bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonin reuptake inhibitors fluoxetine and citalopram relax intestinal smooth muscle
Authors: Pacher Pal , Ungvari Zoltan , Kecskeméti Valéria , Friedmann Tamás , Furst Susanna
Published: April 2011

Selective serotonin reuptake inhibitor antidepressants (SSRIs) exert depressant effects on cardiac myocytes and vascular smooth muscle cells by inhibiting Ca2+ channels. We hypothesized that the SSRIs fluoxetine and citalopram affect the contractile activity of intestinal smooth muscle by interfering with Ca2+ entry and (or) signaling pathways. The effects of fluoxetine and citalopram on contractions of guinea-pig ileum longitudinal muscle-myenteric plexus preparations (LMMP) were compared with the effects of the voltage-operated Ca2+ channel inhibitors nifedipine and diltiazem. In a concentration-dependent manner, nifedipine, diltiazem, fluoxetine, and citalopram elicited relaxation of LMMPs contracted by electrical field stimulation (EC50 values of 4 × 107 M, 1.4 × 106 M, 1.4 × 105, and 6.8 × 106 M, respectively). Nifedipine, diltiazem, fluoxetine, and citalopram also relaxed LMMPs contracted with a depolarizing concentration of KCl (48 mM; EC50 values of 1.8 × 108 M, 1.4 × 107 M, 3.7 × 106 M, and 6.3 × 106, respectively), a response that could be reversed by increasing the extracellular Ca2+ concentration (2.530 mM). These data suggest that fluoxetine and citalopram elicit relaxation of intestinal smooth muscle, likely by inhibiting Ca2+ channel(s). This effect may be of clinical importance.Key words: fluoxetine (Prozac(r)), citalopram (Seropram(r)), nifedipine, diltiazem, L-type Ca2+ channels, intestinal smooth muscle.
Allosteric regulatory step and configuration of the ATP-binding pocket in atrial natriuretic factor receptor guanylate cyclase transduction mechanism
Authors: Sharma Rameshwar K , Yadav Prem , Duda Teresa
Published: April 2011

The atrial natriuretic factor (ANF) signal transduction mechanism consists of the transformation of the signal information into the production of cyclic GMP. The binding of ANF to its receptor, which is also a guanylate cyclase, generates the signal. This cyclase has been termed atrial natriuretic factor receptor guanylate cyclase, ANF-RGC. ANF-RGC is a single transmembrane-spanning protein. The ANF receptor domain resides in the extracellular region of the protein, and the catalytic domain is located in the intracellular region at the C-terminus of the protein. Thus, the signal is relayed progressively from the receptor domain to the catalytic domain, where it is converted into the formation of cyclic GMP. The first transduction step is the direct binding of ATP with ANF-RGC. This causes allosteric regulation of the enzyme and primes it for the activation of its catalytic moiety. The partial structural motif of the ATP binding domain in ANF-RGC has been elucidated, and it has been named ATP regulatory module (ARM). In this presentation, we provide a brief review of the ATP-regulated transduction mechanism and the ARM model. The model depicts a configuration of the ATP-binding pocket that has been experimentally validated, and the model shows that the ATP-dependent transduction process is a two- (or more) step event. The first step involves the binding of ATP with its ARM. This partially activates the cyclase and prepares it for the subsequent steps, which are consistent with its being phosphorylated and attaining the fully activated state.Key words: ANF, ANF-receptor guanylate cyclase (ANF-RGC), ATP, ATP-regulatory module (ARM).
Diversity of K+ channels in circular smooth muscle of opossum lower esophageal sphincter
Authors: Zhang Yong , Paterson William G
Published: April 2011

We previously demonstrated that a balance of K+ and Ca2+-activated Cl channel activity maintained the basal tone of circular smooth muscle of opossum lower esophageal sphincter (LES). In the current studies, the contribution of major K+ channels to the LES basal tone was investigated in circular smooth muscle of opossum LES in vitro. K+ channel activity was recorded in dispersed single cells at room temperature using patch-clamp recordings. Whole-cell patch-clamp recordings displayed an outward current beginning to activate at 60 mV by step test pulses lasting 400 ms (120 mV to +100 mV) with increments of 20 mV from holding potential of 80 mV ([K+]I = 150 mM, [K+]o = 2.5 mM). However, no inward rectification was observed. The outward current peaked within 50 ms and showed little or no inactivation. It was significantly decreased by bath application of nifedipine, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and iberiotoxin (IBTN). Further combination of TEA with 4-AP, nifedipine with 4-AP, and IBTN with TEA, or vice versa, blocked more than 90% of the outward current. Ca2+-sensitive single channels were recorded at asymetrical K+ gradients in cell-attached patch-clamp configurations (100.8 ± 3.2 pS, n = 8). Open probability of the single channels recorded in inside-out patch-clamp configurations were greatly decreased by bath application of IBTN (100 nM) (Vh = 14.4 ± 4.8 mV in control vs. 27.3 ± 0.1 mV, n = 3, P < 0.05). These data suggest that large conductance Ca2+-activated K+ and delayed rectifier K+ channels contribute to the membrane potential, and thereby regulate the basal tone of opossum LES circular smooth muscle.Key words: large conductance Ca2+-activated K+ channels, delayed rectifier K+ channels, patch-clamp recording, visceral smooth muscle.
Brain natriuretic peptide appears to act locally as an antifibrotic factor in the heart
Authors: Ogawa Yoshihiro , Tamura Naohisa , Chusho Hideki , Nakao Kazuwa
Published: April 2011

