bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics, one-year change in ejection fraction and long-term outcomes in patients with heart failure with mid-range ejection fraction: a multicentre prospective observational study in Catalonia (Spain)
Authors: Farré Nuria , Lupon Josep , Roig Eulàlia , Gonzalez-Costello Jose , Vila Joan , Perez Silvia , de Antonio Marta , Solé-González Eduard , Sánchez-Enrique Cristina , Moliner Pedro , Ruiz Sonia , Enjuanes C , Mirabet Sonia , Bayés-Genís Antoni , Comin-Colet Josep
Published: December 2017

Objectives

The aim of this study was to analyse baseline characteristics and outcome of patients with heart failure and mid-range left ventricular ejection fraction (HFmrEF, left ventricular ejection fraction (LVEF) 40%–49%) and the effect of 1-year change in LVEF in this group.

Setting

Multicentre prospective observational study of ambulatory patients with HF followed up at four university hospitals with dedicated HF units.

Participants

Fourteen per cent (n=504) of the 3580 patients included had HFmrEF.

Interventions

Baseline characteristics, 1-year LVEF and outcomes were collected. All-cause death, HF hospitalisation and the composite end-point were the primary outcomes.

Results

Median follow-up was 3.66 (1.69–6.04) years. All-cause death, HF hospitalisation and the composite end-point were 47%, 35% and 59%, respectively. Outcomes were worse in HF with preserved ejection fraction (HFpEF) (LVEF>50%), without differences between HF with reduced ejection fraction (HFrEF) (LVEF<40%) and HFmrEF (all-cause mortality 52.6% vs 45.8% and 43.8%, respectively, P=0.001). After multivariable Cox regression analyses, no differences in all-cause death and the composite end-point were seen between the three groups. HF hospitalisation and cardiovascular death were not statistically different between patients with HFmrEF and HFrEF. At 1-year follow-up, 62% of patients with HFmrEF had LVEF measured: 24% had LVEF<40%, 43% maintained LVEF 40%–49% and 33% had LVEF>50%. While change in LVEF as continuous variable was not associated with better outcomes, those patients who evolved from HFmrEF to HFpEF did have a better outcome. Those who remained in the HFmrEF and HFrEF groups had higher all-cause mortality after adjustment for age, sex and baseline LVEF (HR 1.96 (95% CI 1.08 to 3.54, P=0.027) and HR 2.01 (95% CI 1.04 to 3.86, P=0.037), respectively).

Conclusions

Patients with HFmrEF have a clinical profile in-between HFpEF and HFrEF, without differences in all-cause mortality and the composite end-point between the three groups. At 1 year, patients with HFmrEF exhibited the greatest variability in LVEF and this change was associated with survival.
Remodeling of root morphology by CuO and ZnO nanoparticles: effects on drought tolerance for plants colonized by a beneficial pseudomonad
Authors: Yang Kwang-Yeol , Doxey Stephanie , McLean Joan E. , Britt David , Watson Andre , Al Qassy Dema , Jacobson Astrid , Anderson Anne J.
Published: December 2017

Formulations that include nanoparticles of CuO and ZnO are being considered for agricultural applications as fertilizers because they act as sources of Cu or Zn. Currently, few studies of the effects of these nanoparticles (NPs) consider the three-way interactions of NPs with the plant plus its microbiome. At doses that produced root shortening by both nanoparticles (NPs), CuO NPs induced the proliferation of elongated root hairs close to the root tip, and ZnO NPs increased lateral root formation in wheat seedlings (Triticum aestivum L.). These responses occurred with roots colonized by a beneficial bacterium, Pseudomonas chlororaphis O6 (PcO6), originally isolated from roots of wheat grown under dryland farming in calcareous soils. The PcO6-induced tolerance to drought stress in wheat seedlings was not impaired by the NPs. Rather, growth of the PcO6-colonized plants with NPs resulted in systemic increases in the expression of genes associated with tolerance to water stress. Increased expression in the shoots of other genes related to metal stress was consistent with higher levels of Cu and Zn in PcO6-colonized shoots grown with the NPs. This work demonstrates that plants grown with CuO or ZnO NPs showed cross-protection from different challenges such as metal stress and drought.
Impartial Selection and the Power of Up to Two Choices
Authors: Bjelde Antje , Fischer Felix , Klimm Max
Published: December 2017

