bluuebunny/crossref_metadata_2025 huggingface dataset:
Sarpogrelate diminishes changes in energy stores and ultrastructure of the ischemic-reperfused rat heart
Authors: Temsah Rana M , Kumamoto Hideo , Takeda Nobuakira , Dhalla Naranjan S
Published: April 2011

Although the involvement of serotonin in exacerbating vascular abnormalities in ischemic heart disease has been established, its role in mediating changes in cardiac function due to ischemia reperfusion (IR) is poorly understood. The aim of this study was to investigate the effect of a serotonin blocker, sarpogrelate (5-HT2Aantagonist), in preventing cardiac injury due to IR. Isolated rat hearts were subjected to 30 min of global ischemia followed by 1 h of reperfusion. Sarpogrelate (50 nM-0.9 µM) was infused 10 min before ischemia as well as during the reperfusion period. The IR-induced changes in left ventricular developed pressure, left ventricular end diastolic pressure, rate of pressure development, and rate of pressure decay were attenuated (P < 0.05) with sarpogrelate treatment. Sarpogrelate also decreased the ultrastructural damage and improved the high energy phosphate level in the IR hearts (P < 0.05). This study provides evidence for the attenuation of IR-induced cardiac injury by 5-HT2Areceptor blockade and supports the view that serotonin may contribute to the deleterious effects of IR in the heart.Key words: ischemia reperfusion, sarpogrelate, serotonin receptor blockade.
Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations
Authors: Gaedigk Andrea , Casley William L , Tyndale Rachel F , Sellers Edward M , Jurima-Romet Malle , Leeder J Steven
Published: April 2011

CYP2C9 is the major P450 2C enzyme in human liver and contributes to the metabolism of a number of clinically important substrate drugs. This polymorphically expressed enzyme has been studied in Caucasian, Asian, and to some extent in African American populations, but little is known about the genetic variation in Native American populations. We therefore determined the 2C9*2 (Arg144Cys) and 2C9*3 (Ile359Leu) allele frequencies in 153 Native Canadian Indian (CNI) and 151 Inuit subjects by PCR-RFLP techniques. We also present genotyping data for two reference populations, 325 Caucasian (white North American) and 102 Chinese subjects. Genotyping analysis did not reveal any 2C9*4 alleles in the CNI, Inuit, Caucasian, or Chinese individuals. The 2C9*2 allele appears to be absent in Chinese and Inuit populations, but was present in CNI and Caucasian subjects at frequencies of 0.03 and 0.080.15, respectively. The 2C9*3 allele was not detected in the Inuit group, but occured in the CNI group (f = 0.06) at a frequency comparable to that of other ethnic groups. This group of Inuit individuals are the first population in which no 2C9*2 or *3 alleles have been detected so far. Therefore, these alleles may be extremely rare or absent, and unless other novel polymorphisms exist in this Inuit group one would not anticipate any CYP2C9 poor metabolizer subjects among this population.Key words: CYP2C9, polymorphism, genotyping, ethnic diversity.
Two steroidal saponins from Camassia cusickii induce L1210 cell death through the apoptotic mechanism
Authors: Candra Ellyawati , Matsunaga Kimihiro , Fujiwara Hironori , Mimaki Yoshihiro , Sashida Yutaka , Yamakuni Tohru , Ohizumi Yasushi
Published: April 2011

Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5α-spirostan-3β-yl 4-O-[2-O-[3-O- (α-L-rhamnopyranosyl)-β-D-glucopyranosyl]-3-O-[4-O-(α-L-rhamnopyranosyl)-β-D-glucopyranosyl]-β-D-glucopyranosyl]- β-D-galactopyranoside) and tigogenin hexasaccharide-2 (TGHS-2, (25R)-5α-spirostan-3β-yl 4-O-[2-O-[3-O- (β-D-glucopyranosyl)-β-D-glucopyranosyl]-3-O-[4-O-(α-L-rhamnopyranosyl)-β-D-glucopyranosyl]-β-D-glucopyranosyl]- β-D-galactopyranoside), were isolated from the fresh bulbs of Camassia cusickii. In murine leukemic L1210 cells, both compounds showed cytotoxicity with an EC50 value of 0.06 µM. The morphological observation revealed that TGHS-1 and TGHS-2 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. The cell death was confirmed to be apoptosis by Annexin V binding to phosphatidylserine in the cell membrane and excluding propidium iodide. A typical apoptotic DNA ladder and the cleavage of caspase-3 were observed after treatment with TGHS-1 and TGHS-2. In the presence of both the compounds, cells with sub-G1 DNA content were detected by flow cytometric analysis, indicating that TGHS-1 and TGHS-2 (each EC50 value of 0.1 µM) are the most powerful apoptotic saponins known. These results suggest that TGHS-1 and TGHS-2 induce apoptotic cell death through caspase-3 activation.Key words: steroidal saponin, tigogenin hexasaccharide, apoptosis, DNA fragmentation, murine leukemic L1210 cells.
Summary of Final Report: Space life sciences planning workshop (SLSPW) June 5-7, 2000 Mont Tremblant, Québec
Authors: Ledsome John R
Published: April 2011

A Space Life Sciences Planning Workshop was sponsored by the Canadian Space Agency to identify key questions in the major research areas supported by the Life Sciences Program, to identify Canadian strengths and capabilities as they relate to these research areas, and to make recommendations for the future directions of the Life Sciences Program. The conclusions reached by the workshop participants have been presented to the Canadian Space Agency. This report is a summary of those conclusions.Key words: microgravity, Canadian Space Agency, bone loss, muscle loss, cardiovascular, radiation, neuroscience.
Influence of IL-6 on MDR and MRP-mediated multidrug resistance in human hepatoma cells
Authors: Lee Gigi , Piquette-Miller Micheline
Published: April 2011

