bluuebunny/crossref_metadata_2025 huggingface dataset:
Cysteine proteinase inhibitor in eccrine sweat is derived from sweat gland
Authors: Yokozeki H. , Hibino T. , Takemura T. , Sato K.
Published: December 2017

Although cysteine proteinases have been reported to be present in human eccrine sweat, their endogenous inhibitors, cysteine proteinase inhibitors (CPIs), have remained unstudied. We now present evidence that CPIs are indeed a true ingredient of human eccrine sweat. Sweat induced in sauna was collected over a Vaseline barrier placed on the skin to minimize epidermal contamination. The absence of major epidermal contamination of the sweat was further ensured by monitoring an epidermal marker, high-molecular-mass aminopeptidase. Sweat CPI was purified sequentially by chromatography with Sephacryl S-200, carboxymethylated papain-Sepharose, and anion-exchange Mono Q fast-protein liquid chromatography columns. Sweat CPI has a molecular mass of approximately 15 kDa, is stable for temperature (up to 80 degrees C) and pH (from 3 to 10), and inhibits papain, ficin, and sweat cathepsin B- and H-like enzymes. Sweat CPI may be of sweat gland origin because 1) the rate of CPI output in sweat (CPI concentration x sweat rate) is constant over 45 min; 2) antibody against epidermal CPI, which cross-reacts with sweat CPI, localized immunoreactivity in the sweat duct; 3) CPI activity was present in the glandular extracts of control and methacholine-stimulated (for 1 h in vitro) human sweat glands; and 4) the peaks of CPI activity in the glandular extract and sweat CPI were both eluted (by high-pressure liquid chromatography) at around 15 kDa. Sweat CPI may be very similar to epidermal CPI (which belongs to the stefin family of CPIs) because of many shared characteristics. The identity and function of sweat CPI remain to be studied.
Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism
Authors: Billington C. J. , Briggs J. E. , Grace M. , Levine A. S.
Published: December 2017

Our objective was to find out if central injection of neuropeptide Y (NPY) would alter brown fat thermogenesis and white fat lipoprotein lipase activity. The following three groups of Sprague-Dawley rats received five injections over 24 h into the right lateral ventricle: 1) NPY (5 micrograms/injection) and ad libitum food; 2) NPY (5 micrograms/injection) and food restricted to control intake; 3) saline injection and ad libitum food. The NPY ad libitum-fed group consumed more food than the saline controls or NPY food-restricted animals. Brown fat thermogenic activity, assessed by GDP binding, was decreased relative to saline controls in both NPY-treated groups. White fat lipoprotein lipase activity was greatly increased in both NPY treatment groups compared with saline controls. The NPY effects on brown and white fat were not explained by measures of serum insulin, glucagon, glucose, or other metabolites. In a follow-up experiment, we asked whether food was necessary for expression of the NPY effects. Brown fat mitochondrial GDP binding indicated NPY effect even when no food was ingested. We conclude that intracerebroventricular administration of NPY promotes white fat lipid storage and decreases brown fat thermogenesis in addition to its known effect of stimulating food intake.
Chemical regulation of cerebral blood flow in turtles
Authors: Davies D. G.
Published: December 2017

This study was performed to test the effect of the chemical composition of the blood on cerebral blood flow (CBF) regulation in turtles. The CBF response to increases in arterial PCO2 (PaCO2) (hypercapnia) was measured during normoxia and anoxia in anesthetized freshwater turtles Pseudemys scripta. The radioactive-microsphere technique was used to measure CBF. CBF increased with increases in PaCO2. The sensitivity of the CBF response to hypercapnia (delta CBF/delta PaCO2) was 0.68 ml.min-1.100 g-1. Torr-1 during normoxia. delta CBF/delta PaCO2 increased to 3.44 ml.min-1.100 g-1. Torr-1 during anoxia. The increases in CBF occurred at constant mean arterial blood pressure, which indicates that cerebral vascular resistance decreased. The increased CBF response during asphyxia (hypercapnia-anoxia) could be beneficial for survival during prolonged dives by increasing glucose delivery for brain anaerobic metabolism. In addition, increased CBF could aid in regulating brain acid-base composition by controlling extracellular fluid PCO2.
New adipocyte formation in mice during refeeding after long-term deprivation
Authors: Ochi M. , Yoshioka H. , Sawada T. , Kusunoki T. , Hattori T.
Published: December 2017

Cell kinetic characteristics of the epididymal adipose tissue of mice were examined during refeeding after prolonged food deprivation. Mature mice were given a glucose-electrolyte solution for 20-40 days, and subsequent to a body weight loss of 35%, they were given normal mouse food ad libitum. After refeeding, their body weight and adipose tissue weight returned to the levels before the deprivation. We examined the formation of new adipocytes in the epididymal adipose tissue with [3H]thymidine autoradiography. Flash labeling experiments revealed that cell proliferation was most active on the 6th day after refeeding and decreased thereafter until the 13th day when few labeled cells were seen. Cumulative labeling experiments showed that replicated poorly differentiated mesenchymal cells developed into adipocytes by storing fat droplets. New adipocyte formation was observed in adult mice during refeeding after long-term deprivation.
Effect of atrial natriuretic peptide on thirst and arginine vasopressin release in humans
Authors: Burrell L. M. , Lambert H. J. , Baylis P. H.
Published: December 2017