In addition to cardiac myocyte hypertrophy, proliferation and increased extracellular matrix production of cardiac fibroblasts occur in response to cardiac overload. This remodeling of the cardiac interstitium is a major determinant of pathologic hypertrophy leading to ventricular dysfunction and heart failure. Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones produced primarily by the atrium and ventricle, respectively. Plasma ANP and BNP concentrations are elevated in patients with hypertension, cardiac hypertrophy, and acute myocardial infarction, suggesting their pathophysiologic roles in these disorders. ANP and BNP exhibit diuretic, natriuretic, and vasodilatory activities via a guanylyl cyclase-coupled natriuretic peptide receptor subtype (guanylyl cyclase-A or GC-A). Here we report the generation of mice with targeted disruption of BNP (BNP/ mice). We observed focal fibrotic lesions in ventricles from BNP/ mice with a remarkable increase in ventricular mRNA expression of ANP, angiotensin converting enzyme (ACE), transforming growth factor (TGF)-β3, and pro-α1(I) collagen [Col α1(I)], which are implicated in the generation and progression of ventricular fibrosis. Electron microscopic examination revealed supercontraction of sarcomeres and disorganized myofibrils in some ventricular myocytes from BNP/ mice. No signs of cardiac hypertrophy and systemic hypertension were noted in BNP/ mice. In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP/ mice examined, accompanied by further increase of mRNA expression of TGF-β3 and Col α1(I). We postulate that BNP acts as a cardiocyte-derived antifibrotic factor in the ventricle.Key words: atrial natriuretic peptide, brain natiuretic peptide, cardiac fibrosis, guanylyl cyclase.
Transport energetics of the Na+ pump in Aplysia californica gut
Authors: Gerencser George A , Loo Stanley Y
Published: April 2011

Basolateral membranes of Aplysia californica foregut epithelia contain an ATP-dependent Na+ transporter (Na+ pump). Increased activity of the Na+ pump, coupled to luminal Na+/AIB symporter activity and basolateral membrane depolarization, changed the Na+ transport energetics across the basolateral membrane to a greater extent than the change in Na+ transport energetics across the luminal membrane.Key words: Na+ pump, Na+/K+-ATPase, Na+ electrochemical potential.
The in vivo toxicity of carbon tetrachloride and carrageenan on heart microsomes: analysis by Fourier transform infrared spectroscopy
Authors: Melin Anne-Marie , Perromat Annie , Deleris Gérard
Published: April 2011

We investigated the sensitivity of rat heart microsomes to free radical attack using Fourier transform infrared (FT-IR) spectroscopy. This physico-chemical method seemed a valuable technique: quite sensitive to changes in the vibrational spectra. The spectral variations observed between normal and treated rats were in great part due to reactive oxygen species that led to changes in protein conformation involving β-sheets, aggregation of proteins, and modification of protein synthesis. Carrageenan-induced inflammation slightly enhanced the total lipid content; rearrangement of acyl chains and accumulation of cholesterol esters and phospholipids also occurred in the treated rats. Carbon tetrachloride induced a decrease in both lipid and protein contents. The level of glucidic substrates was diminished with carbon tetrachloride and enhanced with carrageenan; these changes were due to metabolic interactions between cell components and drugs. FT-IR spectroscopy provided an accurate means to monitor, in rat heart, the in vivo effects of inflammatory and peroxidative damages, to discriminate and classify the affected cells, and to correlate the findings with known physiological and biochemical data in close relationship with metabolic disruptions induced by the two xenobiotics. Key words: heart microsomes, carbon tetrachloride, carrageenan, peroxidation, FT-IR.
Differential effects of phenobarbital on the constitutive and inducible expression of P450 2B and 3A subfamilies in sheep tissues
Authors: Dupuy Jacques , Larrieu Gilberte , Braun Jean Pierre , Alvinerie Michel , Galtier Pierre
Published: April 2011

The activity and expression of cytochromes P450 were determined in liver, kidneys, lungs, duodenum, jejunum, ileum, and caecum of adult Lacaune sheep. High expression of total P450, benzphetamine and erythromycin demethylase activities, and P450 2B isoforms, as two distinct proteins that were detected and called P4502 Bm and P4502 Bx, was found in the lungs (in addition to liver). By contrast, the P450 3A subfamily was only expressed in liver and duodenal mucosa of untreated sheep. Phenobarbital (PB) treatment led to significant increases in all measured hepatic parameters and in total P450 of each investigated organ with the exception of ileum and caecum. Benzphetamine demethylase activity increased in liver and kidneys, correlating with the expression of the two P450 2B proteins, which were also induced in duodenum and ileum. By contrast, benzphetamine demethylase activity and expression of the P450 2B isoforms in lungs were unchanged by PB treatment. Erythromycin demethylation activity and P450 3A subfamily expression was increased only in liver of PB-treated sheep.Key words: phenobarbital, sheep, cytochromes P450, inducibility, tissue distribution.
Thiopental enhances human platelet aggregation by increasing arachidonic acid release
Authors: Kitamura Rie , Hirakata Hideo , Okuda Hiroto , Sato Masami , Toda Hiroshi , Nakamura Kumi , Hatano Yoshio , Urabe Nobukata , Fukuda Kazuhiko
Published: April 2011