The objective of this study was to examine effects of interleukin-6 (IL-6) on the expression and activity of the drug resistance transporters (MDR1 and MRP) in human hepatoma cell lines. Expression and activity of MDR1 and MRP transporters were examined in IL-6-treated and control HuH 7 and HepG2 cells using semi-quantitative RT-PCR analysis and by rhodamine 123 and 5-carboxyfluorescin efflux assays. Results from RT-PCR demonstrated expression of MRP3, MRP6, and MDR1 in HuH 7 cells and expression of MRP1, MRP2, MRP3, MRP6, and MDR1 in HepG2 cells. Compared with controls, treatment of HuH 7 cells with IL-6 (10 ng/mL, 24 h) resulted in a 1.8-fold increase in MRP-mediated efflux of 5-CF with a corresponding 1.5-fold induction of MRP3 mRNA levels (p < 0.05). Similarly, in HepG2 cells, a 2-fold increase in MRP functional activity and a 1.8-fold induction of MRP1 mRNA levels were seen in the IL-6 treated cells (p < 0.05). Treatment of cells with IL-6 was also found to cause significant reductions in the expression and activity of MDR1 in HuH 7 cells, but not in HepG2 cells. Our data suggest that IL-6 induces MRP expression and activity in human hepatoma cell lines. Suppressive effects of IL-6 on MDR1 expression and activity were also observed in HuH 7 cells. This underscores the importance of examining the regulation of multiple drug resistance proteins as these proteins may have opposing regulatory mechanisms in malignant cells.Key words: P-Glycoprotein, multidrug resistance proteins, hepatocarcinogenesis, cytokines, inflammation.
Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle
Authors: Hawke Thomas J , Lessard Sarah , Vickery Lisa , Lipskie Shonda L , Lindinger Michael I
Published: April 2011

The present study compared ouabain-sensitive unidirectional K+flux into (JinK) and out of (JoutK) perfused rat hindlimb skeletal muscle in situ and mouse flexor digitorum brevis (FDB) in vitro. In situ, 5 mM ouabain inhibited 54 ± 4% of the total JinK in 28 ± 1 min, and increased the net and unidirectional efflux of K+within 4 min. In contrast, 1.8 mM ouabain inhibited 40 ± 8% of the total JinK in 38 ± 2 min, but did not significantly affect JoutK. In vitro, 1.8 and 0.2 mM ouabain decreased JinK to a greater extent (83 ± 5%) than in situ, but did not significantly affect42K loss rate compared with controls. The increase in unidirectional K+efflux (JoutK) with 5 mM ouabain in situ was attributed to increased K+efflux through cation channels, since addition of barium (1 mM) to ouabain-perfused muscles returned JoutK to baseline values within 12 min. Perfusion with 5 mM ouabain plus 2 mM tetracaine for 30 min decreased JinK 46 ± 9% (0.30 ± 0.03 to 0.16 ± 0.02 µmol·min1·g1), however tetracaine was unable to abolish the ouabain-induced increase in unidirectional K+efflux. In both rat hindlimb and mouse FDB, tetracaine had no effect on JoutK. Perfusion of hindlimb muscle with 0.1 mM tetrodotoxin (TTX, a Na+channel blocker) decreased JinK by 15 ± 1%, but had no effect on JoutK; subsequent addition of ouabain (5 mM) decreased JinK a further 32 ± 2%. The ouabain-induced increase in unidirectional K+efflux did not occur when TTX was perfused prior to and during perfusion with 5 mM ouabain. We conclude that 5 mM ouabain increases the unidirectional efflux of K+from skeletal muscle through a barium and TTX-sensitive pathway, suggestive of voltage sensitive Na+channels, in addition to inhibiting Na+/K+-ATPase activity.Key words: cardiac glycoside, Na,K pump, K+channels, Na+channels, perfused rat hindlimb, flexor digitorum brevis, TTX, barium, tetracaine.
Actions of putative chloride channel blocking agents on canine lower esophageal sphincter (LES)
Authors: Jury Jennifer , Patel Mehul , Bowes Tim , Daniel E E
Published: April 2011

Niflumic acid (NA), a putative Cl-channel blocker, has provided pharmacological evidence that Cl-channel closures mediate hyperpolarization caused by NO in gastrointestinal smooth muscle. However, NA caused concentration- dependent relaxation of canine lower esophageal sphincter (LES) and failed to inhibit NO-mediated relaxations. DIDS also did not inhibit NO-mediated relaxations, but did abolish them when present with 20 mM TEA (tetraethyl ammonium ion), which was also ineffective alone. TEA reversed NA-induced relaxations, but with NA it did not inhibit NO-mediated relaxations. We investigated the modes of action of these agents further. Neither nerve-function block nor block of NOS activity affected the inhibition of LES tone by NA. In patch-clamp studies, NA increased outward currents from 30 to + 90 mV when [Ca2+]pipette was 50 nM. This was prevented by 20 mM TEA, but not by prior inhibition of NOS. At 200 nM [Ca2+]pipette, TEA markedly reduced outward currents, but did not prevent the increase from subsequent NA. In contrast, under similar conditions, application of DIDS after 20 mM TEA further reduced outward currents. When the patch pipette contained CsCl and TEA to block K+ currents, NA had no significant effect on currents between 50 and +90 mV. Thus, NA acted by opening K+ channels: some TEA-sensitive and some not. It had no detectable effect on currents when K+ channels were blocked. We conclude that NA is an unreliable pharmacological tool to evaluate Cl-channel contributions to smooth muscle function. DIDS did not open K+ channels. Decreases in outward currents from DIDS may result from inhibition of K+ currents or currents carried by Cl at depolarized membrane potentials.Key words: DIDS, niflumic acid, NO actions, smooth muscle.
The vaso-contractile action of zooxanthellatoxin-B from a marine dinoflagellate is mediated via Ca2+influx in the rabbit aorta
Authors: Moriya Takahiro , Furukawa Ken-Ichi , Nakamura Hideshi , Murai Akio , Ohizumi Yasushi
Published: April 2011