We investigated the effect of human alpha-atrial natriuretic peptide (alpha-hANP) on osmotically stimulated arginine vasopressin (AVP) secretion and thirst appreciation. Seven normal male volunteers were studied on two occasions: synthetic alpha-hANP-(99-126) (2 pmol.kg-1.min-1) or control was infused intravenously for 30 min before and for the first 60 min of a 120-min hypertonic saline (855 mmol/l) infusion (0.06 ml.kg-1.min-1). Plasma ANP did not alter significantly during infusion of control and hypertonic saline (C+HS) but rose to steady-state concentrations of 17.4 +/- 3.2 pmol/l during infusion of ANP and hypertonic saline (ANP+HS). Plasma osmolality increased on both study days [ANP+HS: 284.4 +/- 0.6 to 299.7 +/- 1.1 mosmol/kgH2O (P less than 0.01)], C+HS: 283.6 +/- 1.2 to 299.1 +/- 1.6 mosmol/kgH2O (P less than 0.01)], as did plasma sodium [ANP+HS: 139.0 +/- 0.6 to 148.0 +/- 0.4 mmol/l (P less than 0.01), C+HS: 137.6 +/- 0.75 to 145.8 +/- 0.7 mmol/l (P less than 0.01)] and blood volume (ANP+HS: 7.7 +/- 0.6%, C+HS: 9.4 +/- 1.0%). The increase in plasma osmolality was accompanied by an increase in plasma AVP [ANP+HS: 1.4 +/- 0.3 to 8.3 +/- 1.2 pmol/l (P less than 0.01), C+HS: 1.6 +/- 0.4 to 7.8 +/- 1.5 pmol/l (P less than 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)
Augmentation of endotoxic lethality and glucose dyshomeostasis by phorbol ester
Authors: Inaba H. , Filkins J. P.
Published: December 2017

To investigate the role of protein kinase C (PKC) activation in the pathogenesis of endotoxin (ETX) shock, the in vivo effects of phorbol 12-myristate 13-acetate (PMA) on ETX-induced lethality and glucose dyshomeostasis were determined. Fed rats (300-400 g) were treated intravenously with incremental doses of Salmonella enteritidis ETX and either the vehicle, 110 mg/kg ip dimethyl sulfoxide (DMSO), or 0.5 mg/kg ip PMA dissolved in DMSO. PMA significantly increased ETX-induced lethality to doses of 1.0-20 mg/kg. PMA augmented the initial hyperglycemia, late hypoglycemia, and hyperlactacidemia after 1 mg/kg iv ETX to rats anesthetized with pentobarbital sodium. In contrast, 4 alpha-phorbol, a phorbol derivative that does not activate PKC, had no effect on either lethality or the glucose and lactate responses. Hyperinsulinemia after 1 mg/kg iv ETX was prolonged by PMA but not by 4 alpha-phorbol. Insulin tolerance testing (0.5 U/kg iv) produced an exaggerated hypoglycemic response in PMA-treated endotoxic (0.33 mg/kg) rats. Glucose tolerance to 1.2 g/kg iv was increased by ETX and PMA attenuated the increased tolerance. Thus PKC activation may be involved in the pathogenesis of lethal endotoxicosis and associated glucose dyshomeostasis.
Food deprivation-induced vs. drug-induced feeding: a behavioral evaluation
Authors: Levine A. S. , Kuskowski M. A. , Grace M. , Billington C. J.
Published: December 2017

Several neuroactive substances including neuropeptide Y (NPY), muscimol, and norepinephrine (NE) stimulate feeding in satiated rats. In the present study, we observed the behavioral patterns of rats stimulated to eat by food deprivation or by intracerebroventricular (icv) injection of orexigenic agents to explore the hypothesis that such agents produce a behavioral state resembling hunger. Animals that were food deprived for 24 h spent the majority of their time eating (35%), drinking (5%), resting (44%), and moving (13%) when food was available. If food was removed and substituted with a chewable substrate (plastic tube), they chewed on tubes for a brief period (5%) but spent most of their time moving (14%) or resting (77%). In the absence of food or tubes, they briefly moved about the cage (4%) and spent almost all of their time resting (94%). The patterns observed with the orexigenic drugs were different, particularly in the absence of food. NPY-injected rats were more active than deprived rats, spending 22% of their time moving in the presence of food, 47% in the presence of tubes, and 37% in the absence of food or tubes. Rats injected with muscimol demonstrated a marked increase in the time spent chewing and eating. These rats spent 67% of their time eating in the presence of food and chewed 25% of the time in the absence of either food or tubes. NE-injected rats also chewed when tubes were present (17%) or when no food or tubes were present (10%). Lag sequential analysis further documented differences in behavioral patterns amongst the various treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal glycyl-L-phenylalanine and L-phenylalanine transport in a euryhaline teleost
Authors: Reshkin S. J. , Ahearn G. A.
Published: December 2017

The transport mechanisms for the dipeptide glycyl-L-phenylalanine (Gly-Phe) and L-phenylalanine (Phe) were characterized in fish intestinal brush-border membrane vesicles (BBMV). Gly-Phe was rapidly hydrolyzed only intravesicularly with almost total hydrolysis occurring even at 10 s. Dipeptide uptake was not stimulated by an inward gradient of Na, K, or H. Phe uptake was stimulated by an inward gradient of either Na or K but displayed an overshoot phenomenon only in the presence of an Na gradient. Kinetic analysis of the effect of substrate concentration on transport rate revealed that transport of both Gly-Phe and Phe occurred by a saturable process conforming to Michaelis-Menten kinetics. The Km for Gly-Phe was 9.8 +/- 3.5 mM, whereas that for Phe in the presence of Na or K, respectively, was 0.74 +/- 0.13 and 1.1 +/- 0.37 mM. Maximum uptake for Gly-Phe and for Phe in the presence of Na and K was 5.1, 0.9, and 0.4 nmol.mg and protein-1.5 s-1, respectively. Gly-Phe and Phe transport displayed different patterns of inhibition by dipeptides and amino acids. These results suggest that Gly-Phe and Phe are transported via different mechanisms, with Gly-Phe being hydrolyzed during a carrier-mediated, cation-independent process and Phe being transferred via a Na+ cotransport process similar to that described in mammals. During conditions of high luminal dipeptide concentrations, the Gly-Phe pathway may make a significant contribution to total Phe uptake.
Water hydrogen incorporation into body fat in pigs: effect on double/triple-labeled water method
Authors: Haggarty P. , McGaw B. A. , Fuller M. F. , Christie S. L. , Wong W. W.
Published: December 2017