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30300 µM). Platelet activation was induced by adenosine diphosphate (ADP, 0.515 µM), epinephrine (0.120 µM) arachidonic acid (0.51.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2(STA2, 30500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 µM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental ([Formula: see text]100 µM). Thiopental ([Formula: see text]100 µM) also increased the TXB2formation induced by ADP and epinephrine. Thiopental (300 µM) increased ADP- and epinephrine-induced3H-AA release. Thiopental (300 µM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]iin the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.Key words: barbiturates, anesthetics, eicosanoids, phospholipase.
The innervation of the human antro-pyloric region: Organization and composition
Authors: Smith V C , Dhatt N , Buchan A MJ
Published: April 2011

Although the composition of the gastric innervation has been determined in animal models, relatively little known about the innervation of the human antro-pyloric region. We used immunocytochemical techniques to establish the localization and co-expression of neuropeptides and nitric oxide in the human antrum and upper duodenum. Our results demonstrate the existence of a clearly defined submucosal plexus in the antral region that is absent in rats and guinea pigs. The abundant innervation of the lamina propria contains 3 major nerve populations: VIP- and NOS-, SP- and CGRP-, and GRP-immunoreactive. For the first time, NOS-containing nerve fibers were observed throughout the length of the antral glands. Within the antrum somatostatin was confined to endocrine cells, however, at the pyloric sphincter both enteric plexi contained immunoreactive neurons and nerve fibres. Within the pyloric sphincter CGRP- and SP-immunoreactive fibres were significantly increased, correlating with the presence of large ganglia in the submucosal plexus. In conclusion, the organization and composition of the innervation of human antro-pylorus differed substantially from that reported in other mammals. The presence of an abundant mucosal innervation paralled by a well-defined submucosal plexus indicates that the functional regulation of the gastricpyloric region will be distinct from that of smaller animal models.Key words: gastric innervation, pyloric sphincter, neuropeptides, nitric oxide, somatostatin.
Sequence and chromosomal assignment of a human novel cDNA: similarity to gamma-aminobutyric acid transporter
Authors: Gong Yuewen , Zhang Manna , Cui Li , Minuk Gerald Y
Published: April 2011

Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian brain. Although initially thought to be confined to the central nervous system, GABAergic activity has also been described in other tissues throughout the body. In the present study, we report the cloning and localization of human GABA transporter cDNA and document its expression in various human tissues. A human liver cDNA library was initially screened by a32P-labeled murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was cloned by employing Marathon-Ready(tm) human kidney cDNA. The human GABA transporter cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains (TMs). Search of published sequences revealed high homology with rat GAT-2, murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the human GABA transporter is expressed strongly in the kidney and to a lesser extent in the liver and brain. The sequence was well matched with human chromosome 12p13.3, suggesting the human GABA transporter contains 14 exons. The above findings confirm the existence of and further characterize a specific GABA transporter in human tissues.Key words: sequence, chromosome, GABA, GABA transporter.
Effect of altered physical loading on bone and muscle in the forearm
Authors: MacIntyre Norma J , Bhandari Mohit , Blimkie Cameron J , Adachi Jonathan D , Webber Colin E
Published: April 2011

Cast immobilization of injured forearms is common clinical practice yet little is known about the effect of reduced skeletal loading in the absence of pathology. This study reports the changes in the forearms of nine healthy young adults owing to six weeks in a plaster cast followed by 1 year of either habitual activity or a strengthening program. Both groups exhibited similar patterns of change in wrist mobility, forearm muscle strength, and bone variables. Because of small sample size and poor compliance with the exercise protocol, no conclusions can be drawn about the effect of exercise. In all subjects, reduced loading caused a decrease in wrist mobility (p < 0.02) and grip strength (p = 0.01) with full recovery following 3 months of remobilization. Six months after removing the cast, bone size was reduced in the middle region of the radius (p = 0.02) and recovered after 1 year of remobilization. Given that radial bone mass tended to decrease while bone density was unchanged, we conclude that the effect of casting was modulated by changes in gross bone morphology rather than in material characteristics.Key words: bone mass, muscle strength, physical loading, radius, young adults.
The process of cardiorespiratory autoresuscitation in intact newborn rats
Authors: Saiki Chikako , Ikeda Mizuho , Nishikawa Toshimi , Tanimoto Takeshi , Yoshida Shinki , Matsumoto Shigeji
Published: April 2011

To examine the process of spontaneous autoresuscitation and the recovery of the hypoxic ventilatory response (HVR) after prolonged anoxia, we monitored respiratory frequency (f, by body plethysmography) and heart rate (HR, by ECG) in intact newborn rats (n = 12, day 24) before, during, and after 100% N2 exposure. The rat before anoxia showed signs of HVR: f changes at acute hypoxia (10% O2) and hyperoxia (100% O2). During anoxia, the spontaneous respiratory movement "gasping" appeared for 21 min (mean). At O2 restoration (with 100% O2), gasping stopped and no respiratory flow was detected for 1 min. One rat failed to autoresuscitate and had heart arrhythmia during the transient apnea, but 11 rats recovered respiration after the HR acceleration. Despite the successful autoresuscitation, the rats did not show HVR at 10 min into the recovery period and the recovery of HVR required more than 30 min. The results indicate that O2 inhalation is useful to trigger autoresuscitation even when the rat has already been in a state of profound hypoxic depression, but the rat becomes transiently insensitive to HVR after autoresuscitation. We estimate that reform of the respiratory control system in newborn rats is not yet firmly established to track HVR early in the recovery phase after prolonged anoxia.Key words: anoxia, hypoxic ventilatory response, cardiopulmonary resuscitation (CPR), sudden infant death (SID).
The effect of adrenalectomy on the cardiac response to subacute fetal anemia
Authors: Jonker Sonnet S. , Scholz Thomas D. , Segar Jeffrey L.
Published: April 2011