We previously showed that zooxanthellatoxin-B, isolated from dinoflagellate, caused a sustained contraction of the aorta in an external Ca2+-dependent manner. To clarify the role of Ca2+in this action, we examined the effects of zooxanthellatoxin-B as well as a depolarizing stimulus (60 mM KCl), using the simultaneous recording for cytosolic Ca2+level (fura-2) and developed tension in the rabbit aorta. KCl (60 mM) elicited a rapid cytosolic Ca2+elevation followed by a pronounced contraction, and time required for half-maximum contraction was 2 min. Zooxanthellatoxin-B caused an increase in cytosolic Ca2+followed by a gradual contraction, with a time for half-maximum contraction of 510 min in a concentration-dependent manner. We found a strong correlation between Ca2+elevation and the contraction in zooxanthellatoxin-B action. In a Ca2+-free solution, zooxanthellatoxin-B caused neither the contraction nor the increase in cytosolic Ca2+. Furthermore, both pre- and post-treatment with verapamil, a voltage-operated Ca2+-channel blocker, partially suppressed both an increase in cytosolic Ca2+and the contraction by zooxanthellatoxin-B. Zooxanthellatoxin-B-induced contraction was also inhibited by other voltage-operated Ca2+-channel blockers: nifedipine or diltiazem. These results suggest that zooxanthellatoxin-B-elicited contraction is caused by a Ca2+influx into the smooth muscle cells, partially via voltage-operated Ca2+channels.Key words: zooxanthellatoxin, Ca2+imaging, rabbit aorta, contraction, voltage-operated Ca2+-channels.
Time course in calpain activity and autolysis in slow and fast skeletal muscle during clenbuterol treatment
Authors: Douillard Aymeric , Galbes Olivier , Rossano Bernadette , Vernus Barbara , Bonnieu Anne , Candau Robin , Py Guillaume
Published: April 2011

Calpains are Ca2+cysteine proteases that have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. Cumulative evidence also suggests that β2-agonists can lead to skeletal muscle hypertrophy through a mechanism probably related to calcium-dependent proteolytic enzyme. The aim of our study was to monitor calpain activity as a function of clenbuterol treatment in both slow and fast phenotype rat muscles. For this purpose, for 21 days we followed the time course of the calpain activity and of the ubiquitous calpain 1 and 2 autolysis, as well as muscle remodeling in the extensor digitorum longus (EDL) and soleus muscles of male Wistar rats treated daily with clenbuterol (4 mg·kg–1). A slow to fast fiber shift was observed in both the EDL and soleus muscles after 9 days of treatment, while hypertrophy was observed only in EDL after 9 days of treatment. Soleus muscle but not EDL muscle underwent an early apoptonecrosis phase characterized by hematoxylin and eosin staining. Total calpain activity was increased in both the EDL and soleus muscles of rats treated with clenbuterol. Moreover, calpain 1 autolysis increased significantly after 14 days in the EDL, but not in the soleus. Calpain 2 autolysis increased significantly in both muscles 6 hours after the first clenbuterol injection, indicating that clenbuterol-induced calpain 2 autolysis occurred earlier than calpain 1 autolysis. Together, these data suggest a preferential involvement of calpain 2 autolysis compared with calpain 1 autolysis in the mechanisms underlying the clenbuterol-induced skeletal muscle remodeling.
RELEASE OF THYROTROPHIN IN VIVO AND IN VITRO BY SYNTHETIC NEUROHYPOPHYSIAL HORMONES
Authors: LaBella Frank S.
Published: April 2011

The influence of synthetic oxytocin and synthetic lysine-8-vasopressin on the release of thyrotrophin (TSH) from slices of the "basophilic" zone of bovine anterior pituitary glands was determined. Up to 10-fold stimulation of TSH release occurred in the presence of the peptide hormones at low concentrations (approximately 10−11to 10−9 M). Concentrations greater than 10−9 M were less stimulatory, ineffective, or inhibitory. In general, vasopressin stimulated at lower concentrations than did oxytocin. The dose–response curve of oxytocin began to descend at lower concentrations than did that of vasopressin.Stimulation of I131discharge from the thyroids of propylthiouracil (PTU)-treated, day-old chicks was produced by the intraperitoneal injection of as little as 4 ng vasopressin or 25 ng oxytocin. As the injected dose of either peptide was increased beyond an optimal level, there was less enhancement of I131discharge, and, with further increases, inhibition. The decreasing response began with lower doses of oxytocin than of vasopressin. The similarities of the dose–response curves of thyroid I131discharge and of in vitro release of TSH indicate that the in vivo effects of injected neurohypophysial peptides are mediated through the release of endogenous TSH.
DISTRIBUTION IN THE RAT OF PARTIALLY DENATURED IODINATED SERUM ALBUMIN
Authors: Manske Robert F. , Blau Monte
Published: April 2011

The distribution of heated radioiodinated human serum albumin (IHSA) was investigated in the rat.Increase in duration of heat treatment at 70 °C resulted in increased liver uptake. The fraction of the injected dose remaining in the blood decreased with increase in duration of heat treatment.Similarly, increase in temperature of heating from 65 °C to 75 °C resulted in increased liver uptake. The fraction of the injected dose remaining in the blood decreased with increase in temperature of heating.The liver:blood radioactivity concentration ratios provide an index of the degree of heat denaturation of iodinated human serum albumin preparations.
ISOLATION AND PROPERTIES OF ANTICOAGULANTS FROM FIBRINOLYSED AND HUMAN HEART-PUMP PLASMAS
Authors: Triantaphyllopoulos D. C. , Triantaphyllopoulos E.
Published: April 2011

