolate solution. Various degrees of stenosis were produced by plastic rings. Only arteries with moderate stenoses (i.e. those that produced a distal thrill and bruit) developed poststenotic dilatation, but all of them did. The dilatation usually started within 5 minutes, progressed rapidly for 20 to 30 minutes, and then more slowly for up to 3 days. Pressure–volume measurements showed that the dilated segment was more distensible than normal.
FIBRINOLYTIC ACTION OF RESERPINE IN RATS
Authors: Ashwin J. G. , Coughlin W. R.
Published: April 2011

The plasma fibrinolytic activity in rats was measured by the euglobulin clot lysis time technique after injection of reserpine, serotonin, epsilon-aminocaproic acid, and UML-491. Fibrinolytic activity was increased by reserpine and serotonin, the extent depending on the dosage and route of administration. With serotonin, clot lysis time returned to normal after 6–12 hours. With reserpine, this occurred after 4 days. The antifibrinoiysin E-ACA was able to reduce fibrinolytic activity for more than 24 hours, whether given alone or with reserpine or serotonin. The antiserotonin UML-491 had a paradoxical fibrinolytic enhancing action that lasted for several hours alone, or given with serotonin it increased the fibrinolytic effect of serotonin.
THE INFLUENCE OF pH ON THE HYDROLYSIS OF BENZOYLCHOLINE BY PSEUDOCHOLINESTERASE OF HUMAN PLASMA
Authors: Kalow W.
Published: April 2011

The study was performed with an automatic titrator and purified human pseudocholinesterase prepared from pooled plasma. The data obtained are compatible with the assumption that each enzyme molecule contains two binding sites for benzoylcholine which are unlike in their dependence on pH. Michaelis constants and maximum hydrolysis velocities were derived for each of the two binding sites, and acid–base dissociation constants of the enzyme substrate complexes were estimated.
THE NORMAL BLOOD SUGAR OF THE TOADFISH
Authors: Nace Paul Foley , Moule Margaret L. , Schuh Joseph E.
Published: April 2011

The blood sugar level in normal toadfish was determined by modified Folin and glucose oxidase methods. More than 1800 fish were used during five summers and one winter. In January and April, the blood sugar level was more than 100 mg% by both methods. The summer level was approximately 33 mg% (Folin) and 20 mg% (glucose oxidase). Significant daily fluctuations in the blood sugar level were found during the spawning period. The daily standard deviation was usually less than 10 mg%. The results suggest that the blood sugar is under a more efficient control system than was expected.
ACUTE EXPOSURE OF HUMAN SUBJECTS TO AN AMBIENT TEMPERATURE OF 10 °C
Authors: Hurley D. A. , Topliff E. D. L. , Girling F.
Published: April 2011

Acute exposures to cold (10 °C) for 1 hour were carried out in early April on five unclothed healthy male subjects to follow their shivering responses, oxygen consumption, ventilation, skin and oral temperatures. Exposure to the cold resulted in immediate (within 5 minutes) and sustained increases in oxygen consumption, ventilation, and heat production. These subjects did not show generalized shivering, however, until after 30 minutes of exposure, even though short bursts of shivering were noted before this time. The immediate increase in heat production without shivering is indicative of a non-shivering thermogenesis which may be the result of cold-acclimatization in these subjects. Seasonal acclimatization would be maximal at the time of year during which the experiments were carried out.
HEMODYNAMICS DURING THE CHRONIC STAGE OF MYOCARDIAL DAMAGE CAUSED BY ISOPROTERENOL
Authors: Beznak Margaret , Hacker P.
Published: April 2011

Cardiovascular measurements were performed in rats 3–4 days, 1 week, 2 weeks, 5–6 weeks, and 4–5 months after the subcutaneous injection of 40 mg/kg isoproterenol on two consecutive days. Up to 1 week after the injections severe histological damage of the myocardium was accompanied by cardiac enlargement and impaired function: blood pressure, cardiac output and work were in the normal range under basal conditions but the maximum cardiac output and work measured during infusion of polyvinylpyrrolidone into the right side of the heart were well below normal. During the following weeks histological repair took place and the cardiovascular parameters measured were not different from those found in normal rats. This period was followed by a third stage which occurred without further interference with the heart. It consisted of thinning of the ventricular wall and aneurysm formation. All cardiovascular values (maximum and basal as well) were below normal without development of cardiac enlargement.
SOME BEHAVIORAL EFFECTS OF STIMULATION OF THE CAUDATE NUCLEUS IN UNRESTRAINED CATS
Authors: McLennan H. , Emmons P. R. , Plummer P. M.
Published: April 2011