A basic assumption of the doubly labeled water (DLW) and triply labeled water (TLW) methods for measuring water flux (rH2O), CO2 production (rCO2), and fractionated water loss (X) is that the H of body water only leaves the body as water. Any loss of isotopes in other products will introduce an error into these techniques. The body fat represents the largest potential sink for water H. 2H sequestration into the carcass fatty acids was investigated in eight pigs labeled with 2H2O for 21 days. rCO2 was measured simultaneously in respiration chambers to allow an accurate assessment of the effect of 2H sequestration on the estimated rCO2. The fat content of the diet (1.63%), level of intake, and stage of maturity were all designed to give the widest possible range of sequestration effects. Four animals were restricted to their estimated maintenance requirement and four were allowed to feed ad libitum giving a range of weight gain from 100 to 650 g/day. This was reflected in the estimated error on rH2O (+0.42% in the restricted group and +2.52% in the fast-growing animals) and on rCO2 (-1.30 and -7.59%, respectively). The error on the calculation of X using TLW was +0.03 units in the restricted group and +0.20 units in the fast-growing animals. The error of +0.2 on X propagates through to an underestimate of rCO2 of approximately 4%, and since this is additive with the error on DLW the ultimate error on rCO2 using TLW would be approximately -12%.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal response to 7 days of lower body positive pressure in squirrel monkeys
Authors: Churchill S. E. , Pollock D. M. , Natale M. E. , Moore-Ede M. C.
Published: December 2017

The purpose of this study was to characterize the renal response to central volume expansion using lower body positive pressure (LBPP) in the adult male squirrel monkey (Saimiri sciureus). Urinary excretion of sodium, potassium, and water and plasma aldosterone concentrations were measured during a control day, 7 days of LBPP, and a recovery day. Time control experiments in the same animals included chair sitting without exposure to LBPP. Seven monkeys (600-1,000 g) were trained to sit in a specially designed metabolism chair before chronic implantation of arterial and venous catheters to facilitate maintenance infusion of saline, monitoring of vascular pressures, and blood sampling; urine was collected via a condomlike tube. A cephalad shift in body fluid was induced by applying 20 mmHg of air pressure from the waist down. Urine volume and sodium excretion were increased significantly (28 to 52 ml/day and 0.4 to 3.5 meq/day, respectively) during the initial 24 h of LBPP with most of this response occurring in the first 6-12 h. From the 2nd to the 7th day of LBPP, urinary excretion rates for sodium and water were not different from chair-sitting controls. Water and sodium balance significantly decreased from +15 to -12 ml/day and from +1.1 to -2.2 meq/day, respectively, from the control to the first day of LBPP. This change in balance was not observed in the time-control group. Removal of the stimulus resulted in a modest conservation of sodium and water. The renal responses were not associated with any changes in plasma aldosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Characteristics of renal transport of taurine in reptilian brush-border membranes
Authors: Benyajati S. , Johnson J. L.
Published: December 2017

We examined characteristics of taurine transport across renal brush-border membranes (BBM) of the garter snake (Thamnophis sirtalis), a species that demonstrates both net reabsorption and secretion of taurine in vivo. Transport was examined by a rapid filtration technique at 25 degrees C. Inwardly directed Na+ gradient specifically stimulated taurine uptake. Under initial taurine equilibrium condition, a small overshoot of taurine uptake driven by an inwardly directed NaCl gradient could be observed. No stimulation of taurine uptake was observed under Na+ equilibrium or K+, Li+, or choline gradients conditions. Reptilian renal BBM taurine transport also displayed specific Cl- requirement: replacement of NaCl by NaSCN or Na(+)-gluconate gradients inhibited taurine uptake. The uptake was stimulated under Cl- gradient compared with Cl- equilibrium conditions. Taurine transport was not stimulated by H+ gradient in either direction, although it was inhibited by acidic pH (less than 7.0). Amiloride and furosemide had no effects. The transport was electrogenic, stimulated by an inside negative membrane potential, and inhibited by other beta-amino acids. Overall, the reptilian BBM transport system for taurine resembles those observed in both mammalian and fish renal BBM.
High potassium intake attenuates antinatriuretic response to air stress in DOCA-salt rats
Authors: Sato Y. , Ando K. , Ogata E. , Fujita T.
Published: December 2017