A method is described for the isolation from plasma of breakdown products of fibrinogen having anticoagulant properties. Intact fibrinogen is removed by addition of ether (to 11% by volume) and the anticoagulant is then precipitated by 25% ammonium sulphate saturation of the supernatant. With this method, anticoagulant fractions from in vitro lysed human plasma, human heart-pump plasma, and in vivo lysed rabbit plasma have been isolated. The electrophoretic patterns of the fractions isolated from lysed human plasma and heart-pump plasma were similar to that of AFIF and consisted of two main components, one exhibiting the same mobility as intact fibrinogen and another being more electronegative. Both fractions were found to possess antithrombin activity. The fraction isolated from plasma of rabbits injected with fibrinolysin was separated into three main components. The antithrombin activity of lysed plasmas, human and rabbit, increased with increasing pH values, while that of the heart-pump plasma, after an initial increase, seemed to decrease above pH 7.8. In further similarity to AFIF, all fractions counteracted the procoagulant effect of protamine sulphate, but only the fraction isolated from adsorbed lysed plasma showed an antithromboplastic effect as well. Measurement of optical densities at 600 mμ of mixtures of fibrinogen and the anticoagulants, after addition of thrombin, indicated that all anticoagulants: (a) delayed the beginning of polymerization; and (b) decreased the opacity of the resulting clot.No correlation could be established between the variable levels of antithrombin activity of the fraction isolated from the heart-pump plasma and the severity of the condition of the patient.
A STUDY OF THE LEVELS OF EXTRACTABLE INSULIN OF GUINEA PIG PANCREAS
Authors: Davidson J. K. , Haist R. E.
Published: April 2011

The guinea pig was reported to have a very low insulin concentration in the pancreas. It was found that this was true for male (246–378 g) and female (236–318 g) immature guinea pigs but that mature male (760–1023 g) and female (476–554 g) guinea pigs have considerably higher levels (e.g. 1.4 units per gram pancreas for mature males as compared to 0.26 unit/g for immature males).
EFFECT OF CYPROHEPTADINE ON A TOPICAL CALCIFICATION IN THE RAT
Authors: Dieudonné Jean M.
Published: April 2011

In the rat, cyproheptadine prevents the soft-tissue calcification elicited by various mast-cell depletors (e.g. 48/80, polymyxin) at their subcutaneous injection site whereas it aggravates that induced by hexadimethrine, another mast-cell depletor. This action does not appear to result from the antihistaminic–antiserotonin properties of cyproheptadine which showed, in addition, an in vitro antiheparin effect.
IN VIVO ESTIMATION OF ELASTIC CHARACTERISTICS OF THE ARTERIES IN THE LOWER EXTREMITIES OF MAN
Authors: Carter Stefan A.
Published: April 2011

Arterial distensibility can be studied in intact man by measuring the pulse wave velocity. Since distensibility is known to vary with pressure, in the present study pulse wave velocity was measured over a range of transmural pressures. This was achieved by applying positive or negative pressures to the outside of the extremity while the velocity was measured between the groin and the foot, using intra-arterial needles. Twenty-seven subjects were studied. Distensibility, when plotted against transmural diastolic pressure on logarithmic coordinates, declined linearly with increasing pressure up to at least 70 mm Hg. Above 100 mm Hg there was less change or no further consistent change in distensibility. The slopes, which represent logarithmic relationship between distensibility and pressure in the pressure range up to 70 mm Hg, have been used as an index of the elastic characteristics of the arteries. Body heating or cooling, intravenous norepinephrine or Arfonad had little or no effect on these slopes, which suggests that they are relatively independent of the physiologic state of the subject. The finding that the slopes decreased with increasing age indicates that this method may prove useful in the study of normal and abnormal states of the arteries.
FACTORS IN THE REDUCED SURVIVAL TIME DURING STARVATION IN THE COLD OF RATS PREVIOUSLY FED A LOW-PROTEIN DIET
Authors: Beaton J. R. , Feleki V. , Stevenson J. A. F.
Published: April 2011

Male Wistar rats fed a low-protein diet (5% by weight) did not withstand subsequent deprivation of food at 5 °C or 23 °C as long as controls that had been fed a 20% protein diet isocalorically. This was also true in Sprague–Dawley rats which were studied only at 5 °C. This effect of the low-protein diet was not attributable to differences in food consumption, or in "resting" oxygen consumption. The rats fed low-protein had somewhat less fat when deprived of food but, perhaps more importantly, appeared to use less of their reserves of energy during food deprivation. Apparent water loss and thus dehydration appeared to be greater in these animals.
POTENTIATION BY THIOPENTAL OF CYCLOPROPANE–ADRENALINE CARDIAC ARRHYTHMIAS
Authors: MacCannell Keith L. , Dresel Peter E.
Published: April 2011

Thiopental has been used for induction of anaesthesia in most, experimental and clinical investigations of cyclopropane–adrenaline cardiac arrhythmias. We have compared the effects of adrenaline under cyclopropane (cyclo) anaesthesia in dogs with those observed under thiopental (thio) anaesthesia and thiopental–cyclopropane (thio–cyclo) anaesthesia. Bigeminal rhythm occurring in response to small doses of adrenaline is observed in less than half the animals under cyclo or thio anaesthesia, but is observed in over 90% when the two anaesthetic agents are present. The dose of adrenaline necessary to produce multifocal or ventricular fibrillatory rhythms also appears to be greater under cyclo than under thio–cyclo, but exact quantification is difficult because of the rapid development of tachyphylaxis to larger doses of adrenaline. The duration of the effect of thiopental outlasts by many hours its usual anaesthetic action. Intravenous injections of "subeffective" doses of adrenaline produce bigeminal rhythm if they are preceded by injection of small doses of thiopental into the left circumflex coronary artery. This rarely occurs if thiopental is injected into the left anterior descending coronary artery. Previous evidence has suggested that the bigeminal beat arises in the atrioventricular node or upper bundle of His and that the left circumflex coronary artery supplies this area. It is thus probable that thiopental exerts its action in the upper part of the conduction system. It is concluded that induction of anaesthesia with thiopental plays a considerable role in the "cyclopropane–adrenaline" cardiac arrhythmias described in the literature.
MOLECULAR STRUCTURE–ACTIVITY RELATIONSHIPS OF COMPOUNDS PROTECTING RATS AGAINST OXYGEN POISONING
Authors: Wood J. D. , Watson W. J.
Published: April 2011