The effects of stimulation of the caudate nuclei of completely unrestrained cats are described. The responses observed depend critically upon the frequency of stimulation; unilateral caudate stimulation showed "arrest" of movement at the lowest frequencies, which gave place to a contraversive turning and circling as the frequency was raised. Bilateral stimulation gave only "arrest" at all frequencies tested, but the animals could be induced to circle to either side by a sudden distracting stimulus. The possible pathways involved in these responses are considered, and the conclusion is reached that "arrest" and circling depend upon two different neural routes.
THE INTERCONNECTION BETWEEN ACTIVE TRANSPORT AND CONTRACTURE IN UTERINE TISSUES
Authors: Daniel E. E.
Published: April 2011

A study of the effects of several procedures known to interfere with active transport in rat, rabbit, and cat uterine muscle has revealed certain differences between muscles and between inhibitory procedures. Ouabain, fluoride, and sudden cooling caused an initial contracture followed by subsequent loss of contractility in circumstances in which they inhibit active transport. Removal of external potassium increased and subsequently decreased isometric contractions at 37 °C of rat and cat uterine segments, and in most of rat uterine horns caused contracture at 24 °C followed by relaxation and loss of contractility. The parallelism between the initial contracture and inhibition of active transport extends to the necessity for a concentration of 10−4 M to 10−3 M ouabain for initiation of both in rat uteri in contrast to the effectiveness of 10−7 M to 10−5 M in rabbit and cat uteri. The contracture induced by ouabain in rat uteri was potentiated by a decrease in external potassium and prevented by an increase. Removal of the glucose from the medium for 1 to 2 minutes potentiated both ouabain and potassium depletion contractures, but did not significantly increase potassium loss. Lower concentrations of NaF caused contracture in the absence of glucose. The contractures induced by NaF and by cold were obtained in uteri depolarized by K2SO4 Ringer solution and none were prevented by selective antagonists to acetylcholine, adrenaline, histamine, or serotonin. All the procedures producing contracture were ineffective in uteri depleted of calcium. All are known to interfere with the activity of the Mg- and Na + K-activated membrane ATPase believed to be involved in active transport. Therefore, it is proposed that inhibition of this enzyme in uteri causes contracture. In view of other work, this is presumed to occur by failure of active extrusion or failure of binding of calcium at the cell surface leading to a net calcium influx. The potentiation of contractures by removal of glucose occurs too rapidly to derive from glucose or glycogen depletion and is attributed to interaction between glucose transport and cation transport mechanisms.In contrast to ouabain, fluoride, potassium depletion, and cold, iodoacetate and dinitrophenol inhibit active transport and contractility in uterine muscle without causing an initial contracture. It is proposed that these substances act either by decreasing energy supply or by acting at a non-membrane site different from that at which substances causing contracture act. Cyanide was less effective as an inhibitor of either process, and oxidative metabolism is presumed not to be essential for energy supply in these tissues. In general, the loss of ability of uterine muscle to contract on chemical stimulation was directly related to the extent of potassium depletion. Both potassium depletion and loss of contractility were attributed to decreased energy supply.Ouabain in concentrations insufficient to cause contracture or potassium loss in rat uteri prevented rhythmic activity.
URINARY EXCRETION OF Δ5-PREGNENE-3β,17α,20α-TRIOL IN NORMAL SUBJECTS AND HYPERTENSIVE PATIENTS
Authors: Nowaczynski Wojciech , koiw Erich , Genest Jacques
Published: April 2011

A study of urinary excretion of Δ5-pregnenetriol was made in normal subjects and hypertensive patients. Using a procedure previously described by us, the mean excretion of this steroid showed a statistically significant (P < 0.001) mean decrease in groups of patients with essential, renal, and malignant hypertension as compared to normal subjects.
THE HUMORAL REGULATION OF ERYTHROPOIESIS AND METABOLISM DURING RECOVERY FROM THE RAPID PRODUCTION OF ANAEMIA IN THE DOG
Authors: Jennings Donald B. , Hatcher J. Donald
Published: April 2011

The levels of erythropoietin and metabolic stimulating factor(s) were assayed in the plasma of dogs at 1 and 3 hours and at 2, 3, 4, 6–7, and 8–9 days after the rapid production of anaemia by dextran-for-blood exchange. The assay results were considered in relation to the reticulocyte response and oxygen consumption of the anaemic dogs over this same period.An increase in erythropoietin was first detected at 2 days and reached a maximum by 4 days after exchange. The level of erythropoietin was falling by 6–7 days and reached control levels by 8–9 days. An increase in reticulocyte level in anaemic dogs did not occur until 3–4 days and was maximal at 8–9 days.The metabolic stimulating activity of the plasma tended to parallel the changes in level of erythropoietin except at 3 hours when there was a considerable increase in metabolic activity although there was a normal level of erythropoietin. Protein-bound iodine in plasma was decreased following dextran-for-blood exchange. The oxygen consumption of the anaemic dog was below control levels at 1 and 3 hours, but subsequently above control levels at 4 to 9 days.The changes in erythropoietin and metabolic stimulating factor were somewhat similar to the change in level of a cardiotonic agent previously found in the blood of dogs during recovery from anaemia.
ACTION OF VARIOUS DAMAGING AGENTS ON MYOCARDIAL POTASSIUM
Authors: Prioreschi P. , Gabbiani G.
Published: April 2011