The mechanisms that stimulate fetal heart growth during anemia are unknown. To examine the hypothesis that adrenal hormones contribute to this process, we determined the effects of adrenalectomy (Adx) on heart growth and the activation of cardiac mitogen-activated protein kinases (MAPKs) in the presence and absence of fetal anemia. To identify mechanisms contributing to the initiation of cardiac growth, the duration of anemia was limited to a period shorter than that previously described to result in increased cardiac mass. Four groups of fetal sheep were studied (Adx-Anemic, Adx-Control, Intact-Anemic, Intact-Control). Anemia was created by daily controlled hemorrhage for 5 days; hearts were collected for analysis at 133 d gestation (term 145 d). Cardiomyocyte morphometry, immunohistochemistry for Ki-67 (proliferation marker), and Western blotting for protein levels of MAPKs and proliferating cell nuclear antigen (PCNA) were performed. Blood pressure, heart rate, heart weight-to-body weight ratio, and cardiomyocyte length and width remained similar among groups throughout the study. PCNA levels in the Adx-Anemic group were twice as high as in any other group (both ventricles, p < 0.05). Levels of phosphorylated extracellular signal-regulated kinase (ERK) were ~60% higher in the Intact-Anemic and Adx-Anemic groups, compared with the Intact-Control and Adx-Control groups (p < 0.02). These results suggest that adrenal hormones may attenuate fetal cardiomyocyte proliferation in response to anemia (as evidenced by the increased PCNA in Adx-Anemic fetuses) and that phosphorylation of myocardial ERK results from fetal anemia, irrespective of the status of the fetal adrenal gland.
Effect of celecoxib on the antihypertensive effect of losartan in a rat model of renovascular hypertension
Authors: Boshra Vivian , El Wakeel Gehan Abdel Hamid , Nader Manar A
Published: April 2011

Certain nonsteroidal anti-inflammatory drugs have been reported to elevate blood pressure in some hypertensive patients, who are either untreated or treated with antihypertensive agents. This study was undertaken to determine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the antihypertensive effects of the angiotensin II type 1 receptor (AT1) antagonist, losartan potassium. We studied the effect of oral treatment with losartan (30 mg/kg), celecoxib (3 mg/kg), and their combination on the mean arterial blood pressure (MAP), plasma renin activity (PRA), and plasma prostaglandin E2(PGE2) in male Sprague–Dawley rats with renovascular hypertension (RVH) induced by partial subdiaphragmatic aortic constriction. Treatment was continued for 7 days after aortic coarctation. Aortic coarctation led to significant increases in the MAP, PRA, and plasma PGE2. In RVH rats, losartan treatment caused a significant decrease of MAP with a significant increase in both plasma PGE2and PRA. Celecoxib caused a nonsignificant change in MAP with a significant decrease in the raised levels of plasma PGE2and PRA. Concomitant administration of celecoxib and losartan did not significantly affect the lowering effect of losartan on MAP with a subsequent significant decrease in the plasma PGE2and PRA in RVH rats. Therefore, celecoxib could be used in renin-dependent hypertensive patients who receive losartan, without fear of a rise in their blood pressure.
Central mechanism underlying pressor and bradycardic effect of intracerebroventricularly injected arachidonic acid
Authors: Yalcin Murat
Published: April 2011

The aim of the current study was to determine the central cyclooxygenase (COX) pathway and central thromboxane signaling in the cardiovascular effects evoked by arachidonic acid (AA). As a main control for the study, different doses of AA (75, 150, or 300 µg) were administered intracerebroventricularly (i.c.v.). Centrally injected AA dose- and time-dependently increased mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. The maximal cardiovascular effects of AA were observed at min 10 of the injection and lasted almost 30 min. To investigate the central mechanism of the AA-induced cardiovascular effect in conscious normotensive animals, pretreatment with nonselective COX inhibitor indomethacin (200 µg; i.c.v.), thromboxane A2 (TXA2) synthesis inhibitor furegrelate (250 or 500 µg; i.c.v.), or TXA2 receptor antagonist SQ-29548 (8 or 16 µg; i.c.v.) was carried out 15 min before AA (150 µg; i.c.v.) injection. While indomethacin completely prevented the pressor and bradycardic responses to AA, furegrelate and SQ-29548 attenuated these effects in part in awake normotensive rats. In conclusion, these findings suggest that the pressor and bradycardic cardiovascular effects of centrally injected AA are dependent on COX activity being totally central and the TXA2 signaling pathway being subsequently central, at least in part.
THE EFFECT OF ACTH, CORTISONE, DESOXYCORTICOSTERONE, AND ACTH PLUS THYROID ON THE AMYLOLYTIC ACTIVITY OF THE PANCREAS IN HYPOPHYSECTOMIZED AND INTACT RATS
Authors: Nishikawara Margaret T. , Hawkins Rosemary D. , Haist R. E.
Published: April 2011