We study mechanisms that select members of a set of agents based on nominations by other members and that are impartial in the sense that agents cannot influence their own chance of selection. Prior work has shown that deterministic mechanisms for selecting any fixed number
k
of agents are severely limited and cannot extract a constant fraction of the nominations of the
k
most highly nominated agents. We prove here that this impossibility result can be circumvented by allowing the mechanism to sometimes but not always select fewer than
k
agents. This added flexibility also improves the performance of randomized mechanisms, for which we show a separation between mechanisms that make exactly two or up to two choices and give upper and lower bounds for mechanisms allowed more than two choices.
Sequential Posted-Price Mechanisms with Correlated Valuations
Authors: Adamczyk Marek , Borodin Allan , Ferraioli Diodato , Keijzer Bart De , Leonardi Stefano
Published: December 2017

We study the revenue performance of sequential posted-price mechanisms and some natural extensions for a setting where the valuations of the buyers are drawn from a correlated distribution. Sequential posted-price mechanisms are conceptually simple mechanisms that work by proposing a “take-it-or-leave-it” offer to each buyer. We apply sequential posted-price mechanisms to single-parameter multiunit settings in which each buyer demands only one item and the mechanism can assign the service to at most
k
of the buyers.

For standard sequential posted-price mechanisms, we prove that with the valuation distribution having finite support, no sequential posted-price mechanism can extract a constant fraction of the optimal expected revenue, even with unlimited supply. We extend this result to the case of a continuous valuation distribution when various standard assumptions hold simultaneously (i.e., everywhere-supported, continuous, symmetric, and normalized (conditional) distributions that satisfy
regularity
, the
MHR condition
, and
affiliation
). In fact, it turns out that the best fraction of the optimal revenue that is extractable by a sequential posted-price mechanism is proportional to the ratio of the highest and lowest possible valuation.

We prove that a simple generalization of these mechanisms achieves a better revenue performance; namely, if the sequential posted-price mechanism has for each buyer the option of
either
proposing an offer
or
asking the buyer for its valuation, then a Ω (1/max { 1,
d
}) fraction of the optimal revenue can be extracted, where
d
denotes the degree of dependence of the valuations, ranging from complete independence (
d
=0) to arbitrary dependence (
d
=
n
-1).
Efficient Reconfigurable Architecture for Pricing Exotic Options
Authors: Fabry Pieter , Thomas David
Published: December 2017

This article presents a new method for Monte Carlo (MC) option pricing using field-programmable gate arrays (FPGAs), which use a discrete-space random walk over a binomial lattice, rather than the continuous space-walks used by existing approaches. The underlying hypothesis is that the discrete-space walk will significantly reduce the area needed for each MC engine, and the resulting increase in parallelisation and raw performance outweighs any accuracy losses introduced by the discretisation. Experimental results support this hypothesis, showing that for a given MC simulation size, there is no significant loss in accuracy by using a discrete space model for the path-dependent exotic financial options. Analysis of the binomial simulation model shows that only limited-precision fixed-point arithmetic is needed, and also shows that pairs of MC kernels are able to share RAM resources. When using realistic constraints on pricing problems, it was found that the size of a discrete-space MC engine can be kept to 370 Flip-Flops and 233 Lookup Tables, allowing up to 3,000 variance-reduced MC cores in one FPGA. The combination of a highly parallelisable architecture and model-specific optimisations means that the binomial pricing technique allows for a 50× improvement in throughput compared to existing FPGA approaches, without any reduction in accuracy.
Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis
Authors: May R. C. , Hara Y. , Kelly R. A. , Block K. P. , Buse M. G. , Mitch W. E.
Published: December 2017

Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH4Cl X 100 g body wt-1 X day-1. Epitrochlearis muscles were incubated with L-[1-14C]-valine and L-[1-14C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower (P less than 0.05) in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher (P less than 0.05) in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain alpha-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. We conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain alpha-keto acid dehydrogenase.
Gut-liver interaction in glutamine homeostasis: portal ammonia role in uptake and metabolism
Authors: Buttrose M. , McKellar D. , Welbourne T. C.
Published: December 2017

The role of ammonia released by the gut on hepatic glutamine handling and metabolism was studied in postabsorptive anesthesized male Sprague-Dawley rats at spontaneous and elevated arterial glutamine concentrations. Glutamine handling and metabolite release across both organ beds were studied using arteriovenous concentration differences and simultaneously measured portal and hepatic venous plasma flows. At the spontaneous arterial glutamine load, fractional glutamine extraction, FE-Gln, by the gut and the liver was 24 and 10%, respectively. At the elevated glutamine load, gut glutamine uptake doubled, while FE-Gln remained at 24%; however, portal ammonia and alanine increased and decreased, respectively. In response, hepatic FE-Gln increased to 28% with a large release of glutamate and urea. The role of portal ammonia in modulating hepatic glutamine uptake was studied by infusing NH4HCO3 directly into the portal vein. Increasing the portal load promptly stimulated hepatic glutamine uptake and glutamate and urea release. Mitochondria isolated from these livers produced more glutamate from glutamine, suggesting ammonia activation of hepatic glutaminase flux; in addition, citrulline formation increased, suggesting a coupling of glutaminase flux to urea synthesis. The results are consistent with portal ammonia release acting as a key informational molecule in interorgan glutamine flow.
A translational inhibitor from muscles of diabetic rats: identification as histone H1
Authors: O'Leary N. E. , Mehard W. B. , Cheema I. R. , Moore K. , Buse M. G.
Published: December 2017