The experiments described show that certain damaging procedures (bone fractures, forced muscular exercise, spinal cord section, forced immobilization) increase the level of potassium in the myocardium in rats, whereas others (hemorrhage, formalin injection, fasting) are ineffective in this respect. The rise in K concentration in the heart after forced restraint is not inhibited by adrenalectomy or hypophysectomy. These observations and the fact that there is no correlation between the damaging effect of the various procedures and their ability to increase the potassium content of the heart suggest the possibility that the phenomenon is not related to nonspecific stress but to the specific experimental procedures. If the animals are immobilized 17 hours every day for 8 days, the last period of restraint is ineffective in raising the potassium concentration in the heart.
TISSUE ENZYME RESPONSE TO COLD AND TO HYPERPHAGIA IN THE RAT
Authors: Beaton John R. , Feleki V.
Published: April 2011

In rats exposed to cold (5 °C) for 14 days the activities of liver arginase, alanine-transaminase, and glucose-6-phosphatase and of kidney phosphate-activated glutaminase were increased. In animals with a comparable hyperphagia due to bilateral ablation of the ventromedial region of the hypothalamus there was a smaller although significant increase in activity of kidney glutaminase but, in contrast to the effect of cold exposure, there was a significant decrease of liver alanine-transaminase activity and no apparent effect upon the activities of liver arginase or glucose-6-phosphatase. It is concluded that changes of enzyme activities in cold-exposed rats are not simply an adaptation to the increased nutrient flow consequent upon the hyperphagia induced.
ALTERATION OF THE ACETYLATION OF SULFONAMIDES BY PROTEIN BINDING, SULFINPYRAZONE, AND SURAMIN
Authors: Anton Aaron H. , Boyle John J.
Published: April 2011

The following observations resulted from the studies: (1) bovine albumin interfered with the acetylation of sulfamethoxypyridazine. Apparently this was due to the binding of the sulfonamide to the protein since a similar effect was not observed with bovine globulin to which this sulfonamide was not bound. Furthermore, neither protein affected the acetylation of sulfanilamide whose binding to albumin was much less than that of sulfamethoxypyridazine; (2) in the presence of albumin, but not globulin, 2–25 times more of sulfinpyrazone and suramin, respectively, was required to inhibit the acetylation of sulfanilamide to the same extent as in the absence of the protein; (3) there appeared to be no consistent correlation among a number of sulfonamides between their binding to protein, "lipid solubility," pKa, and acetylation.
DIFFERENTIAL EFFECTS OF SOME PHENOTHIAZINE DERIVATIVES AGAINST CALCIUM-INDUCED VENTRICULAR ARRHYTHMIAS IN THE ISOLATED RABBIT HEART
Authors: Beaulnes A. , Lavallee M.
Published: April 2011

This paper deals with the effects of five phenothiazine derivatives and quinidine against ventricular fibrillation induced in the isolated rabbit heart by small amounts of calcium chloride. Chlorpromazine and promethazine were more potent than quinidine in raising the calcium threshold for fibrillation. On the other hand, prochlorperazine and diethazine exerted biphasic effects: small concentrations increased the sensitivity of the heart to calcium chloride or induced fibrillation without calcium; higher concentrations had antifibrillatory effects and markedly depressed atrioventricular conduction. Thioproperazine was profibrillatory at all concentrations tested.
BENZYLPENICILLIN TOXICITY IN ANIMALS ON A SYNTHETIC HIGH SUCROSE DIET
Authors: Boyd E. M. , Mulrooney D. A. , Pitman C. A. , Abel M.
Published: April 2011

Mice became more susceptible to the lethal effects of a single dose of benzyl-penicillin (penicillin G) given orally or subcutaneously after they had been fed a synthetic diet deficient in pantothenic acid for 2 weeks. Rats developed a fulminating reaction with 50% deaths within 1 week when placed upon the same diet and given a daily dose of benzylpenicillin which, over 100 days, killed 50% of controls on fox chow. The syndrome was not due to absence of pantothenic acid, since it was not altered in mice or rats by supplementation with pantothenate, nor to absence of cellulose, nor to formation on standing of toxic products in the synthetic diet. The diet contained 64% sucrose, an amount equivalent to 40 g of sucrose eaten by a rat per kg body weight per day. When this dose of sucrose was given orally at one administration, it killed over 50% of the rats. Feeding the high sucrose synthetic diet to rats for 1 month increased the reaction to subsequent daily benzylpenicillin administration. Daily administration of benzylpenicillin for 1 month to rats on fox chow, however, reduced their susceptibility when they were transferred to the synthetic diet. The results were interpreted as indicating that the reaction was due mainly to the large amount of sucrose in the synthetic diet. Change in the intestinal flora, induced by administration of benzylpenicillin, appeared to be a secondary factor.
HORMONAL HYPERTENSION RESULTING FROM PITUITARY IMBALANCE
Authors: Hunter John , Haist R. E.
Published: April 2011