A number of compounds have been studied to correlate their molecular structure with their efficacy in protecting male Wistar rats against the toxic effects of exposure to oxygen at 75 p.s.i. gauge pressure for 45 minutes. Compounds with a straight chain, 2C to 4C in length, containing one amino and one carboxyl group located at opposite ends of the chain were the most potent protective agents. The presence of an additional amino or carboxyl group or an alkyl side chain in the molecule greatly reduced the protective action as did the removal of either the amino or carboxyl group from the active molecule. The length of the carbon chain within the range 2C to 4C was not critical with respect to the activity of the compound but the position of the amino group appeared to have some bearing on activity, the degree of protection being at a maximum when the amino group was attached to the terminal carbon atom furthest from the carboxyl group. The similarity between the protective action of the amino acids and their depressant action on neurones is commented upon and possible mechanisms involved in oxygen poisoning and protection therefrom by amino acids are discussed.
BIOLOGICAL EFFECTS OF ANOREXIGENIC AND FAT-MOBILIZING SUBSTANCES FROM RAT URINE
Authors: Beaton J. R. , Szlavko A. J. , Box B. M. , Stevenson J. A. F.
Published: April 2011

An anorexigenic and fat-mobilizing substance (FMS I) previously extracted from the urine of fasting rats has been further fractionated, on the basis of solubility, in alkaline or neutral solutions respectively into FMS IA and FMS IB. When a single subcutaneous injection was administered to rats, FMS I and IA, but not IB, caused a decrease of food intake and of body weight; FMS I and IB, but not IA, caused an increase in serum free fatty acids and in liver fat. In addition, IB caused a significant increase in blood ketones. All three fractions caused hypoglycemia. From these observations, it is concluded that the anorexigenic property is associated with fraction IA and the fat-mobilizing properly is assocatied with fraction IB. FMS I is not excreted by rats during feeding at an environmental temperature of 24 °C but is excreted by fed rats during acute exposure to cold (5 °C), a situation in which fat mobilization is known to occur. Urine extracts from fasting, hypophysectomized rats contained no fat-mobilizing activity in vitro or in vivo.
MEAL-EATING AND LIPOGENESIS IN VITRO OF RATS FED A LOW-PROTEIN DIET
Authors: Beaton J. R. , Feleki V. , Szlavko A. J. , Stevenson J. A. F.
Published: April 2011

The response of male rats to the restriction of food intake to 2 hours each day for 14 to 16 days has been assessed by the measurement of food intakes, body weights, liver glycogen concentrations, and lipogenesis of adipose tissue (C14-acetate incorporation in vitro). The animals were fed either a 20% casein diet (controls) or an isocaloric 5% casein diet. As a consequence of meal-eating, and regardless of dietary protein level, the average daily food intake and body weight gain were decreased whereas the lipogenesis in vitro and liver glycogen concentration were increased in comparison with rats fed ad libitum,which is in agreement with earlier findings using normal diets. These observations suggest that the decreased body fat of rats fed a 5% casein diet is not a consequence of an impaired ability of adipose tissue to synthesize fat.
ACUTE TOXICITY STUDIES ON ETHANOL, PROPANOL, AND BUTANOL
Authors: MacGregor D. C. , Schönbaum E. , Bigelow W. G.
Published: April 2011

Three series of 10 dogs each were used to study the effects of intravenously administered ethanol, propanol-1, and butanol-1. In normothermic dogs, with supported respiration and nitrous oxide anaesthesia (after induction), the mean lethal doses for ethanol, propanol-1, and butanol-1 were 4.90, 2.42, and 1.26 g/kg respectively. At a constant infusion rate, the blood alcohol levels increased almost linearly with time. Relationships between ethanol, propanol-1, and butanol-1 blood levels and blood pressure, pulse, and electrocardiogram were established. Two minutes cardiac standstill occurred at the following blood levels: ethanol, 1499 mg/100 ml; propanol-1, 713 mg/100 ml; butanol-1, 279 mg/100 ml.
AN ATTEMPTED REVERSAL OF THALIDOMIDE EMBRYOPATHY IN THE RAT BY GLUTAMINE
Authors: McColl J. D. , Globus M. , Robinson S.
Published: April 2011

Skeletal, cardiovascular, and urethral defects were observed in the 21-day-old offspring of Sprague–Dawley rats following administration of thalidomide (2% of diet) during the entire gestation period. The fetuses of animals which received either l-glutamic acid or l-glutamine (2% of diet each), in addition to thalidomide, showed essentially the same incidence and type of gross defects as those from the thalidomide-treated mothers.The ineffectiveness of these essential growth factors to reduce the embryopathy significantly is interpreted to indicate that they are not predominately involved in the teratogenic action of thalidomide in the rat.
EPILEPTOGENIC FOCI IN RABBIT BRAIN
Authors: Leclercq Bruno , Segal Mark
Published: April 2011