A heat- and acid-stable protein fraction that inhibited peptide chain initiation in rabbit reticulocyte lysates was extracted from frozen, powdered rat skeletal muscles by stepwise trichloroacetic acid precipitation. Streptozotocin-induced diabetes increased the inhibitory activity; this was prevented by insulin therapy. Size-exclusion high-performance liquid chromatography resolved four inhibitory fractions; only one was consistently increased (approximately 2-fold) in muscle extracts from diabetic rats. Polysome profiles of lysates incubated with this fraction indicated peptide chain initiation inhibition. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified inhibitory fraction migrated with apparent Mr 30 and 32 kDa, which on Western blot immunostained with antisera against histone H1/H1(0). Perchloric acid extraction of muscle homogenates yielded approximately twofold more H1 from diabetic than from control rats; yield from diabetics decreased to control values 5 h after subcutaneous insulin injection. Inclusion of detergent during homogenization increased H1 yield more from muscles of control than from diabetic rats and abolished the difference between them. Because H1 affects several biochemical reactions, its facilitated extraction from insulin-deprived tissues can bias interpretation of studies of insulin action.
Comparison of glucose and glucose plus lipid as caloric sources in parenterally fed rats
Authors: Lanza-Jacoby S. , Tabares A. , Sitren H. S. , Kosar E.
Published: December 2017

This study investigated the etiology of fat infiltration of the liver during total parenteral nutrition. We measured the content of liver lipids, serum lipids, liver lipogenic enzymes, rates of in vivo fatty acid synthesis, and carcass composition in rats during continuous intravenous (iv) and intragastric (ig) feeding of two diets containing either 100% glucose or 75% glucose-25% lipid (20% Intralipid). Two groups of orally (O) fed rats were given solid diets similar to either the glucose or glucose-lipid solution in energy and nitrogen content. All six groups of rats (285-295 g) received 230 kcal X kg-1 X day -1 and 766 mg N X kg-1 X day-1. Total liver fat was greater after feeding the glucose diet ig rather than iv. However, feeding the glucose-lipid diet ig but not iv reduced the accumulation of liver fat by 49%. There were no differences in serum glucose concentrations among the three groups fed the glucose solution. Serum glucose concentrations in iv and O rats fed either diet were not significantly different; whereas feeding the glucose-lipid solution ig lowered serum glucose compared with the 100% glucose solution. Insulin concentrations were similar among all groups. The concentrations of serum triglycerides and cholesterol were higher in the groups fed the glucose-lipid diet. The activities of the liver lipogenic enzymes and rates of fatty acid synthesis were higher in iv- and ig-fed rats receiving the glucose diet compared with the glucose-lipid diet.(ABSTRACT TRUNCATED AT 250 WORDS)
A dual mechanism for regulation of kidney phosphate transport by parathyroid hormone
Authors: Cole J. A. , Eber S. L. , Poelling R. E. , Thorne P. K. , Forte L. R.
Published: December 2017

Regulation of phosphate transport by parathyroid hormone (PTH) was investigated in continuous lines of kidney cells. Phosphate transport was reduced by PTH-(1-34) at physiological concentrations (EC50 5 X 10(-11) M), whereas much higher concentrations were required to stimulate cAMP formation (EC50 1 X 10(-8) M) in opossum kidney (OK) cells. The PTH analogue [Nle]PTH-(3-34) also inhibited phosphate transport but did not enhance cAMP formation. Instead, [Nle]PTH-(3-34) was a competitive antagonist of PTH-(1-34) at cyclase-coupled receptors. PTH-(7-34) had no effect on phosphate transport or cAMP formation. Phorbol esters or mezerein were potent inhibitors of phosphate transport but did not affect cAMP synthesis. Their potencies paralleled the rank-order potency of these agents as activators of protein kinase c in other systems. Maximally effective concentrations of PTH-(1-34) and mezerein did not produce additive inhibition of phosphate transport in OK cells. Phorbol esters stimulated phosphate transport in JTC-12 cells, but PTH-(1-34) had no effect. We concluded that PTH regulates OK cell phosphate transport by interacting with two classes of receptors, and transmembrane-signaling mechanisms. Physiological levels of PTH-(1-34) may regulate phosphate transport by activation of protein kinase c, whereas higher concentrations appear to activate adenylate cyclase.
Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation
Authors: Bianco A. C. , Silva J. E.
Published: December 2017