The removal of the posterior part of the pituitary gland in the rat leads to an elevation in blood pressure. The production of an anterior–posterior pituitary imbalance in hypophysectomized animals by the administration of certain hormones of target glands influenced by the anterior pituitary (thyroxine, testosterone, cortisone (TTC)) also produces an increase in mean arterial blood pressure. In the intact animal, too, the administration of the hormones of the target organs (TTC) will lead to an elevation of blood pressure, and 1 week after the cessation of this treatment the blood pressure is as high or higher than at the end of the administration period. Administration of anterior pituitary hormones TSH, LH, and ACTH both in hypophysectomized and in intact rats also produced elevations in blood pressure. In two female dogs, administration of pituitary target-organ hormones (TTC) consistently produced an elevation of blood pressure associated with a direct effect of the injected hormones, followed by a depression of blood pressure below previous resting values after hormone withdrawal, presumably because of an associated inhibition of anterior pituitary effects. When certain hormones of the posterior pituitary gland are administered along with TTC, in both hypophysectomized and intact rats, the blood pressure elevation is not as great as with TTC alone, though, by themselves, the posterior pituitary factors caused some elevation in blood pressure. It is concluded that an imbalance between the influences of the anterior and posterior parts of the pituitary gland can lead to a significant elevation in blood pressure. It seems likely that, depending on the dose, the effects observed after the injection of the agent is discontinued may be due to persistence of the action of the agent or, in some instances, to inhibition of the activity of part of the pituitary gland.
LIPID METABOLISM IN WARM-ACCLIMATED AND COLD-ACCLIMATED RATS EXPOSED TO COLD
Authors: Himms-Hagen Jean
Published: April 2011

The turnover of triglycerides and phospholipids of various tissues was studied in warm-acclimated and cold-acclimated rats, exposed to either a cold or a warm environment, by injecting glucose-U-C14intraperitoneally and measuring its incorporation into glycerol, glycerophosphate, and fatty acid portions of triglycerides and phospholipids at various times after the injection. The incorporation of glucose carbon into brown (interscapular) adipose tissue lipids (principally into glyceride glycerol) was 10 to 50 times greater in cold-acclimated rats in the cold than in warm-acclimated rats in the warm. The results are interpreted to indicate a great acceleration of the triglyceride cycle (triglyceride hydrolysis and resynthesis with concomitant ADP formation, the latter occasioning an increase in the activity of the electron transport system) in brown adipose tissue of cold-acclimated rats in the cold. Other possible interpretations are discussed. This acceleration was not observed in cold-acclimated rats in the warm or in warm-acclimated rats in the cold. No evidence was obtained for acceleration of triglyceride cycle in liver, heart, skeletal muscle, or white (epididymal) adipose tissue. The hypothesis is advanced that acceleration of the triglyceride cycle of brown adipose tissue is a major mechanism of nonshivering thermogenesis in cold-acclimated rats; such a mechanism is known to be under the control of the sympathetic nervous system and is consistent with the requirement that non-shivering thermogenesis can be switched on and off in response to changes in the environmental temperature.
PULMONARY AND CENTRAL NERVOUS SYSTEM DAMAGE IN RATS EXPOSED TO HYPERBARIC OXYGEN AND PROTECTION THEREFROM BY GAMMA-AMINOBUTYRIC ACID
Authors: Wood J. D. , Stacey N. E. , Watson W. J.
Published: April 2011

Male Wistar rats were exposed to oxygen at 6 atmospheres absolute pressure for periods of 30 and 40 minutes and the effect of the intraperitoneal administration of γ-aminobutyric acid (GABA) (20 mmoles/kg) and glucose (15 mmoles/kg) on the toxic effects of OHP was studied. GABA protected the animals against both gross lung damage and convulsions, but glucose was without effect. Since the accumulation of fluid in the peritoneal cavity was similar for GABA and glucose injections, it would appear that the protective action of GABA was not due to this influx of fluid into the peritoneal cavity brought about by the injected material. All animals having gross pulmonary pathology had suffered severe seizures during the exposure to OHP, but severe convulsions can occur without the incidence of pulmonary pathology. The significance of these observations is discussed.
THE EFFECTS OF MEPROBAMATE ON PHYSIOLOGICAL RESPONSES TO COLD
Authors: Iampietro P. F. , Fiorica V. , Dille R. , Higgins E. A.
Published: April 2011