Regions highly sensitive to generating the afterdischarge response exist in the cortex, rhinencephalon, and nucleus medialis thalami. The cortical foci lie in the deeper regions of the cortex along the border of separation between gray and white matter. Precise electrode placement precludes threshold variability. The experimental evidence in rabbit correlates with similar evidence obtained in the cat and reported for the guinea pig.
THE TAIL OF THE RAT, IN TEMPERATURE REGULATION AND ACCLIMATIZATION
Authors: Rand R. P. , Burton A. C. , Ing T.
Published: April 2011

The role of the tail of the Wistar white rat in its temperature regulation was studied, and a new index of acclimatization was found. Blood flow in the tail was measured by venous-occlusion plethysmography at environmental temperatures from 17 to 33 °C. There is an abrupt vasodilation between 27 and 30° with flow rising from less than 5 ml to about 40 ml/100 ml tissue per minute. Measurement of heat loss by a gradient calorimeter on the tail showed a similar reflex vasodilation at a critical vasodilation temperature (TCVD). After vasodilation the tail can lose up to 20% of the total heat production of the rat. The skin temperature of the tail was used as an index of vasodilation to determine whether the critical temperature shifted with acclimatization to 11 °C, 20 °C, and 30 °C. There is a decrease in TCVD of about 6° after acclimatization to cold (TCVD = 20 °C for 11 °C, 26 °C for 20 °C). After acclimatization to 30 °C, no vasodilation was found at temperatures up to 33 °C. The maximum heat loss of the tail is greatly increased after cold acclimatization. The mechanism of the shift is probably a change in sensitivity of thermal receptors on the tail, due to an increased vascularity (increased thermal conductivity) of the local tissues.
LYMPHATIC ABSORPTION OF CHOLESTEROL IN THE DOG FOLLOWING CORN OIL AND BUTTERFAT FEEDING
Authors: Huang T. C. , Kuksis A.
Published: April 2011

Lymphatic absorption of cholesterol was determined in 11 unanaesthetized dogs with thoracic duct bypasses or fistulae, following the administration of corn oil or butterfat with and without cholesterol supplementation. Comparisons based on fixed amounts of lymph or total lymph lipid, as well as the estimated overall sterol recoveries, showed that the conclusions can vary depending on how the calculations are done. On the basis of data collected in the same animal, it was concluded that the glyceride type of dietary fat had no significant effect on lymphatic absorption of cholesterol in the dog. The feeding of butterfat, corn and coconut oils, or simple triglycerides to different animals resulted in widely varying lymph cholesterol levels, which could not be correlated with any of the variables under direct experimental control.
RELATION OF OXYGEN UPTAKE TO BODY WEIGHT OF RATS AT DIFFERENT ENVIRONMENTAL TEMPERATURES
Authors: Gridgeman N. T. , Heroux O.
Published: April 2011

Statistical analysis of data on the oxygen consumption of rats (Sprague–Dawley strain; records covering several years of experimentation in one laboratory) indicated that the relation between oxygen uptake and body weight is not constant. Kleiber's case for a linear relation between oxygen uptake and the [Formula: see text] power of body weight for homeotherms in general under normal environmental conditions is not impugned by the present findings. Under abnormal experimental conditions, particularly as regards environmental temperature, the use of the analysis of covariance is recommended to best allow for the effect of body weight on oxygen uptake.
EFFECTS OF INTRA-ARTERIAL PERFUSIONS ON ELECTRICAL ACTIVITY AND ELECTROLYTE CONTENTS OF DOG SMALL INTESTINE
Authors: Daniel E. E.
Published: April 2011

The mechanisms underlying the periodic depolarizations (slow waves) in longitudinal muscle of the small intestine were studied in vivo in dogs by means of intra-arterial perfusions of solutions with altered electrolyte concentrations or with added metabolic inhibitors. Perfusion of solutions containing reduced sodium, potassium, or chloride concentrations markedly altered electrolyte concentrations in intestinal muscle but did not necessarily alter intestinal slow waves seriously. However, when lithium ion was substituted for sodium ion serious depression of slow waves occurred. This was also found with ouabain, NaF, and Na2EDTA, substances which, like lithium, are believed to inhibit the active transport process directly. Iodoacetate and dinitrophenol had little depressant effect on intestinal slow waves in amounts sufficient to cause downhill ion movements. NaCN or 1,10-phenanthroline depressed slow waves, but the effect of NaCN was largely prevented by prior reserpinization of the dog. The depressant effects of lithium ion, ouabain, NaF, and Na2EDTA were diminished but not abolished by reserpinization. It was concluded that lower amounts of inhibitors of the active transport process abolished intestinal slow waves by causing the release of catecholamines from intrinsic nerve endings in the intestine. The released catecholamines then depressed slow waves. In higher amounts, inhibitors of the active transport process depressed intestinal slow waves by a direct action, unaffected by reserpinization. Intestinal slow waves were therefore postulated to originate from the oscillatory activity of an electrogenic sodium pump.Perfusates with elevated sodium or potassium concentration initiated action potentials in intestinal longitudinal muscle. These action potentials were blocked by atropine and hexamethonium. In reserpinized animals, Na2EDTA or large amounts of ouabain also initiated action potentials which were stopped or prevented by atropine. It was postulated that all these procedures caused acetylcholine release from intrinsic parasympathetic nerves and that the common mechanism was displacement of mediator by net entrance of sodium ion. This same mechanism may also have accounted for the release of catecholamines from intrinsic sympathetic nerves mentioned above.
BLOOD TRANSAMINASE ACTIVITIES IN VITAMIN B6DEFICIENCY: SPECIFICITY AND SENSITIVITY
Authors: Cheney M. C. , Curry D. M. , Beaton G. H.
Published: April 2011