We studied the effects of potassium supplementation (2 wk of 0.5% KCl to drink) on responses of renal function to a stressful environmental stimulus (air stress) in deoxycorticosterone acetate (DOCA)-salt rats. In conscious DOCA-salt rats, air stress decreased urine flow rate and urinary sodium excretion without changes in effective renal plasma flow and glomerular filtration rate, whereas in normotensive vehicle-treated rats air stress had no effect on these measures. Renal denervation abolished the antidiuretic and antinatriuretic responses to air stress in DOCA-salt rats. Correspondingly potassium supplementation in DOCA-salt rats could not only reduce basal blood pressure significantly but also attenuate the antidiuretic and antinatriuretic responses to air stress without renal denervation. Evidence suggests that the attenuation by potassium supplementation of air stress-induced decrease in urine flow and sodium excretion in DOCA-salt rats may be partly involved in the natriuretic and the resultant antihypertensive actions of potassium in DOCA-salt hypertensive rats, but the mechanisms could not be clarified by the present study.
Arginine vasopressin responses to hypoxia and hypercapnia in late-gestation fetal sheep
Authors: Raff H. , Kane C. W. , Wood C. E.
Published: December 2017

The purpose of this study was to determine the interaction of hypoxia and hypercapnia in the control of arginine vasopressin (AVP) secretion in fetal sheep and to determine the role of the peripheral arterial chemoreceptors in that response. We measured the plasma AVP response to hypercapnia and/or hypoxia in catheterized intact or sinoaortic-denervated fetal sheep between 123 and 144 days of gestation. Ewes were exposed to the following inspired gases: two successive 30-min periods of normocapnic normoxia, 30 min of normocapnic normoxia followed by 30 min of normocapnic hypoxia, two successive 30-min periods of hypercapnic normoxia, or 30 min of hypercapnic normoxia followed by 30 min of hypercapnic hypoxia (i.e., asphyxia). Hypercapnia per se had no significant effect on fetal plasma AVP. Normocapnic hypoxia per se resulted in a significant increase in fetal plasma AVP. Although hypercapnia resulted in a significant acidemia, the decrease in arterial pH was more marked under hypoxic conditions. Hypercapnia/acidemia augmented the AVP response to hypoxia. Fetal sinoaortic denervation did not significantly attenuate any of the AVP responses. We conclude that hypercapnia augments the fetal AVP response to hypoxia and that the AVP response to neither normocapnic nor hypercapnic hypoxia is dependent on afferent information carried in the carotid sinus or aortic nerves.
Effect of water restriction during growth and adulthood on kidney morphology of bobwhite quail
Authors: Goldstein D. L. , Ellis C. C.
Published: December 2017

We raised bobwhite quail (Colinus virginianus) either with unrestricted water (HYD birds) or with restricted water (DEH birds). DEH quail grew more slowly and reached lower adult body mass. Despite this, kidney mass was not different in the two groups. The number of nephrons per kidney, heterogeneity of glomerular sizes, number of medullary cones per kidney, and lengths of medullary cones (equivalent to the lengths of the longest loops of Henle) did not differ between HYD and DEH quail. However, the mass of an individual medullary cone was greater in the DEH birds; this included both hypertrophy and hyperplasia of the epithelia in thick ascending limbs of Henle and hypertrophy without hyperplasia in the collecting ducts. We found no differences among groups in the sizes of tubule cross sections from cortical nephron segments (proximal tubules). Water restriction of HYD birds for 5 days as adults stimulated tubule hypertrophy but not to the same extent as the chronic regimen and with no evidence for hyperplasia. DEH quail given unrestricted water as adults maintained elevated drinking rates for the full week water was available; this rehydration had no effect on sizes of tubule epithelia.
Meal-related and rhythmic drinking: effects of abolition of rat's eating rhythm
Authors: Johnson R. F. , Johnson A. K.
Published: December 2017

Eating and drinking in the rat, which are both highly rhythmic and nocturnal activities, are temporally and quantitatively associated. The present study abolished the rhythmicity of eating by temporally and quantitatively restricting food access to 12 equally sized bihourly meals daily (total food available was equal to 80% of daily ad libitum intake). Water access remained ad libitum and was monitored and quantified in terms of 1) nocturnality, 2) association with meals, and 3) changes in the association of food and water intake across the phases of the light-dark cycle. Similar parameters were obtained from the same rats with ad libitum access to both food and water. The results indicate that both rhythmic and meal-induced effects are detectable in the drinking of rats with restricted food access, although both the rhythmic and meal-associated factors are reduced compared with drinking under ad libitum food access. Most important, the data clearly demonstrate large changes in the association of food and water intake across the phases of the light-dark cycle. These findings indicate a complex interaction of meal-associated and rhythmic factors in the control of drinking.
Tissue- and species-specific differences in ligand binding to thromboxane A2 receptors
Authors: Dorn G. W.
Published: December 2017

The ligand binding site of vascular smooth muscle (VSM) and platelet thromboxane A2 (TxA2) receptors was characterized in humans and rabbits using the TxA2 mimetic [125I]BOP. Vessel contraction and platelet aggregation studies demonstrated that unlabeled I-BOP and the prostaglandin H2 (PGH2) mimetic U-46619 were potent agonists in rabbit aortas, human saphenous veins, and washed human and rabbit platelets. [125I]BOP bound saturably to a single site on cultured vascular smooth muscle (VSM) cells from rabbit aortas and human saphenous veins with dissociation constants (Kd) of 392 +/- 8 (n = 5) and 390 +/- 120 pM (n = 6) and binding capacities (Bmax) of 5,322 +/- 200 and 2,017 +/- 322 sites/cell, respectively. [125I]BOP also bound saturably to one site on rabbit platelets (Kd = 415 +/- 15 pM, Bmax = 594 +/- 43 sites/platelet, n = 4) but, in agreement with previous studies, to two sites on human platelets (high-affinity Kd = 118 +/- 24 pM, Bmax = 121 +/- 33 sites/platelet; low-affinity Kd = 1.1 +/- 0.47 nM, Bmax 232 +/- 23 sites/platelet, n = 4). [125I]BOP was displaced from its binding site on rabbit and human VSM and platelets by stable TxA2/PGH2 analogues possessing either agonist or antagonist activity but not by other prostaglandins. The rank orders of the binding inhibition constants (IC50) for the TxA2/PGH2 analogues were compared among the four tissues and were highly correlated (r = 0.963) in VSM and platelets from rabbits but not humans (r = 0.699), suggesting that human VSM TxA2 receptors may be distinct from platelet TxA2 receptors. The IC50 rank order was also highly correlated (r = 0.935) between human and rabbit platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ovariectomy on vasopressin, ACTH, and renin activity responses to hypotension
Authors: Keller-Wood M. , Wood C. E.
Published: December 2017