Meprobamate (800 mg) depresses both respiratory and cardiovascular responses of men during exposure to neutral (80 °F, 26.7 °C) and cold (50 °F, 10.0 °C) environments. The inhibition of these responses is most severe during exposure to cold when the usual compensatory increases elicited by this stress are minimized. Drug-treated subjects effect only small increases in systolic and diastolic pressures during cold exposure and virtually no change in heart and respiratory rates. Although rectal temperatures of both drug and placebo groups decrease uniformly during exposure to a neutral environment, the subsequent increase stimulated by cold exposure is depressed in meprobamate-treated subjects. No differences in the hematocrit increase induced by cold exposure were detected between drug and placebo groups.
INFLUENCE OF PERIODICITY OF EATING ON ADIPOSE TISSUE METABOLISM IN THE RAT
Authors: Leveille G. A. , Hanson R. W.
Published: April 2011

The effects of meal eating (a single 2-hour meal per day) on carbohydrate and lipid metabolism were studied in rats. Food consumption was greater in rats fed ad libitum (nibblers); however, the rate of gain was similar for both groups after an initial weight loss for the meal eaters. Isolated adipose tissue from meal eaters converted more glucose to CO2, fatty acids, nonsaponifiable lipids, and glycogen than did tissue from nibbling animals. Acetate incorporation into fatty acids was also higher in adipose tissue from meal eaters. A higher level of pentose phosphate pathway activity in adipose tissue was indicated for meal-eating rats.Refeeding for up to 2 hours after a 22-hour fast resulted in increased lipogenesis in adipose tissue from meal eaters. Total oxidized pyridine nucleotide coenzyme (NAD–NADP) levels and the rate of glucose oxidation to CO2in rat epididymal fat pads were found to decrease during the first 30 minutes of refeeding in meal eaters. Changes noted in metabolic pattern induced by refeeding were apparently not due to de novo enzyme synthesis. The significance of the adaptive changes noted is discussed.
GLYCOGEN SYNTHESIS IN MOUSE HEMIDIAPHRAGMS AFTER BRIEF CONTACT WITH INSULIN
Authors: Wardlaw A. C. , Weidinger Helen J.
Published: April 2011

Evidence that insulin binds rapidly to mouse hemidiaphragms in vitro was obtained by exposing the tissues briefly to 5 milliunits insulin/ml, then washing and incubating them (in parallel with control tissues) in a glucose-containing medium to detect augmentation of glycogen synthesis. The concentration of insulin required for maximum augmentation after a 5-minute exposure at 2–4 °C was about 15 munits/ml, which is 10 times higher than the level giving maximum effect when insulin is present throughout the period of 37 °C incubation. Ten minutes' exposure gave results which were not significantly different from those obtained with 30 seconds' exposure.Binding of insulin was apparently unaffected by temperature, for treatment of tissues at 2–4 °C gave the same augmentation as exposure at 37 °C. Specific ions did not seem to be required in insulin binding, since the same degree of stimulation was observed with insulin in 0.15 M NaCl as in the more complex medium AB. Insulin binding was not inhibited by raising the ionic strength from 0.15 to 1.0. Binding was, however, affected by pH, being highest at pH 3.6, somewhat less at pH 7.2, and still less at 10.9. These findings, in general, confirm the previous studies of Stadie et al. (Am. J. Med. Sci. 218, 265 (1949)) with rat diaphragm except that we obtained significant binding with a much lower concentration of insulin than used by these authors. In addition, we found that insulin once bound to the diaphragm was only partially neutralizable by excess of an avid anti-insulin serum.
THE ELECTRICAL ACTIVITY OF THE AMYGDALA, AND ITS RELATIONSHIP TO THAT OF THE OLFACTORY BULB
Authors: McLennan H. , Graystone P.
Published: April 2011

The electrical activities of the amygdala and olfactory bulb have been recorded from unrestrained cats with the aid of a telemetering device, and the frequency spectra of the records determined. In alert animals the signal from both structures was characterized by a strong 40 c.p.s. component; this became less obvious as attentiveness declined, and in natural sleep was replaced by lower-frequency activity. The 40-c.p.s. bursts appeared to be generated in the amygdala and thence transmitted to the bulb. In lightly anesthetized animals a dissociation in activity between the two structures was noted; the amygdaloid record resembled that of natural sleep while the bulb showed a fast rhythm. The response to an olfactory stimulus depended upon the alertness of the cat. If it was fully alert, the 40 c.p.s. component was suppressed during olfaction, but if inattentive it was accentuated. It is suggested that the 40-c.p.s. bursts represent the operation of a gated system scanning for an olfactory input.
CARDIAC PERFORMANCE IN HEART–LUNG PREPARATIONS OF RATS WITH EXPERIMENTAL CARDIAC HYPERTROPHY
Authors: Korecky B. , Beznak M. , Korecka M.
Published: April 2011