The lowering of blood glutamic–oxaloacetic (GOT) and glutamic–pyruvic (GPT) transaminase activities was found to be specific for vitamin B6deprivation among several B vitamins tested and in the presence of a simultaneous restriction of eight B vitamins, cortisone administration, or variation of dietary protein level. It was found that changes in blood transaminase activity did not always parallel those seen in liver transaminase activity. In the determination of vitamin B6nutritional status, blood GPT activity appeared to be more sensitive than GOT activity and would seem to be as sensitive an indicator as xanthurenic acid excretion after a tryptophan load.
BLOOD TRANSAMINASE ACTIVITIES IN VITAMIN B6 DEFICIENCY: EFFECT OF CONCURRENT THIAMINE AND RIBOFLAVIN DEFICIENCIES
Authors: Cheney M. C. , Beaton G. H.
Published: April 2011

Factorial design experiments in rats revealed that blood transaminase activity was sensitive to vitamin B6 dosage and was not affected by concurrent variation in riboflavin or thiamine administration.The blood transaminase activity was a better index of vitamin B6 nutritional status than was body weight response or liver transaminase activity. Similarly, erythrocyte transketolase activity was found to reflect thiamine dosage, and plasma riboflavin level to reflect riboflavin dosage, regardless of manipulation of pyridoxine dosage.
THE EFFECT OF GLUCAGON ON BLOOD SUGAR AND INORGANIC PHOSPHORUS LEVELS IN NORMOTHERMIC AND HYPOTHERMIC RATS
Authors: Crawford Anne L. , Henderson Margaret J. , Hawkins Rosemary D. , Haist R. E.
Published: April 2011

Injection of glucagon into normothermic rats led to hyperglycaemia, and a significant fall in blood inorganic phosphorus levels. In hypothermic rats (25 °C) the injection of glucagon did not produce hyperglycaemia but the reduction in blood inorganic phosphorus levels was still obtained. Following the administration of glucagon, an increase in the excretion of inorganic phosphorus in the urine was observed in both normothermic and hypothermic rats. The fall in blood inorganic phosphorus level was considered to be due, in part at least, to the effect of glucagon in increasing the excretion of phosphorus in the urine.
THE EFFECTS OF DIPYRIDAMOLE AND NITROGLYCERIN ON CORONARY BLOOD FLOW, MEAN ARTERIAL PRESSURE, AND HEART RATE IN DOGS
Authors: Elliot E. C. , Secord D. , Heath C.
Published: April 2011

The effects of the coronary dilators dipyridamole and nitroglycerin were studied in 21 dogs, either under conditions of constant pulmonary artery inflow (constant PAI experiments) or under conditions of constant arterial pressure as well (constant PAI and AP experiments). The two drugs had different effects on coronary flow in the constant PAI experiments, although both reduced peripheral arterial pressure. Nitroglycerin caused a brief biphasic response, consisting of a peak increase followed by a fall below control, whereas dipyridamole maintained coronary flow above control levels and for a much longer period.In the constant PAI and AP experiments, the biphasic response after nitroglycerin was not observed, and a significant increase in the peak flow over that noted in the constant PAI experiments occurred. With dipyridamole the peak coronary flow was not significantly changed by holding the arterial pressure constant.The implication from the significantly greater coronary flow response after nitroglycerin in the constant PAI and AP experiments compared with that in the constant PAI experiments is that in the latter experiments reduced coronary resistance secondary to nitroglycerin would seem to have been masked by the rapid fall in peripheral pressure. Dipyridamole caused a progressive increase in coronary flow in the face of a reduction in peripheral pressure.
THRESHOLD STUDIES AND ISOLIMINAL MAPPING OF ELECTRICALLY ELICITED AFTERDISCHARGE IN THE CAT BRAIN
Authors: Segal Mark , Leclercq Bruno
Published: April 2011

Thresholds for the afterdischarge response were determined in areas of the brain known to be implicated in clinical epilepsy. Highly susceptible centers were found in the cortex and the hippocampus, and isoliminal regions were mapped in each area. Gradients of threshold voltage were observed in the regions around all of the susceptible centers. The susceptible centers of the cortex were found to lie at the limit of gray and white matter in the walls of the sulci. A relationship was found to exist between the susceptibility of centers responding and the presence of large nucleated cells. Histological verification of electrode placement ruled out the existence of variability in threshold for the afterdischarge response, within as well as between species.
THE CONCENTRATIONS OF PENICILLINS IN THE CEREBROSPINAL FLUID AND BRAIN OF RABBITS WITH EXPERIMENTAL MENINGITIS
Authors: Ruedy John
Published: April 2011

The selection of an antibiotic to treat purulent meningitis is based upon the minimal inhibitory concentration of the drug for the infecting organism and the concentration of the antibiotic in the blood and cerebrospinal fluid following systemic administration. Few antibiotics reach the cerebrospinal fluid of normal animals in appreciable concentrations. All reach higher levels in the presence of meningitis. Several semisynthetic penicillins possess novel properties suggesting that the drugs should be useful in the treatment of meningitis. The distribution of these drugs in the cerebrospinal fluid in meningitis is not known. Experiments were carried out in which the concentrations of nine semisynthetic penicillins were assayed in the blood, cerebrospinal fluid, and brain of rabbits with purulent meningitis. Appreciable concentrations of all penicillins were found in the cerebrospinal fluid. A correlation was shown between the levels reached in the cerebrospinal fluid and the amount of penicillin bound by plasma protein. Cerebrospinal fluid levels did not accurately reflect brain tissue concentrations.
THE INACTIVATION OF ANTITHROMBIN BY ETHER: EVIDENCE AGAINST THE EXISTENCE OF ANTITHROMBIN IV
Authors: Monkhouse Frank C. , Milojevic Susan
Published: April 2011