After hypophysectomy the pancreas was reduced in weight and its amylolytic activity decreased. This activity was restored partially by the administration of ACTH or by cortisone, but desoxycorticosterone was without significant effect. When both ACTH and desiccated thyroid were given together, complete restoration of pancreas weight per unit of body weight was achieved but amylolytic activity, though significantly increased over the levels found in the hypophysectomized animals, was still below that found in intact pair-fed controls. It appears that part of the pituitary influence in maintaining the exocrine pancreas is mediated through the adrenal cortex and that the 11-oxygenated steroids are involved in this effect.
DECOMPRESSION MORTALITY RELATED TO LUNG OEDEMA AND TENSION PNEUMOTHORAX
Authors: Topliff E. D. L.
Published: April 2011

Two groups of female hamsters (150 ± 50 g) were subjected to decompression from various pressures above atmospheric to a final pressure of 1 atmosphere. In one of these groups the wet:dry lung weight ratio was determined. Elevation of this ratio was taken as evidence of lung oedema. In the other group a postmortem test for valvular rupture of the lungs was applied. This test is based on the principle that air passing from a ruptured lung into the intrapleural space cannot reenter the lung, owing to valvular action of the lung tissue at the site of rupture. The results suggest that two modes of death may result from decompression: rapid death associated with tension pneumothorax, and relatively slow death associated with lung oedema. The relative incidence of tension pneumothorax, as compared to lung oedema, increases with increasing severity of decompression.
VESTIBULAR STIMULATION AND FOREARM BLOOD FLOW
Authors: Sunahara F. A. , Johnson W. H. , Taylor N. B. G.
Published: April 2011

Forty-six adult male subjects have been exposed to strong vestibular stimulation produced by controlled cyclic nodding of the head while being rotated in the horizontal plane on a turntable at constant angular velocity. Forearm blood flow was measured with a mercury-in-rubber strain gauge plethysmograph standardized against a conventional plethysmographic technique. There was wide variability among the subjects in the amount of vestibular stimulation needed to cause nausea just short of emesis. Motion sickness, when unequivocal, was accompanied by increased blood flow in the forearm and nearly always by an increase in the circumference of the forearm when venous flow was not occluded. Resistant subjects, in whom motion sickness was either minimal or not apparent, showed either no increase in forearm blood flow or increases that were equivocal. It is concluded that increased muscle blood flow may now be added to antidiuresis, nausea, pallor, and sweating, as a physiological response common to the vasovagal syndrome and to motion sickness caused by vestibular stimulation. A possible explanation of the results and their relation to aviation are discussed.
A STUDY OF BLOOD PRESSURE RESPONSES DURING HYPOTHERMIA IN HYPOPHYSECTOMIZED RATS
Authors: Hunter J. , Haist R. E.
Published: April 2011

When intact rats are cooled, the blood pressure is well maintained down to a body temperature of 22 °C, below which it rapidly falls. When hypophysectomized rats are cooled the reduction in blood pressure bears a linear relation to the body temperature. The infusion of Pitressin into hypophysectomized animals during the cooling procedure restores the blood pressure – body temperature relationship to that seen in intact rats. This occurs whether or not the renal vessels are ligated and hence appears to be independent of renal factors. However, when the kidneys are exteriorized and warmed and, at the same time, Pitressin is infused into the hypophysectomized cooled rats, there is an excellent maintenance of blood pressure at the lower body temperatures, the blood pressure being 110 mm Hg when the body temperature is 12 °C. Infusions of angiotensin II and of renin also are effective in maintaining blood pressure in hypothermic hypophysectomized animals. This effect of renin is not influenced by exteriorizing and warming the kidneys, hence the enhancement of the effect of Pitressin by this procedure is not a consequence of the warming alone. Warming the exteriorized kidneys may release some factor or cause some change which, in the presence of Pitressin, effectively maintains blood pressure at low body temperatures.
TOLERANCE TO THE INDUCTION OF CARDIAC ARRHYTHMIAS BY ADRENALINE IN CYCLOPROPANE-ANAESTHETIZED DOGS
Authors: MacCannell Keith L. , Dresel Peter E.
Published: April 2011

Long-continued maintenance of anaesthesia with cyclopropane has been reported to inhibit the induction of arrhythmias by adrenaline through an "adrenolytic effect". This effect is not observed in dogs in which anaesthesia is maintained with 20% cyclopropane, although a tachyphylaxis to the arrhythmic effect of adrenaline develops with repeated injections of the amine. Tachyphylaxis to the induction of multifocal and fibrillatory ventricular rhythms by adrenaline occurs less readily in the thiopental-treated animal. An "adrenolytic effect", independent of the number of injections of adrenaline, is apparent at higher concentrations of cyclopropane. The latter observation may explain in part the finding that cardiac arrhythmias are demonstrable within a limited range of cyclopropane concentrations.
ABSENCE OF EFFECT OF BOVINE GROWTH HORMONE ON BLOOD SUGAR OF HOUSSAY DOGS
Authors: Sirek Anna , Schoeffling Karl , Webster Monica , Sirek Otakar V.
Published: April 2011

A highly purified growth hormone preparation (Wilhelmi) was tested for its hypoglycemic activity in four fasting, hypophysectomized–depancreatized dogs (Houssay dogs) maintained without exogenous insulin for 2–4 weeks. A single intravenous injection of growth hormone, 5 mg per kg body weight, had no effect on blood sugar over a period of 6 hours. It was concluded that highly purified growth hormone has no hypoglycemic effect in the absence of biologically active insulin.
CHANGES IN PLASMA TRIGYLCERIDE CONCENTRATION FOLLOWING THE INTRAVENOUS ADMINISTRATION OF GLUCOSE
Authors: Perry W. F. , Corbett B. N.
Published: April 2011