Heart-lung preparations (h.l.p.) were made in normal rats and in rats with cardiac hypertrophy produced by aortic constriction, thyroxine treatment, or chronic anemia. In the h.l.p., arterial pressure was kept constant at 100 mm Hg, and maximum cardiac output (m.c.o.) was measured by stepwise increase in the inflow of blood until no further rise in cardiac output occurred. The m.c.o. of enlarged hearts was above normal, but not if it was expressed per gram of left ventricle weight. This latter value was not above normal in any of the enlarged hearts, contrary to earlier findings in whole animals. In fact, in one group of severely anemic rats it was significantly below normal.
EFFECTS OF SPREADING CORTICAL DEPRESSION ON CARDIAC AND SOMATOMOTOR CONDITIONED RESPONSES
Authors: Mogenson G. J. , Peterson R. J.
Published: April 2011

Spreading cortical depression (s.c.d.), elicited by the direct application of potassium chloride to the dura of the rat brain, has been reported to disturb motor functions and learning. In most previous studies these two effects have been confounded. A conditioned response (c.r.) in heart rate was employed in the present investigation in an attempt to separate the effects of s.c.d. on neural integrative and associative processes from the effects on motor performance.The typical cardiac c.r. was acceleration of heart rate (h.r.) during the conditioning stimulus (c.s.) followed by a secondary acceleration after the c.s. terminated. Spreading cortical depression did not alter the initial cardiac acceleration observed during the c.s. although somatomotor (shuttle box avoidance) c.r.'s were almost completely eliminated by it. The second component of the cardiac c.r., h.r. acceleration after the c.s. had terminated, was not observed during s.c.d. Apparently this second component is more easily affected by s.c.d. because it is not under direct sensory control and is therefore dependent upon memory processes. It is concluded that s.c.d. produces a decrement in spontaneous or operant behavior but has little or no influence on environmentally triggered or involuntary behavior.
FACTORS INFLUENCING THE EXCRETION OF A FAT-MOBILIZING SUBSTANCE IN THE URINE OF RATS
Authors: Beaton J. R. , Szlavko A. J. , Stevenson J. A. F.
Published: April 2011

The effect of various factors on excretion of a lipid-mobilizing activity in FMS IA (anorexigenic) and in FMS IB (fat-mobilizing) by the fasting rat has been investigated. During fasting, the greatest excretion of such activity in FMS IA and FMS IB occurred in the first 24 hours and diminished thereafter up to 72 hours; and the specific activity of FMS IB was greatest in the first 24 hours whereas that of FMS IA was constant throughout. The hypothalamicobese rat excretes FMS IA and FMS IB in greater than normal amounts. The alloxan-diabetic rat excretes less total activity of FMS IA and IB than do control animals. Young male rats excrete greater amounts of FMS IB, but not of FMS IA, than do adult rats, the greatest excretion per 100 g body weight being observed at approximately 37 days of age. At 27 days of age (prepuberty), male rats excreted a greater total activity of FMS IB but not of FMS IA than did female rats. At 90 days of age (post-puberty), there was no apparent sex difference in the amount of total activity of FMS IB excreted per rat, but when expressed per 100 g body weight, females excreted more FMS IB than did males.
OBSERVATIONS ON THE LIPOLYTIC ACTION IN VITRO OF A FAT-MOBILIZING SUBSTANCE EXTRACTED FROM URINE OF FASTING RATS
Authors: Beaton John R. , Szlavko A. J. , Stevenson J. A. F.
Published: April 2011

An investigation has been carried out of factors in the lipolytic response of adipose tissue to a fat-mobilizing substance (FMS IB) extracted from the urine of fasting rats. Response was increased when rats were exposed to cold prior to removal of adipose tissue and was decreased in adipose tissue of rats rendered hyperphagic and obese by bilateral electrolytic ablation of the ventromedial region of the hypothalamus. These observations in vitro are consistent with observations on fat catabolism or storage in vivo after cold exposure and in hypothalamic hyperphagia.Previous feeding of a high-protein diet inhibited lipolytic response in vitro of adipose tissue to both FMS IB and adrenaline; previous feeding of a noncarbohydrate high-fat diet also inhibited lipolytic response to FMS IB but not to adrenaline. Of the adipose tissues tested, lipolytic response to FMS IB was in the order epididymal > perinephric > omentum. There was no sex difference in the response of adipose tissue; the response of adipose tissue of the young male rat was considerably less than that of the adult male rat. Adipose tissue of fasted rats was much more responsive to FMS IB than was that of fed rats. This response could be almost completely abolished by the addition of glucose (180 mg/100 ml) to the incubating medium; lesser concentrations of glucose had a smaller inhibitory effect. A linear lipolytic response of adipose tissue to increasing amounts of FMS IB has been demonstrated.
AN INVESTIGATION OF SODIUM AND CALCIUM COMPETITION IN VASCULAR SMOOTH MUSCLE
Authors: Nash Charles W. , Luchka Elizabeth V. , Jhamandas K. H.
Published: April 2011