The gonadal axis is thought to modulate adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), and plasma renin activity (PRA) responses to stimuli in several species. These experiments were designed to compare the responses to hypotension in chronically ovariectomized ewes and intact ewes. The ewes were infused with nitroprusside at rates of 5, 10, or 15 micrograms.kg-1.min-1 or infused with vehicle for 10 min. The response to 15 micrograms.kg-1.min-1 was also tested with or without treatment with 10 mg of dexamethasone 2 h before nitroprusside. Blood samples were collected before and at 5, 10, 15, 20, and 30 min after the start of the infusion for measurement of plasma ACTH, AVP, and PRA. In both groups of animals there were significant responses to hypotension. There was a significant effect of ovariectomy on ACTH, AVP, and PRA responses. ACTH and PRA responses were lower in the ovariectomized ewes; AVP responses were increased in the ovariectomized ewes. Administration of dexamethasone inhibited ACTH responses and did not inhibit PRA responses in both groups of ewes. Administration of dexamethasone did not inhibit the AVP response in the intact ewes but did reduce the response in the ovariectomized ewes.
High dietary sodium enhances gustatory nerve activity and behavioral responses to NaCl
Authors: Priehs T. W. , Mooney K. J. , Bernard R. A.
Published: December 2017

Neural and behavioral taste responses to NaCl were studied in rats receiving a high-salt diet. Salt preferences and voluntary sodium intake were measured by the 24-h two-bottle choice method over a wide concentration range of NaCl solutions. As expected, the salt-loaded rats showed lower preference responses for all the solutions tested, which were presented in ascending order from 0.001 to 1.0 M NaCl. However, they freely ingested significantly greater amounts of sodium than the controls by drinking larger volumes of saline solution throughout the hypotonic concentration range, from 0.001 to 0.1 M NaCl. They showed lower voluntary intake of sodium only for isotonic and hypertonic solutions. Electrophysiological recordings from the chorda tympani nerve showed that the taste responses of the salt-loaded rats were greater in magnitude than those of the controls, and the neural stimulus-response function of the experimental group had a significantly steeper slope but no apparent difference in threshold. These experiments indicate that salt-loaded rats have enhanced appetitive responses to NaCl that may be mediated by increased sensory input.
Tetrahydrofolic acid as the principal congener of plasma folates in pigs
Authors: Natsuhori M. , Shimoda M. , Kokue E. , Hayama T. , Takahashi Y.
Published: December 2017

Concentrations of pig plasma folates were determined by a high-performance liquid chromatography with an electrochemical detector (HPLC-ECD). Tetrahydrofolic acid (THF) and 5-methyltetrahydrofolic acid (5-MF) were found to be the plasma folates. The concentration of THF (10.3 +/- 4.3 ng/ml) was significantly higher than that of 5-MF (3.5 +/- 1.0 ng/ml). The sum of the THF and 5-MF concentrations determined by the HPLC-ECD analysis in Gottingen miniature pigs was comparable to the total folate concentration of the same plasma sample determined by a radioligand assay. No or only trace amounts of THF were found in the plasma of the rats, mice, rabbits, dogs, cows, horses, or humans. Although 5-MF is generally recognized as the only principal plasma folate in many species, THF may be the principal congener with 5-MF as a secondary congener in the pig.
Morphine-induced stimulation of fetal breathing: role of mu 1-receptors and central muscarinic pathways
Authors: Szeto H. H. , Cheng P. Y. , Dwyer G. , Decena J. A. , Wu D. L. , Cheng Y.
Published: December 2017

The mechanism of action of low doses of morphine on breathing dynamics in the fetus was studied in 16 fetal lambs with chronically implanted electromyographic electrodes in the diaphragm. Morphine (0.15-2.5 mg/h) caused a significant dose-dependent increase in the number of diaphragmatic bursts per hour, with either an increase or no change in instantaneous breathing rate. There was also a significant dose-related increase in the continuity of the breathing pattern, as indicated by a decrease in the number of apneas per hour, and an increase in epoch duration. Morphine also had a significant effect on the stability of the breathing pattern, with an increase in the percentage of bursts that occurred in stable clusters. All of these effects were completely abolished by concurrent intracerebroventricular administration of either methylnaloxone or methylatropine or by pretreatment with intravenous naloxonazine. These results suggest that stimulation and stabilization of ventilatory activity in the fetal lamb by low doses of morphine are mediated via mu 1-receptors and involve central muscarinic pathways.
Regional blood-brain barrier transport of cationized bovine serum albumin in awake rats
Authors: Shimon-Hophy M. , Wadhwani K. C. , Chandrasekaran K. , Larson D. , Smith Q. R. , Rapoport S. I.
Published: December 2017