The intravenous administration of glucose is followed by a fall in plasma concentration of triglyceride which is maximal 30 to 60 minutes postinjection. This fall in triglyceride is associated with an increase in the ability of the plasma to bring about lipolysis of triglyceride in vitro. This increase in lipolytic activity of plasma following glucose administration could partially explain the fall in the circulating level of triglyceride noted after glucose administration. This effect is present in both males and females but is more pronounced in the former.
THE ACTION OF A PROTEOLYTIC ENZYME FROM ASPERGILLUS ORYZAE ON COMPONENTS OF THE BLOOD CLOTTING SYSTEM
Authors: Monkhouse Frank C. , Daramola Florence , Gillespie R. J.
Published: April 2011

CA.7, a highly purified proteolytic enzyme from Aspergillus oryzae, acts on a number of the coagulation factors. In low concentrations, immediate action is to decrease the recalcified clotting time. The evidence, as furnished by experiments on a prothrombin fraction, is that it does this by converting prothrombin to thrombin. In this regard its action is similar to that of thromboplastin. During incubation, especially with increasing concentrations, it destroys prothrombin and fibrinogen, and plasma becomes incoagulable. It destroys normal plasma antithrombin but, paradoxically, generates a thrombin–fibrinogen inhibiting activity by its proteolytic action on fibrinogen in plasma.
STATIC ELASTIC MODULUS OF THE TURKEY AORTA
Authors: Speckmann Elwood W. , Ringer Robert K.
Published: April 2011

A method was described for the determination of the static elastic modulus for thoracic and abdominal aortas of the turkey. Love's equation was rearranged for calculation of the static elastic modulus as a function of volume. The elastic moduli of thoracic and abdominal aortas of untreated mature male Broad Breasted Bronze turkeys were in the neighborhood of 2.26 ± 0.11 and 9.55 ± 0.30 × 105 dynes/cm2 respectively in the normal physiological systolic blood pressure range. This difference became more pronounced at higher pressures. The data obtained support the concept that different connective tissue elements are primarily responsible for the elastic properties of arterial blood vessels at different pressure ranges. The addition of beta-amino-propionitrile (BAPN) to the ration tended to decrease, whereas the addition of ascorbic acid to the ration tended to elevate the elastic modulus. Reserpine fed in conjunction with BAPN in the ration did not correct the lowering action of BAPN on the elastic moduli of abdominal or thoracic aortas. Heat tended to elevate the elastic modulus of the aorta. Again, these effects became more significant at elevated pressures.
EFFECTS OF E-A.C.A. IN SPONTANEOUS HEMORRHAGE DUE TO STRESS WITH ANTICOAGULANTS IN RATS
Authors: Lucas Oscar N. , Jaques L. B.
Published: April 2011

Epsilon aminocaproic acid was used in an attempt to prevent the hemorrhagic manifestation that occurs when a stressor agent is combined with anticoagulant in rats. Groups of rats were subjected to restraint or lysergic acid diethylamide (L.S.D.) and then given an anticoagulant, phenylindanedione, for 10 days. Other groups were subjected to twice-daily injections of physiological saline, during the 10 days of experiment, simultaneously with the anticoagulant. Close observations were made to evaluate any hemorrhagic manifestation. Postmortem examination was performed on the rats that died during the experiment, and on the survivors which were sacrificed upon conclusion of the 10 day period. Restraint, L.S.D., and twice-daily injections of physiological saline subcutaneously all caused spontaneous hemorrhage in anticoagulant-treated animals. The administration of E-A.C.A. by subcutaneous injection or in the drinking water during the 10 day duration of the experiment did not prevent the high incidence of hemorrhage in the groups when the stressor agent was combined with anticoagulant.
THE AMELIORATIVE EFFECTS OF HEPARIN AND DEPOLYMERIZED HYALURONATE ON DECOMPRESSION SICKNESS IN RATS
Authors: Philp R. B.
Published: April 2011

The protective effects in decompression sickness of heparin, partially depolymerized hyaluronate (PDHA, a substance reported to have antilipaemic properties), and bishydroxycoumarin have been studied by a standardized compression–decompression technique in rats. Bishydroxycoumarin did not afford any significant degree of protection even at dose levels which prolonged the prothrombin time as much as five times normal. Heparin, however, significantly reduced the incidence of "bends" in rats at a dose which only briefly prolonged the whole-blood clotting time, and significantly reduced both the incidence and the severity at higher dose levels. PDHA produced the most marked reduction in both incidence and severity at dose levels which did not significantly alter the whole-blood clotting time. These protective effects were absent when heavy, fat rats were used, and when the compounds were administered before the compression (i.e. more than 2 hours before the actual evaluation of signs of the bends). In view of these results it is postulated that anticoagulation per se has little beneficial effect in treating the bends; the protection afforded by these mucopolysaccharides may be related to their lipaemia-clearing activity.
HYPOPHYSEAL–ADRENAL ACTIVITY IN COMBINED HUMAN FOETAL TISSUE CULTURES
Authors: Stark E. , Gyévai A. , Szalay K. , Ács Zs.
Published: April 2011