Isolated loops of rabbit aorta tissue in modified Krebs bicarbonate solutions were stimulated and contractile responses were recorded. The [Na+] was lowered by bathing the tissues in a sucrose-substituted Krebs solution containing half the normal sodium content. Responses of the vascular tissue to noradrenaline (NA) and to electrical stimulation were plotted against the values for the activity ratio of [Ca++]:[Na+]2 which was varied by changing the calcium and the sodium content of the solution. When an 18 minute equilibration period was allowed after reducing the sodium content no clear potentiation of response was observed, but when only 1 minute was allowed for equilibration to the reduced sodium concentration a definite potentiation was observed regardless of the level of external calcium. When the responses to fixed stimulations were plotted as indicated above, they did not fall along a common regression line but formed two distinctly separate regression lines dependent upon the [Na+]. It was therefore concluded that no simple Na and Ca competition for a specific anionic site functions to control the response of this vascular tissue. It was further concluded that the potentiating effects of a reduced external sodium can be explained on the basis of changes in the ratio of Nain:Naout such that an increase in the ratio increases the effectiveness of the stimulation, perhaps by rendering the membrane temporarily less stable.
STUDIES ON HABITUATION TO COLD PAIN
Authors: LeBlanc Jacques , Potvin Pierre
Published: April 2011

It was possible to produce habituation to cold in a group of human subjects by immersing the left hand in cold water for [Formula: see text] minutes twice a day for 19 days. The right hand did not adapt. Another group of subjects was exposed similarly with the difference that an anxiety test (mental arithmetic test) was always given simultaneously with the cold-water test. In this second group the original blood pressure response, i.e. for the first day, was greater than in the first group because of the cumulative effects of the two tests. After 19 days definite evidence was obtained for adaptation to these two tests administered together. However, when these tests were given separately to the second group, no adaptation was evident; adaptation occurred only to both tests given simultaneously. These results indicate that no adaptation develops to cold per se if the subjects are distracted from cold discomfort. It was also found that adaptation of one hand to cold water not only failed to induce adaptation in the opposite hand but even reinforced responses of the unadapted hand. These findings suggest a participation of the central nervous system in adaptation to cold pain, and tend to minimize the importance of local peripheral changes.
MORPHOLOGIC EFFECTS OF VASOACTIVE DRUGS
Authors: Jasmin Gaëtan
Published: April 2011

Studies on anoxic tissue changes that result from the administration of vasoactive drugs given at a maximally tolerable dose to rats indicate that the changes in hemodynamics constitute a determining factor in the development of lesions at diverse organ levels. There was a difference in the nature and the location of the ischemic changes, which was shown after the prolonged administration of these drugs in increasing dosage or after the simultaneous administration of them for a relatively short period. It seems that impairment of veinous drainage largely accounts for the adverse cardiovascular effect of sympathomimetic amines. This assumption is supported by the fact that it is possible to reproduce essentially similar pathologic changes by surgical occlusion of the efferent vessels.
HISTAMINE, MAGNESIUM DEFICIENCY, AND THYMIC TUMORS IN RATS
Authors: Bois P. , Beaulnes A.
Published: April 2011

Histamine was measured in the plasma, liver, and thymus of male rats fed a magnesium-deficient diet for 65 days. Histological study of the thymus was also performed. Histamine levels in plasma and tissue increased rapidly and reached a maximum after 10 days of deficiency. Later on, the level of histamine in deficient animals decreased and fluctuated but was usually higher than in the controls. One rat killed after 60 days of deficiency showed a very large thymus, weighing 1.8 g, which extended into the thoracic cavity. Histological study revealed a complete replacement of the normal thymic cells by large basophilic lymphocytes invading the neighboring organs including the heart muscle. The tumor was transplanted successfully in normal rats receiving a well-balanced diet. Another smaller tumor was found in an animal killed at 65 days. Thymuses of control animals were all normal. The development of tumors of the thymus in magnesium-deficient rats is discussed in connection with the changes in tissue histamine.
ON THE EFFECT OF THE THYROID ON THE METABOLISM OF FREE FATTY ACIDS AND CHOLESTEROL IN FASTING RATS
Authors: Felt V.
Published: April 2011