Regional blood-brain barrier permeability-surface area products (PAs) of cationized bovine serum albumin (cBSA) with isoelectric point (pI) approximately 8 or greater than or equal to 11 and of native bovine serum albumin (nBSA;pI approximately 4) were determined in awake male Sprague-Dawley rats after bolus intravenous injection. The albumins were labeled with 125I. Brain uptakes were assessed by autoradiography and by direct assay of radioactivity in brain regions. nBSA uptake into brain was statistically insignificant over 3 h, whereas cBSA uptake was significantly even at 6 min. Mean PA values of cBSA with pI approximately 11 (1.69-2.65 x 10(-5) ml.s-1.g-1) in most brain regions were twofold higher than PAs of cBSA with pI approximately 8 (0.98-1.37 x 10(-5) ml.s-1.g-1), whereas mean PA for nBSA did not differ significantly from zero. Autoradiographs of brain slices and net distributions in brain compartments at 6 and 30 min after injection suggested that cBSA entered the brain parenchyma via blood vessels and cerebrospinal fluid but that the former was the main route. The results quantitate for the first time regional brain PA values for cationized proteins and suggest specific mechanisms at cerebral blood vessels that distinguish transport of cationized from noncationized macromolecules.
Role of intrarenal angiotensin II in mediating renal response to volume expansion
Authors: Pinilla J. M. , Perez M. C. , Hernandez I. , Quesada T. , Garcia-Estan J. , Salazar F. J.
Published: December 2017

Natriuresis induced by extracellular volume expansion (ECVE) is accompanied by a decrease in renin release and by an increase of renal interstitial hydrostatic pressure (RIHP). This study was undertaken to examine, in anesthetized dogs, the relative role of intrarenal angiotensin II (ANG II) changes in mediating natriuresis, diuresis, and increases in RIHP induced by two different levels of volume expansion (1.5 and 5% body wt in 45 min) with isotonic saline. Intrarenal ANG II levels were maintained in the right kidney throughout the experiment by simultaneously infusing captopril (0.8 micrograms.kg-1.min-1) and ANG II (1 ng.kg-1.min-1) into the right renal artery. In response to 5% ECVE, increases in RIHP, natriuresis, and diuresis were inhibited in the right kidney by 55, 40, and 47% respectively, when compared with the left kidney. Significant increases occurred in plasma atrial natriuretic peptide (ANP) levels during 5% ECVE. Maintenance of constant intrarenal ANG II levels during 1.5% ECVE completely abolished the increment of RIHP and diuresis and inhibited the natriuretic response by 80% in the right kidney when compared with the left kidney. Plasma ANP levels did not change during the 1.5% ECVE. No differences between kidneys were found when the intrarenal effects of ANG II were blocked with saralasin before saline loading. These results suggest that increases in RIHP, natriuresis, and diuresis during ECVE are partially mediated by decreases in intrarenal ANG II levels. Furthermore, these results indicate that the role of intrarenal ANG II levels in mediating the renal response to ECVE is more important when plasma ANP levels do not change than when they are increased.
Differential feeding responses to bacterial lipopolysaccharide and muramyl dipeptide
Authors: Langhans W. , Balkowski G. , Savoldelli D.
Published: December 2017

The present study was designed to test whether a tolerance to the hypophagic effects of bacterial lipopolysaccharide (LPS) and muramyl dipeptide (MDP) develops with repeated injections in rats and whether a relationship between the hypophagic effects of both compounds exists. Only the first of three subsequent intraperitoneal injection of LPS (100 micrograms/kg body wt each), given every 2nd day, led to a significant reduction of food intake. In contrast, MDP (1.6 mg/kg body wt) did not lose its hypophagic effect with four subsequent intraperitoneal injections. Furthermore, the LPS tolerance did not alter the hypophagic response to subsequently injected MDP. Likewise, MDP pretreatment did not alter the hypophagic response to LPS. Doses of MDP and LPS that were individually below the threshold for a reliable reduction of food intake (0.4 mg MDP/kg body wt + 25 micrograms LPS/kg body wt) reduced food intake synergistically when injected together. The hypophagia produced by combined injections of MDP plus LPS slowly diminished with repeated injections. The results indicate that separate but interacting mechanisms are involved in the feeding responses to MDP and LPS. The observed synergism between MDP and LPS suggests a synergistic role of bacterial muramyl peptides and LPS in the anorexia during bacterial infections.
Circadian characteristics of Djungarian hamsters: effects of photoperiodic pretreatment and artificial selection
Authors: Puchalski W. , Lynch G. R.
Published: December 2017

Bidirectional artificial selection for (High Line) and against (Low Line) photoresponsiveness altered the percent of photoresponsive hamsters within lines and affected circadian function of hamsters identical in photoresponsiveness. For example, free-running period was shorter in responsive relative to nonresponsive hamsters. Between-line differences for responders and nonresponders were also found: hamsters from the High Line had a shorter free-running period relative to Low Line hamsters. However, phase angle of entrainment to long and short days was not affected. In general, expression of circadian rhythmicity was extraordinarily inflexible in photononresponsive hamsters from both lines: 1) phase angle of entrainment to lights on was similar under short and long day; 2) activity duration was similar under long and short days, although some decompression occurred in constant dark; 3) aftereffects on the free-running period were absent; and 4) amplitude of the phase-response curve was small (+/- 1 h) and present only at circadian times 10-24. We propose that selection for or against photoresponsiveness may have affected the interaction of component oscillators underlying circadian rhythmicity.
The adenosine receptor blocker aminophylline increases anoxic ethanol excretion in crucian carp
Authors: Nilsson G. E.
Published: December 2017