Citrated defibrinated dog plasma was washed with ether to remove normal antithrombin. At least three washes with three volumes of ether for each wash were required to remove all antithrombin activity. Heparin-cofactor activity was also removed by this treatment. When the prothrombin of this ether-treated plasma was activated, the thrombin activity remained stable in the mixture for several hours. This is in contrast to activated normal plasma, in which the thrombin activity disappears within a few minutes because of the antithrombin content. By adding purified antithrombin to ether-treated plasma, a normal thrombin generation curve was obtained. It has been concluded that there is only one enzymatic antithrombin in plasma.
SUGARS AND HISTAMINE-INDUCED CAPILLARY LEAKAGE
Authors: Adamkiewicz V. W. , Sacra P. J.
Published: April 2011

Capillary leakage of intravenous Evans blue (2% w/v in saline, 0.3 ml per 100 g of rat, 12 hours fasted) was produced by intradermal injections of 0.01 and 0.02 μmoles of histamine in 0.1 ml solution. The leakage was inhibited by topical D-glucose at a histamine to glucose molar ratio of 1:16. Topical sucrose inhibited at a ratio of 1:2 and D- and L-arabinose at 1:32. Higher or lower ratios of the sugars as well as equimolar urea or sodium chloride exerted no significant inhibition. Systemic administration of D-glucose (2, 4, 8 mmoles in 2 ml per 100 g body weight per os), that resulted in hyperglycemias of more than 120 mg/100 ml, also inhibited the histamine-induced capillary leakage.
SOME NINHYDRIN-POSITIVE SUBSTANCES IN THE PLASMA AND URINE OF THE DOG
Authors: Wright L. A. , Nicholson T. F.
Published: April 2011

The dog has been used for much research into various aspects of metabolic and physiological functions, including many studies in the field of amino acids, yet little has been published concerning the pattern of free amino acids in the dog's plasma and urine, and even less on the peptides and other ninhydrin-positive substances. The separation and identification of a number of these ninhydrin-positive substances were carried out by means of three two-dimensional electrophoretic and (or) chromatographic systems and the application of specific and generalized tests for different amino compounds.The amino acids known to be present in the plasma and urine of humans along with α-aminoadipic acid and homocitrulline were also found in those of dogs except for phosphoethanolamine, δ-aminolevulinic acid, α-aminovaieric acid, sarcosine, and glucosamine. The peptides detected in the urine of the dog were anserine, carnosine, cystathionine, α-aspartylglycine, β-aspartylglycine, β-aspartylhistidine, β-aspartylvaline, α-glutamylleucine, γ-glutamylleucine, glycylaspartic acid, and glycylproline. Of these peptides only anserine, carnosine, and α-aspartylglycine could normally be detected in the plasma.
THE USE OF SMALL SKIN SURFACE AREAS FOR WHOLE BODY SWEATING ASSESSMENT
Authors: Custance Arthur C.
Published: April 2011

It is possible to obtain a continuous record of the sweating rate of an active subject by monitoring changes in total body weight. However, elaborate equipment is required that is capable of accommodating the treadmill (or other exercising device) as well as the subject. The balance must be rugged enough to withstand the movements of the subject, yet sensitive enough to respond to small changes in weight. It would be a great convenience to be able, instead, to monitor small representative areas of the skin surface with confidence that they faithfully reflect whole body reactions.In this research, moisture loss from a representative area of the skin of the dorsum under a capsule covering 14 sq. cm was measured by an apparatus which automatically altered the flow of dry air to keep the humidity of the effluent constant. In four subjects exercising on a treadmill at 3.5 m.p.h. the correlation coefficient between the area under the curves so obtained and the total body weight loss was very high (more than 0.93), and there was also good correlation after sweating was partially suppressed by atropine. Short-period fluctuations were simultaneous and highly correlated between bilaterally symmetrical areas of skin. It is concluded that moisture loss from a single area of skin can be used to represent changes in the rate and pattern of sweating of the whole body.
EFFECT OF HYPOPHYSECTOMY AND HORMONE TREATMENT ON THE HEART–LUNG PREPARATION OF RATS
Authors: Korecky B. , Beznak M. , Korecka M.
Published: April 2011

Heart–lung preparations (h.l.p.) were made in normal rats, hypophysectomized rats, and in hypophysectomized rats treated with either growth hormone or thyroxine or both. While mean arterial pressure was kept constant at 100 mm Hg, the flow into the heart was increased stepwise until cardiac output did not rise any further (maximum cardiac output (m.c.o.)). Hypophysectomy substantially decreased the m.c.o., even when expressed per kilogram body weight. Thyroxine treatment alone or with growth hormone completely restored the m.c.o. to normal. However, when the m.c.o. was calculated per gram of left ventricle weight, it did not reach the normal level in any of the hypophysectomized rats investigated. Growth hormone, on the other hand, raised the stroke volume (expressed per gram of left ventricle) of hypophysectomized rats without affecting the rate of the heart.
EFFECT OF OXYGEN ON THE REGIONAL DISTRIBUTION OF VENTILATION AND PERFUSION IN THE LUNG
Authors: Holley H. S. , Dawson A. , Bryan A. C. , Milic-Emili J. , Bates D. V.
Published: April 2011

Xenon133 was used to measure distribution of ventilation and perfusion in the upper, middle, and lower lung zones of 12 upright healthy male subjects, at rest and during exercise, while breathing room air and after breathing 100% oxygen for 20 minutes. During the breathing of both air and 100% oxygen, ventilation and perfusion increased from the apex to the base of the lung, the differences between upper and lower zones becoming less pronounced during exercise. Oxygen breathing did not appear to affect distribution of regional ventilation or perfusion in normal upright man, either at rest or during exercise. This negative result is of importance in relation to the possible role in intact man of homeostatic mechanisms of adjusting perfusion and ventilation, which are sensitive to oxygen tension.