We have examined the activity of three lipogenic enzymes [malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), and acetyl coenzyme A (CoA) carboxylase], the activity of the mitochondrial FAD-dependent alpha-glycerolphosphate dehydrogenase (alpha-GPD), and the mitochondrial concentration of uncoupling protein (UCP) in brown adipose tissue (BAT) of euthyroid and hypothyroid rats, both at room temperature and in response to acute cold stress. These enzymes and UCP are important for the thermogenic response of BAT in adaptation to cold. The basal level of the lipogenic enzymes was normal or slightly elevated in hypothyroid rats maintained at 23 degrees C, but the levels of alpha-GPD and UCP were markedly reduced. Forty-eight hours at 4 degrees C resulted in an increase in the activity of G-6-PD, acetyl-CoA carboxylase, and alpha-GPD and in the concentration of UCP both in euthyroid and hypothyroid animals, but the levels reached were invariably less in hypothyroid animals, indicating that thyroid hormone is necessary for a full metabolic response of BAT under maximal demands. Of all variables measured, the most affected was UCP (only one-fifth of the response of euthyroid rats to cold) followed by alpha-GPD (approximately 50% the euthyroid response). The administration of replacement doses of triiodothyronine (T3) to hypothyroid rats for 5-7 days did not normalize any of the BAT responses, whereas the replacement of thyroxine (T4) for only 2 days sufficed to normalize them all. This effect of T4 was abolished by preventing its conversion to T3 with iopanoic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM
Authors: Yki-Jarvinen H. , Kubo K. , Zawadzki J. , Lillioja S. , Young A. , Abbott W. , Foley J. E.
Published: December 2017

It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. We compared the sensitivities of glucose transport and antilipolysis to insulin and measured insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic (% fat, 41 +/- 1), 25 obese diabetic (% fat, 40 +/- 1), and 15 nonobese (% fat, 30 +/- 1) female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport and antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED50 for stimulation of glucose transport was higher in the obese patients with NIDDM (171 +/- 38 vs. 92 +/- 10 pM, P less than 0.005). In contrast, the ED50s for antilipolysis were similar in obese diabetic patients (32 +/- 6 pM) and obese nondiabetic subjects (27 +/- 3 pM). No difference was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder.
Maternal-fetal communication of circadian phase in a precocious rodent, the spiny mouse
Authors: Weaver D. R. , Reppert S. M.
Published: December 2017

The development of circadian rhythms was examined in a precocious rodent species, the spiny mouse. Spiny mouse pups born and reared in constant darkness expressed robust circadian rhythms in locomotor activity as early as day 5 of life. Free-running activity rhythms of pups born and reared in constant darkness were coordinated with the dam on the day of birth. Postnatal maternal influences on pup rhythmicity are minimal in this species, as pups fostered on the day of birth to dams whose circadian phases were opposite to the pups' original dams were coordinated with their original dams on the day of birth. Studies using 2-deoxy-D-[1-14C]-glucose autoradiography showed that there were synchronous (coordinated) rhythms in metabolic activity in the maternal and fetal suprachiasmatic nuclei, directly demonstrating prenatal coordination of maternal and fetal rhythmicity. Maternal-fetal coordination of circadian phase was not the result of direct entrainment of the fetuses to the environmental light-dark cycle. These results demonstrate that there is prenatal communication of circadian phase in this precocious species, without demonstrable postnatal maternal influences on pup circadian rhythmicity. Spiny mice therefore represent an important animal model in which circadian rhythms in the postnatal period can be used to precisely assess prenatal influences on circadian phase.
Regulation of mitochondrial adenine nucleotide content in newborn rabbit liver
Authors: Tullson P. C. , Aprille J. R.
Published: December 2017