Experiments carried out with human foetal hypophysis or adenohypophysis cultured in combination with adrenal tissue supplied evidence that the human foetal adrenal possesses the potentiality to secrete hydrocortisone, and the human foetal hypophysis to secrete ACTH, and, further, that the hypophysis continues to produce ACTH at a low level without stimulation by the hypothalamus, at least for some time.ACTH added when hydrocortisone production had already been falling for several days invariably increased adrenocortical hormone production. Remarkably, this production reached its peak not on the day of addition, but 2 to 4 days later, although the cultures had been washed daily and no fresh ACTH had been introduced.
CORONARY FLOW, BLOOD PRESSURE, AND HEART RATE DOSE–RESPONSE CHANGES AFTER NITROGLYCERIN ADMINISTRATION
Authors: Melville K. I. , Gillis R. A. , Sekelj P.
Published: April 2011

Changes in left circumflex coronary flow, femoral blood pressure, and heart rate (ECG-Lead II) were recorded simultaneously in pentobarbitalized artificially respired open-chest dogs. A gated sine wave electromagnetic flowmeter was used for coronary flow measurements. After intravenous nitroglycerin (glyceryl trinitrate) administration in six satisfactory experiments, changes in dose–response patterns were studied. (1) Doses of 0.1 μg/kg were ineffective; doses of 1.0, 10, and 100 μg/kg induced in 10 to 15 seconds maximal increases in mean coronary flow averaging 22, 65, and 100%, respectively; blood pressure concurrently decreased showing a maximum fall (in 20 to 25 seconds) associated with reflex tachycardia; a transient initial increase in pulse pressure also occurred. (2) Coronary flow subsequently decreased, reaching below-control values; the magnitude of this decrease appeared to be related to the degree of fall in blood pressure and to the reflex tachycardia; and pulse pressure markedly decreased below the control values. (3) After intravenous injections of pentobarbitone sodium (1 and 10 mg/kg) brief initial (within 10 seconds) dose-related increases in coronary flow were also observed but associated with less-marked blood pressure decreases and no significant changes in either heart rate or pulse pressure.
THE USE OF Cr51 AS A CRITERION OF THYMOCYTE REGENERATION AFTER WHOLE BODY X-IRRADIATION
Authors: Vittorio P. V. , Baker P. J. , Dziubalo-Blehm S.
Published: April 2011

The uptake of Cr51 chromate by thymocytes in vitro after whole body X-irradiation can be used as a sensitive quantitative criterion not only for the evaluation of early radiation damage to these cells but also as a measure of later regeneration. The development of the radiation lesion is characterized by a reduction in the in vitro uptake of Cr51 and the later regeneration of new cells by an increase in Cr51 uptake which is probably due to increased uptake of Cr51 by the young newly formed cells in the damaged tissue which is proliferating in an attempt to repair the damage. The return of the Cr51 uptake to normal is an indication of the time required for the cell population (ratio of young to older cells) to return to normal. By this technique the effect of different doses of X-irradiation on the regeneration of thymocytes has been demonstrated. Treatment with AET before whole body X-irradiation (400 r) indicated that less regeneration was necessary but the recovery time remained unchanged. Age differences produced a change in the extent of repair or regeneration but no change in recovery time.Spermatozoa showed evidence of early damage after whole body X-irradiation. This damage increased with time with no evidence of increased regeneration or repair.
SITES OF CALCIUM ABSORPTION AND THE CALCIUM CONCENTRATION OF GUT CONTENTS IN THE DOG
Authors: Cramer C. F.
Published: April 2011

Physiological concentrations of calcium were measured in the lumen of the intestine of dogs which had been fed low, normal, or high levels of calcium. The rates of Ca absorption from duodenal, jejunal, or ileal Thiry-Vella fistulae were also determined. These data demonstrate that high Ca concentrations usually exist in the intestinal tract, and that the concentration in the lumen is directly affected by dietary level of Ca. The rate of calcium absorption per cm length of duodenum was almost double that in the jejunum or ileum, but the estimated effective Ca absorption in the whole ileum (744 mg/6 hours) exceeded that in the jejunum (144 mg/6 hours) and that in the duodenum (36 mg/6 hours).
ON THE MECHANISMS WHEREBY EDTA, EGTA, DPTA, OXALATE, DESFERRIOXAMINE, AND 1,10-PHENANTHROLINE AFFECT CONTRACTILITY OF RAT UTERUS
Authors: Daniel E. E. , Irwin John
Published: April 2011

The effects of EDTA on rat uterine horns were studied and found to consist of contraction followed by relaxation, and inhibition of subsequent contraction in response to acetylcholine. An hypothesis was formulated to explain these actions. The contraction is attributed to complexing and consequent decrease in the activity of magnesium in or near the membrane, accompanied by unstabilization of the membrane following removal of calcium from sites at which it exerts a stabilizing action. The relaxation is attributed to similar complexing of membrane calcium bound to other sites from which it is released during excitation to cause contraction. Na4EDTA was much more effective in evoking contractions than Na2EDTA; this is attributed to the competition between hydrogen and magnesium.Experiments in which ions in the bathing medium were varied supported this general hypothesis. Furthermore, MgEDTA was found to produce only relaxation, while CaEDTA was found to produce little or no effect; mixtures had intermediate effects. The calcium-depleted membrane was found to compete effectively with CaEDTA for its calcium. Similar studies were carried out with DTPA (diethylenetriaminepentaacetic acid) and similar results obtained. DTPA was more dependent than EDTA on a high pH, as expected from the greater affinity of this material for hydrogen ions. EGTA (ethylene bisglycol (β-aminoethylether) tetraacetic acid), a substance with equivalent ability to complex calcium and less ability to complex magnesium relative to EDTA or DTPA, was ineffective in evoking contraction unless magnesium was omitted from the medium; however, it did inhibit responses to subsequent acetylcholine. None of these complexing agents produced significant contractions when strontium was substituted for calcium.Other complexing agents unrelated to EDTA were studied as well. Desferrioxamine (DFO) caused contractions when added at a pH of 9 or more. It had little inhibitory action on acetylcholine-evoked contractions. Oxalate was relatively ineffective in evoking contraction or inhibition of responses to acetylcholine. Both these sets of findings are compatible with the hypotheses for EDTA when considered in the light of the complexometric characteristics of DFO and oxalate. 1,10-Phenanthroline, which complexes neither magnesium nor calcium effectively, evoked no contractions, but did inhibit contractions in response to other agents by a mechanism apparently unrelated to calcium.
THE EFFECT IN MAN OF CHANGES IN INTRATHORACIC PRESSURE ON CARDIAC OUTPUT
Authors: O'Neill A. , Valet L. , Cudkowicz L.
Published: April 2011