Fasting markedly influences the effect of l-thyroxine on the metabolism of free fatty acids (FFA) and cholesterol in rats. In fed rats thyroxine raises the FFA content of serum and of adipose tissue and increases the liberation of FFA from the latter; in some animals there also occurs an increase in serum cholesterol. These differences are absent in fasting animals. After 48 hours of fasting, serum FFA and FFA liberation from adipose tissue are higher in controls than in thyroxine-treated animals. Total body oxygen consumption remains increased in thyroxine-treated animals even after 48 hours of fasting. Data are given on changes in glycemia, serum uric acid, and heart weight. Phentolamine in vitro was without effect on the liberation of FFA from adipose tissue either in thyroxine-treated animals or in controls.
VITAMIN A TRANSPORT IN THE RAT
Authors: Veen M. J. , Beaton G. H.
Published: April 2011

Rats deficient in vitamin A and maintained on diets containing 0, 4, or 20% protein (casein) were repleted orally with 0, 10, 40, 80, or 160 μg vitamin A alcohol per day for 7 days. Plasma vitamin A rose with increasing amounts of administered vitamin A until a plateau was reached (at the dose level of 10 μg in the 0% protein group, and the dose level of 40 μg in the other groups), suggesting that plasma saturation with vitamin A had occurred. This was supported by an increase in the deposition of the vitamin in the liver at the dose level of 40 μg vitamin A. The actual level of plasma vitamin A attained at plasma saturation varied directly with the amount of dietary protein fed and, consequently, with plasma protein concentration, but was limited by food restriction in a control group fed a diet containing 20% protein to a level well below that obtained by a control group fed ad libitum with the same diet.Plasma vitamin A was shown to be statistically related to plasma albumin at all levels of administration of the vitamin, and to α1-globulin after plasma saturation with vitamin A had occurred.The data indicate the existence of a plasma protein carrier for vitamin A. The participation of an albumin subfraction in the transport mechanism is discussed.
SERUM BINDING AND BILIARY CLEARANCE OF TRIIODOTHYRONINE IN COLD-ACCLIMATED RATS
Authors: Cottle W. H. , Veress A. T.
Published: April 2011

The more rapid biliary clearance of thyroid hormones resulting from cold acclimation in rats may be the result of an increased capacity of the liver to remove hormone from the blood and (or) to a decreased affinity of the hormone for thyroid-binding protein. The binding of labelled L-triiodothyronine to serum proteins of cold- and warm-acclimated rats has been compared in vitro. Less label was found to bind to protein in sera from cold-acclimated rats, which suggests that a decrease in affinity of thyroid hormones for the binding protein may contribute to the increased biliary clearance found.
EFFECTS OF EXERCISE AND A CHOLESTEROL-FREE DIET ON HUMAN SERUM LIPIDS
Authors: Goode R. C. , Firstbrook J. B. , Shephard R. J.
Published: April 2011

Six male subjects were maintained on a diet free of all animal fats for 54 days; carbohydrate intake was increased to maintain an approximate caloric balance. Serum cholesterol decreased progressively to a low plateau over the first 3 weeks, and thereafter showed a small rise, suggesting increased synthesis. Treadmill exercise sufficient to increase daily energy expenditure by a sixth was carried out for 14 days during the phase of increased synthesis. Serum cholesterol levels did not differ significantly between exercised and control subjects, but serum triglycerides decreased significantly (P < 0.05) over the exercise period.
SECRETION OF TESTOSTERONE BY THE EUTOPIC AND THE CRYPTORCHID TESTES IN THE SAME DOG
Authors: Eik-Nes Kristen B.
Published: April 2011

The concentration of testosterone has been measured in spermatic venous blood from eutopic and cryptorchid testes in the same anesthetized dog in experiments lasting for 90 minutes. Both testes secreted testosterone and increased production of the hormone following intravenous administration of gonadotrophin. The production of testosterone by the cryptorchid testis was, however, lower than that by the eutopic organ thus demonstrating that the condition of cryptorchism is associated with decreased secretion rates of testosterone in the canine.
THE CLEARING FACTOR LIPASE (CFL) RESPONSE TO SYNTHETIC SULFONATED POLYSACCHARIDES IN THE RAT
Authors: Monkhouse F. C. , Abbott E. C.
Published: April 2011

The clearing factor lipase (CFL) response in rats to the intramuscular and intravenous injection of two synthetic sulfonated polysaccharides (RO1-8307, N-formyl chitosan polysulfuric acid, from Hoffmann – La Roche; and Heparinoid G-31150, a breakdown product of polygalacturonic acid, from Geigy (Canada) Ltd.) has been studied in comparison with that of heparin. The intravenous studies showed that both synthetic drugs released adequate levels of CFL but, on a weight basis, were less effective than heparin. Daily intramuscular doses of 20 mg of RO1-8307, with its very low anticoagulant activity, were well tolerated by rats for periods of 5 to 6 weeks. With this dose continuous release of CFL was maintained. After 2 weeks of continuous treatment, there was a measurable decrease in the peak plasma level of CFL following injection but the duration of response was not decreased.