This study examined the relationship between postnatal metabolic and hormonal changes and the accompanying rapid increase in mitochondrial adenine nucleotide content (ATP + ADP + AMP) in rabbit liver. The cytosolic NAD+/NADH concentration ratio, calculated from tissue pyruvate and lactate values, increased linearly 6.6-fold during the 1st postnatal h. The mitochondrial NAD+/NADH concentration ratio, calculated from tissue acetoacetate and beta-hydroxybutyrate values, increased 28-fold by 30 min postnatal. These changes in NAD+/NADH suggest that tissue oxygenation occurs rapidly and that oxygen supply rather than substrate supply is limiting for mitochondrial respiration in the immediate postnatal period. The normal increase in mitochondrial adenine nucleotide content that occurs within 2 h after birth was inhibited by hypoxia (5% O2). Glucagon stimulated the postnatal increase in mitochondrial adenine nucleotides but had no effect in combination with hypoxia. Both glucose and somatostatin injections inhibited the increase in mitochondrial adenine nucleotides and increased the insulin-to-glucagon ratio. Isoproterenol or dibutyryl cAMP stimulated, but propranolol did not inhibit, the normal increase in mitochondrial adenine nucleotide content. Phentolamine did not stimulate the postnatal accumulation of adenine nucleotides. In summary, the results show that the insulin-to-glucagon ratio is probably the most important hormone regulator of the rapid recompartmentation of adenine nucleotides into the mitochondrial matrix and that tissue oxygenation is strictly permissive for this hormone effect in the first 2 h after birth.
Definition of a prenatal sensitive period for maternal-fetal communication of day length
Authors: Weaver D. R. , Keohan J. T. , Reppert S. M.
Published: December 2017

The duration of the nocturnal elevation of melatonin in the dam is a key feature in providing the Djungarian hamster fetus with a prenatal photoperiodic history. The developing animal compares the prenatal photoperiod with the photoperiod experienced during the postnatal period to properly time puberty. In the present report, we define the period during gestation when melatonin administered to the dam is effective in providing the fetus with a prenatal photoperiodic history. The administration of melatonin (50 ng delivered over 10 h at night) by timed infusions to pregnant, pinealectomized Djungarian hamsters for the last 4-7 days of gestation stimulated testicular weights of male pups reared in 14 h of light/day. Single 10-h melatonin infusions were ineffective in stimulating reproductive development (testes weights on day 34) of the male pups, irrespective of the gestational age of the fetus at the time of treatment. In contrast, two consecutive nightly 10-h infusions during gestation clearly stimulated testicular development. The gestational age of the fetus at the time of infusion strongly influenced the response, however. Treatments beginning between 6 and 3 days before birth were effective in stimulating postnatal reproductive development of the offspring. These results indicate that there is a well-delineated, sensitive period during prenatal development when melatonin can provide the fetus with a prenatal photoperiodic history.
Delayed extra-adrenal epinephrine secretion after bilateral adrenalectomy in rats
Authors: Ricordi C. , Shah S. D. , Lacy P. E. , Clutter W. E. , Cryer P. E.
Published: December 2017

Regulated systemic extra-adrenal epinephrine secretion has been demonstrated in long-term bilaterally adrenalectomized humans. To determine whether this is demonstrable immediately after adrenalectomy and therefore presumably ongoing when the adrenal medullas are intact or if it develops over time after the adrenal medullas are removed, we measured plasma catecholamine concentrations before and serially after bilateral adrenalectomy with cortical reimplantation in rats. We found plasma epinephrine concentrations to decrease from 244 +/- 41 pg/ml to levels that were not convincingly detectable, using a single-isotope derivative assay with a detection limit of 10 pg/ml, for up to 1 wk after bilateral adrenalectomy with cortical reimplantation. Plasma epinephrine concentrations increased thereafter, becoming detectable in all animals and averaging 31 +/- 6 pg/ml 4 wk after adrenalectomy. Thus extra-adrenal epinephrine secretion appears to be a delayed response to removal of the adrenal medullas and cannot be assumed to be ongoing when the adrenal medullas are intact.
Relationship of substrate level to turnover rate in fasted adult and newborn dogs
Authors: Hulman S. , Kliegman R. , Heng J. , Crouser E.
Published: December 2017