Left ventricular output [Formula: see text] was measured in 18 patients by the dye dilution technique during breath holding for 20 seconds at the mid-tidal level and at a mean intraoesophageal pressure (lop) of −2.97 mm Hg. [Formula: see text] was 4.86 l./minute, cardiac index (CI) 3.47 l./minute m2, and stroke volume 75 ml. Increments of lop during phase 2 of Valsalva's manoeuver in the range of 12 to 35 mm Hg led to a significant stepwise decrease in [Formula: see text], CI, and stroke volume. Extrapolation back to zero lop indicated that [Formula: see text] decreases by 0.1 l./minute with each rise of 1 mm Hg. During phase 4, or the "overshoot" phase, a significant increase in [Formula: see text], CI, and stroke volume was found which could not be related to temporary hyperventilation or decrease in lop characteristic of that phase. Reduction in lop during Mueller's manoeuver in 10 observations reached the range of −3 to −25 mm Hg. After an initial decrease in [Formula: see text] by 13.0% in the range of −3 to −7 mm Hg of lop, mean [Formula: see text] increased by approximately 40% with progressive decreases of 6 mm Hg Iop. Statistical significance could, however, not be established for the [Formula: see text] changes during acute decreases in Iop.
THE TEMPERATURE RESPONSE OF THE MALE RAT TO TREADMILL EXERCISE, AND THE EFFECT OF ANTERIOR HYPOTHALAMIC LESIONS
Authors: Thompson G. E. , Stevenson J. A. F.
Published: April 2011

Male rats exercised on a motor-driven treadmill at a speed of 4.6 meters/minute showed an increase in colonic temperature until it reached a level (39.2–39.5 °C) at which peripheral vasodilatation, as measured by change in skin temperature, occurred in the feet and tail. The colonic temperature then remained at this level above the resting temperature for the duration of exercise. Increasing (6.2 meters/minute) or decreasing (3.2 meters/minute) the speed of exercise resulted in more or less vasodilatation respectively, but did not change appreciably the level at which colonic temperature was regulated during exercise. The colonic temperature at which peripheral vasodilatation first occurred appeared to be a "critical" temperature, being altered by bilateral lesions in the preoptic and anterior hypothalamic areas of the brain.
THE LIPOTROPIC ACTION OF COLD: 2. THE INFLUENCE OF COLD AND CHOLINE DEFICIENCY ON SERUM LIPIDS OF RATS AT DIFFERENT INTAKES OF DIETARY METHIONINE
Authors: Radomski M. W. , Wood J. D.
Published: April 2011

The effect of exposure of rats to cold for a 10-day period on the concentration of serum lipids in control and choline-deficient animals was studied at four dietary intakes of methionine. Changes in total lipids, total and free cholesterol, phospholipid, and triglyceride levels were measured.In control (choline-fed) animals, phospholipid, cholesterol, and the ratio of free:ester cholesterol levels were not altered by cold exposure, but a marked decrease (25–30%, P < 0.01) in the levels of total serum lipids occurred. This was a result of a 45–70% decrease in triglyceride levels. The concentration of the triglyceride-rich low-density lipoproteins (Sf10–400) in the serum fell in the cold-exposed animals as indicated by lowered triglyceride:cholesterol ratios.Although cold exposure prevented fatty livers in choline-deficient rats at high methionine intakes, it did not prevent the characteristic decrease in serum lipids found in choline deficiency at any of the methionine intakes studied. Decreases in total lipids (20–40%), triglyceride (10–50%), cholesterol (15–40%), and phospholipids (15–40%) were found. It was concluded that the ability of cold exposure to overcome choline deficiency is limited, apparently, to the fatty liver syndrome and has no effect on the decreased serum lipid levels.
THE EFFECT OF ETHER ANESTHESIA ON PLASMA CORTICOSTEROIDS AND HEMATOLOGIC RESPONSES
Authors: Cann M. C. , Zawidzka Z. Z. , Airth J. M. , Grice H. C.
Published: April 2011

Blood samples taken from the aorta at the iliac bifurcation of ether-anesthetized rats were similar in plasma corticosteroids, white blood count, and differential count to those taken from rats by decapitation or by ether anesthesia and decapitation. These values were not affected by ether anesthesia of less than 2 minutes duration. The values were affected by continuous ether exposure of more than [Formula: see text] minutes duration up to 96 minutes.