By depressing energy consumption, anoxia-tolerant animals are thought to compensate for a reduced ability to produce energy during anoxia. Adenosine is an inhibitory neuromodulator in vertebrates and, hence, has the potential ability to depress energy consumption. Ethanol is the main metabolic end product in anoxic Carassius, and the present study shows that the rate of ethanol excretion in anoxic crucian carp (Carassius carassius L.) can be increased threefold by treatment with the adenosine receptor antagonist aminophylline (75 mg/kg). By contrast, the same dose of aminophylline did not increase the rate of routine oxygen consumption during normoxia. It is hypothesized that adenosine acts as a metabolic depressant during anoxia in crucian carp.
Influence of splenectomy on hemodynamics during cardiac tamponade
Authors: Hoit B. D. , Gabel M. , Fowler N. O.
Published: December 2017

The effect of prior splenectomy on the hemodynamics of cardiac tamponade was investigated in 15 closed-chest pentobarbital sodium-anesthetized dogs. Hemodynamics were compared at baseline and during staged cardiac tamponade (pericardial pressures of 5, 10, and 15 mmHg) at control (n = 15) and after splenectomy (n = 8) and sham operation (n = 7). The fall in mean arterial pressure with cardiac tamponade was significantly greater in splenectomized dogs than in either sham-operated or control dogs (P less than 0.001). Cardiac output was more depressed at the third level of cardiac tamponade in splenectomized than in sham-operated or control dogs (12.8 +/- 14.5 vs. 29.3 +/- 8.7 and 25.4 +/- 9.4 ml.min-1.kg-1, respectively; both P less than 0.05 vs. splenectomy). Hemodynamic failure, defined as an inability to maintain mean arterial pressure greater than 50 mmHg for 5 min, occurred at a lower pericardial pressure in splenectomized than in sham-operated dogs (13.1 +/- 3.8 vs. 18.1 +/- 3.5 mmHg, P less than 0.05). Hematocrit increased significantly with cardiac tamponade in controls and sham-operated but not splenectomized dogs. The percent increase in hematocrit from baseline to the third stage of cardiac tamponade was 19.6 +/- 9.8 and 22.3 +/- 5.6% in control and sham dogs, respectively. Thus the canine spleen plays an important role in cardiovascular compensation to cardiac tamponade. Parallel changes in hematocrit suggest that a part of this response is due to splenic autotransfusion.
Regularly scheduled voluntary exercise synchronizes the mouse circadian clock
Authors: Edgar D. M. , Dement W. C.
Published: December 2017

Circadian rhythm entrainment has long been thought to depend exclusively on periodic cues in the external environment. However, evidence now suggests that appropriately timed vigorous activity may also phase shift the circadian clock. Previously it was not known whether levels of exercise/activity associated with spontaneous behavior provided sufficient feedback to phase shift or synchronize circadian rhythms. The present study investigated this issue by monitoring the sleep-wake, drinking, and wheel-running circadian rhythms of mice (Mus musculus) during unrestricted access to running wheels and when free wheel rotation was limited to either 12- or 6-h intervals with a fixed period of 24 h. Wheel rotation was controlled remotely. Mice spontaneously ran in wheels during scheduled access, and free-running sleep-wake and drinking circadian rhythms became entrained to scheduled exercise in 11 of 15 animals. However, steady-state entrainment was achieved only when exercise commenced several hours into the subjective night. The temporal placement of running during entrainment was related (r = 0.7003, P less than 0.02) to free-running period before entrainment. Mice with a free-running period less than 23.0 h did not entrain but exhibited relative coordination between free-running variables and the wheel availability schedule. Thus the circadian timekeeping system responds to temporal feedback arising from the timing of volitional exercise/activity, suggesting that the biological clock not only is responsive to periodic geophysical events in the external environment but also derives physiological feedback from the spontaneous activity behaviors of the organism.
Ultradian variations of chromogranin A in humans
Authors: Takiyyuddin M. A. , Neumann H. P. , Cervenka J. H. , Kennedy B. , Dinh T. Q. , Ziegler M. G. , Baron A. D. , O'Connor D. T.
Published: December 2017

Chromogranin A (CgA) is an acidic soluble protein exocytotically released from virtually all neuroendocrine secretory vesicles. Here we examined spontaneous variations in CgA and catecholamine concentrations in humans. In normal subjects, basal CgA showed no day-to-day, week-to-week, or diurnal variability. Plasma CgA had significant ultradian variation in normotensives and hypertensives, and in bilaterally adrenalectomized subjects. Gender, but not age or blood pressure, influenced CgA variations, males having fewer (P less than 0.05) peaks per 8 h. Plasma catecholamines had significant ultradian variations in both controls and bilaterally adrenalectomized subjects. Within individuals, neither basal nor peak plasma CgA correlated with catecholamines, nor was there concordance between plasma CgA and catecholamine peaks. Somatostatin, a widespread inhibitor of nonsympathoadrenal neuroendocrine secretion, diminished both the frequency and amplitude of plasma CgA peaks. Thus spontaneous variations in basal CgA are not directly linked to alterations in sympathoadrenal catecholamine secretion. Furthermore, neuroendocrine secretion at sites other than the sympathoadrenal system contributes to spontaneous variations in CgA concentration.
The interactive effects of dietary sodium chloride and calcium on cardiovascular stress responses
Authors: Scrogin K. E. , Hatton D. C. , McCarron D. A.
Published: December 2017