Glucose turnover, clearance and response to insulin were determined in fasted newborn and adult dogs. Fasting levels of glucose and insulin and rates of glucose turnover and clearance were not different between the two groups. Blood glucose correlated with basal glucose turnover in newborn pups but not in adult dogs. Glucose turnover was not related to fasting plasma insulin levels. Glucose clearance was an inverse function of blood glucose levels among newborn but not adult dogs. Glucose clearance and blood glucose levels were not related to insulin concentrations. In response to euglycemic hyperinsulinemia, glucose metabolism increased 4-fold among adults but only 1.7-fold in pups. Hyperglycemic hyperinsulinemia increased glucose metabolism in both groups but to a much greater extent in the pups. Euglycemic hyperinsulinemia increased the metabolic clearance rate of glucose 4.2-fold among adults but only 1.8-fold in newborn dogs. In response to hyperglycemic hyperinsulinemia glucose clearance rates were now similar. Despite euglycemic hyperinsulinemia, the newborn dog had an attenuated response to insulin, demonstrating lower rates of glucose metabolism and glucose clearance. The response to the hyperglycemic stimuli suggests that maximal glucose uptake was not achieved during hyperinsulinemia alone. This response supports the concept of glucose-mediated regulation of glucose disposal in newborn animals.
Dissociation between plasma renin and plasma aldosterone induced by dietary glycine hydrochloride
Authors: Kotchen T. A. , Guthrie G. P. , Boucher L. D. , Lorenz J. N. , Ott C. E.
Published: December 2017

We evaluated the effects of selective dietary chloride loading (without sodium) on plasma renin activity (PRA) and plasma aldosterone in the sodium-deprived Sprague-Dawley rat. Three groups of animals were fed one of the following diets for 13 days: 1) low NaCl; 2) high NaCl; or 3) low sodium, high chloride, provided as glycine hydrochloride. Compared with NaCl-deprived animals, PRA and plasma aldosterone were lower (P less than 0.01) in animals fed low sodium high chloride, whereas aldosterone in animals fed glycine hydrochloride was higher (P less than 0.01) than that of NaCl-deprived animals. In contrast, plasma concentrations of corticosterone and 18-hydroxycorticosterone were not increased by selective chloride loading. Glycine chloride-fed animals were acidotic and had elevated plasma concentrations of potassium and ionized calcium. Thus stimulation of aldosterone by selective chloride loading is not related to PRA or ACTH but may be due to a direct effect of acidosis or an indirect effect of acidosis on potassium and/or calcium. Additionally, selective chloride loading appears to stimulate the conversion of 18-hydroxycorticosterone to aldosterone.
Insulin response of components of whole-body and muscle carbohydrate metabolism in humans
Authors: Young A. A. , Bogardus C. , Stone K. , Mott D. M.
Published: December 2017

We measured total body insulin-mediated glucose uptake, carbohydrate oxidation, storage (nonoxidative disposal), muscle glycogen synthase activity, and muscle glucose 6-phosphate (G-6-P) content in response to five levels of insulinemia (means 16, 52, 152, 573, and 5,550 microU/ml) in 16 male glucose-tolerant volunteers. Insulin dissociation constants (KDs) for disposal, storage, and synthase activity (but not for oxidation) are coincident, suggesting that storage via glycogen synthesis could be a major determinant of glucose disposal. Increases in glucose disposal were associated with decreases in muscle G-6-P concentration. These data suggest that the principal control over carbohydrate disposal is exerted after G-6-P. The coincidence of insulin sensitivities for disposal, storage, and synthase activity suggest that storage via glycogen synthesis could be a major determinant of glucose disposal.
Pharmacological characterization of two calcium currents in GH3 cells
Authors: Simasko S. M. , Weiland G. A. , Oswald R. E.
Published: December 2017

Whole cell patch-clamp techniques were used to investigate the pharmacological properties of calcium currents in the clonal rat pituitary cell line GH3. Current traces induced by a 100-ms pulse to 0 mV from a holding potential of -80 mV consisted of a component that rapidly inactivated during the pulse and a component that slowly inactivated during the pulse. When the holding potential was reduced to -32 mV, the rapidly inactivating component of the trace disappeared. The dihydropyridine calcium channel blocker nitrendipine affected only the slowly inactivating component of the trace. At a holding potential of -80 mV, nitrendipine blocked the slowly inactivating current with an IC50 of 1 microM. The IC50 for nitrendipine was found to be dependent on the holding potential, decreasing to 10 nM when the holding potential was -32 mV. The dihydropyridine agonist Bay-K 8644, like nitrendipine, affected only the slowly inactivating component. The inorganic blocker Cd2+ blocked both components but the slowly inactivating current was three- to fourfold more sensitive. These results are best explained by the existence of two types of calcium channels in these cells, one sensitive to dihydropyridines and one insensitive to dihydropyridines. These channels appear analogous to the T-type channel (inactivating current) and L-type channel (slowly inactivating current) described in other preparations.
Insulin release by glucagon and secretin: studies with secretin-glucagon hybrids
Authors: Kofod H. , Andreu D. , Thams P. , Merrifield R. B. , Hedeskov C. J. , Hansen B. , Lernmark A.
Published: December 2017

Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M) showed that the fold increase compared with glucose alone had the following ranking order: secretin = [Tyr10, Tyr13]-secretin 1.6 less than [Tyr10, Tyr13, Trp25]secretin 1.8 less than glucagon 1.9 less than [Asp3, Glu9, Arg12]glucagon 2.3 = [Asp3, Glu9]glucagon. These results suggest that despite similar potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different.
Inhibition by extracellular Na+ replacement of GRF-induced GH secretion from rat pituitary cells
Authors: Kato M. , Hattori M. A. , Suzuki M.
Published: December 2017

To further clarify the ionic mechanism of the action of growth hormone (GH)-releasing factor (hGRF) on GH secretion, the involvement of extracellular Na+ was studied in perifused dispersed rat anterior pituitary cells. Replacing extracellular Na+ with mannitol or tris(hydroxymethyl)aminomethane (Tris+) suppressed hGRF- and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-induced GH secretion. The peak responses to a 2-min application of 1 nM hGRF were 165.0 +/- 5.6 ng/ml (normal medium, mean +/- SE), 21.2 +/- 1.4 ng/ml (Na+-free, mannitol medium), and 18.0 +/- 1.7 ng/ml (Na+-free, Tris+ medium). GH secretion induced by DBcAMP was also suppressed by Na+ replacement to less than 50% of that in normal medium. However, either 15 or 30 mM KCl-stimulated GH secretion was not markedly affected by replacement of Na+ with either compound. Tetrodotoxin, a voltage-sensitive Na+ channel blocker, had no effect on either hGRF- or excess K+-induced GH secretion. cAMP production by hGRF was not greatly affected by replacing extracellular Na+. Thus extracellular Na+ plays an important role in hGRF-induced GH secretion, especially in the process after cAMP production. The involvement of cAMP-sensitive Na+ channels in hGRF-stimulated GH secretion is discussed.
1,25(OH)2D3 and Ca-binding protein in fetal rats: relationship to the maternal vitamin D status
Authors: Verhaeghe J. , Thomasset M. , Brehier A. , Van Assche F. A. , Bouillon R.
Published: December 2017

The autonomy and functional role of fetal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH)2D3 were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH)2D3 levels were correlated (r = 0.80; P less than 0.001). The vitamin D-dependent calcium-binding proteins (CaBP9K and CaBP28K) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP9K and CaBP28K in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH)2D3 levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP9K and renal CaBPs, but placental CaBP9K was not different. In diabetic pregnant rats, duodenal CaBP9K tended to be lower, while renal CaBPs were normal; placental CaBP9K was decreased. No significant changes in CaBP levels were observed in fetuses of low calcium-phosphorus diet rats or fetuses of diabetic rats. The results indicate that in the rat fetal 1,25(OH)2D3 depends on maternal 1,25(OH)2D3 or on factors regulating maternal 1,25(OH)2D3. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH)2D3 levels confirms earlier data showing that 1,25(OH)2D3 has a limited hormonal function during perinatal development in the rat.
Protein turnover in gravid and nongravid horns of uterus in pregnant rats
Authors: Goldspink D. F. , Douglas A. J.
Published: December 2017

Changes in uterine protein, RNA, and DNA contents in gravid and nongravid horns from the same animal were studied after 14 and 16 days of pregnancy. At 16 days, all of these parameters of growth had increased between three- and sevenfold in the gravid horn while remaining unchanged in the nongravid horn compared with the uterus of nonpregnant control animals. In the nongravid horn, the hormonal changes associated with pregnancy induced antagonistic decreases in both the average rates of protein synthesis and protein breakdown, with the net result being no change in its growth. In the gravid horn, however, the hormonal influences are coupled with the stretching effects produced by the enlarging fetuses. Here the net effect was a marked suppression of protein breakdown, resulting in a fourfold increase in its rate of growth. These data, together with those derived from analysis of both fetal and nonfetal sites from the gravid horn, led to the following conclusions. Changes in circulating hormones during pregnancy do not alone appear to influence the overall size of the uterus. In contrast, mechanical distension of the uterus promotes rapid and extensive growth.
Skeletal muscle glucose uptake during dynamic exercise in humans: role of muscle mass
Authors: Richter E. A. , Kiens B. , Saltin B. , Christensen N. J. , Savard G.
Published: December 2017