Blood pressure increases associated with salt loading in the spontaneously hypertensive rat (SHR) are attenuated with increased dietary calcium. To assess the cardiovascular effects of these nutrients during stress, blood pressure and sympathoadrenal responses to stress were compared in salt-sensitive SHRs fed diets containing normal (0.73%) or high (8.0%) NaCl combined with either low (0.2%) or high (2.0%) calcium. NaCl-loaded rats showed increased blood pressure and exaggerated plasma epinephrine changes during restraint stress. Elevated blood pressure responses to exogenous NE were also observed with high salt intake. Supplementary calcium reduced blood pressure and attenuated the hypertensive effect of NaCl during restraint stress. Animals fed the high calcium diets had lower plasma epinephrine levels while vascular reactivity was not affected. The results indicate that increased sympathoadrenal activity and vascular reactivity contribute to elevated blood pressure and exaggerated pressor responses produced by NaCl loading in the salt-sensitive SHR. However, the hypotensive effects of dietary calcium appear to be related to sympathoadrenal activity but not vascular reactivity.
Antihypertensive effect of dietary calcium loading in angiotensin II-salt rats
Authors: Ando K. , Sato Y. , Ono A. , Takahashi K. , Shimosawa T. , Ogata E. , Fujita T.
Published: December 2017

To clarify the hypotensive effect of high dietary Ca intake on salt-sensitive hypertension, 7-wk-old Sprague-Dawley rats, 3.15% Na and/or 4.07% Ca diet loaded, were administered 125 ng/ml of angiotensin II (ANG II) intraperitoneally for 12 days. Compared with control rats (mean blood pressure 108 +/- 2 mmHg), ANG II administration caused hypertension (131 +/- 4 mmHg, P less than 0.05). Na loading enhanced the hypertensive effect of ANG II (161 +/- 4 mmHg, P less than 0.01). Dietary Ca loading did not significantly inhibit the pressor effect of ANG II alone (119 +/- 4 mmHg). However, Ca loading suppressed hypertension in ANG II-salt rats (126 +/- 4 mmHg, P less than 0.01). Plasma total catecholamine (norepinephrine + epinephrine) was increased in ANG II-salt rats (176 +/- 14 vs. 290 +/- 23 pg/ml, P less than 0.05), but Ca loading decreased plasma catecholamine (182 +/- 13 pg/ml, P less than 0.05). In contrast, plasma catecholamine was not significantly different between ANG II-treated rats with and without Ca loading. Ca loading increased serum Ca in ANG II rats (10.9 +/- 0.1 vs. 11.7 +/- 0.1 mg/dl, P less than 0.05) but did not do so significantly in ANG II-salt rats (10.8 +/- 0.2 vs. 10.9 +/- 0.1 mg/dl). Thus Ca loading exclusively ameliorated salt-sensitive hypertension, which was induced with ANG II administration and Na loading in rats, probably through suppression of the increased sympathetic activity. In addition, these effects of Ca loading were not mediated through an increased blood level of Ca.
Measurement of D-xylose gut absorptive capacity in conscious rats
Authors: Singh G. , Chaudry K. I. , Chudler L. C. , O'Neill P. J. , Chaudry I. H.
Published: December 2017

Recently, it has become evident that the gut plays a central role in the development of multiple organ failure in the critically ill patient after trauma-hemorrhage and sepsis. However, it remains unknown whether gut absorptive capacity (GAC) is altered under those conditions. The aim of this study, therefore, was to use a rat model for GAC measurements independent of the function of other organs and to determine whether GAC is altered after trauma. Rats (n = 79; 250-325 g) were lightly anesthetized with ether, and a 6-cm midline laparotomy was performed (i.e., trauma induced). A nasogastric tube was inserted and after cannulation of various blood vessels, the animals were allowed to recover from anesthesia. They were then divided into various groups for determinations of GAC over a period of 5 days. Control animals had GAC measurements without any surgery being performed on them. GAC was determined using the 1-h D-xylose absorption test and measuring D-xylose concentration in the portal blood. Results demonstrate that GAC 1) is significantly depressed for the first 48 h after trauma, 2) returns to normal 72 h after trauma, and 3) is further depressed by hemorrhage and resuscitation and by sepsis after trauma. Thus the model described here can be used to investigate the effects of trauma, trauma plus hemorrhage, trauma plus sepsis, hemorrhage alone, and sepsis alone on GAC, independent of the function of other organs.
Oxidative cost of breathing in the turtle Chrysemys picta bellii
Authors: Jackson D. C. , Singer J. H. , Downey P. T.
Published: December 2017

We estimated the cost of breathing of turtles by measuring ventilation and oxygen consumption during air breathing and CO2 breathing. We assumed that any increment in oxygen consumption due to hypercapnic hyperpnea was due to the metabolic cost of the increased breathing. Six turtles were studied while breathing air and then 5% CO2 in air after at least 12 h breathing each gas. For the measurements, the turtles were submerged unrestrained in water at 20 degrees C and were free to raise their heads into a ventilated chamber. Tidal volumes were measured by the pressure changes in the chamber, and oxygen consumption was measured by conventional open-circuit respirometry. Ventilation increased markedly during CO2 breathing up to 50 times the control level, but oxygen consumption increased only slightly. Assuming no depression in nonventilatory metabolism, our data indicate an oxidative cost of breathing on the order of 1% of the total metabolic rate at rest. This is far less than the 15-20% cost predicted from published work (Kinney et al., Respir. Physiol. 31: 327-332, 1976) on a closely related species of turtle and is consistent with earlier work in our laboratory. We conclude that the cost of breathing in turtles is low, similar to other air-breathing vertebrates, and therefore the existing notion that turtle breathing is expensive and inefficient should be discarded.