To study the role of muscle mass in glucoregulation, six subjects worked with the knee extensors of one leg on a specially constructed cycle ergometer. The knee extensors of one leg worked either alone or in combination with the knee extensors of the other leg and/or with the arms. Substrate usage was measured across both knee extensors by femoral arterial and venous catheterization and measurement of femoral venous blood flow. Glucose uptake by the working knee extensors was absolutely (by approximately 20%) or relatively decreased when arm cranking was added to knee extensions. The decrease in glucose uptake was not compensated for by increased uptake of free fatty acids but was accompanied by decreases in plasma insulin and increases in plasma epinephrine and norepinephrine. During work with large muscle masses, arterial lactate increased to approximately 6 mM, and net leg lactate release reverted to net lactate uptake. Decreased glucose uptake could not be explained by decreased perfusion. It is concluded that thigh muscle glucose uptake is affected by the size of the total muscle mass engaged in exercise. The decrease in thigh glucose uptake, when arm cranking was added and O2 uptake was increased above 50% of maximum aerobic capacity, may be elicited by neuroendocrine adjustments or lactate-induced inhibition of glycolysis and may represent a mechanism for protecting against premature hypoglycemia during prolonged exercise.
Modulation of receptor-mediated gonadotropin action in rat testes by dietary fat
Authors: Sebokova E. , Garg M. L. , Clandinin M. T.
Published: December 2017

The effect of feeding diets enriched with 18:2 omega 6, 18:3 omega 3, or saturated fatty acids on lipid composition and receptor-mediated action of luteinizing hormone/human chorionic gonadotropin (LH/hCG) in rat testicular plasma membranes was investigated. Linoleic and alpha-linolenic acid treatments reduced total phospholipid and cholesterol content of the testicular plasma membrane and altered membrane phospholipid composition. Change in phospholipid and cholesterol content after feeding the polyunsaturated fats decreased cholesterol to phospholipid ratios and binding capacity of the LH/hCG receptor in the testicular plasma membrane. LH-stimulated adenylate cyclase activity was decreased in animals fed the linolenic acid-rich diet. NaF-stimulated adenylate cyclase activity was decreased in animals fed diets high in either polyunsaturated fatty acid. Decreased plasma membrane LH/hCG receptor content was associated with decreased testosterone production in Leydig cells in response to LH in the linolenic acid-fed group. It is suggested that change in cholesterol-to-phospholipid ratios alters the physical properties of testicular plasma membranes in a manner that influences accessibility of LH/hCG receptors in testicular tissue.
Angiotensin II receptors in rabbit renal preglomerular vessels
Authors: Brown G. P. , Venuto R. C.
Published: December 2017

Controversy exists regarding the specific sites within the renal microcirculation affected by angiotensin II (ANG II). Under some conditions, ANG II can elicit direct vasoconstrictor responses in the preglomerular vessels and efferent arterioles. These experiments were designed to evaluate the binding of 125I-ANG II in preglomerular vessels. Arcuate and interlobular arteries, with attached proximal segments of afferent arterioles, were microdissected from rabbit renal cortexes. A membrane preparation was obtained from the pooled freshly dissected vessels and utilized in an ANG II radioreceptor assay on the same day. Binding site concentrations [N] and dissociation constants [KD] were obtained by Scatchard analyses of binding inhibition data. Specific binding was saturable and reversible. The dissociation of bound ANG II was enhanced in the presence of a nonhydrolyzable analogue of GTP. Linear Scatchard plots were obtained, indicating the presence of a single class of high-affinity binding sites. The KD and N are similar to those for ANG II receptors in extrarenal vascular tissue. The order of binding inhibition potencies of ANG analogues was [Sar1,Ile8]-ANG II much greater than [Sar1,Ala8]ANG II = ANG II = ANG III much greater than ANG I, which is consistent with in vivo observations of the effects of these analogues on renal blood flow. The binding inhibition potencies of ANG III and [Sar1,Ile8]ANG II were greater in renal compared with reported values for extrarenal vasculature and rabbit glomeruli. Furthermore, there were no differences in ANG II receptor parameters in preglomerular vessels obtained from pregnant and nonpregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian rhythm in sensitivity of glucose metabolism to insulin in rat soleus muscle
Authors: Leighton B. , Kowalchuk J. M. , Challiss R. A. , Newsholme E. A.
Published: December 2017

This study determined whether the sensitivity of glucose metabolism to insulin in skeletal muscle varies during a 24-h period. Soleus muscles were isolated from ad libitum-fed rats killed at 0900, 1600, 2100, and 0300. The animal house was illuminated between 0800 and 2000. The sensitivities of glycolysis (which is an excellent index of glucose transport) and glycogen synthesis to insulin were greatest in muscles isolated at 0900 and 2100. Marked decreases in sensitivities of both processes to insulin were observed in muscles isolated at 0300 and 1600, which are times halfway through the feeding and postabsorptive periods, respectively. Hence, this study demonstrates circadian changes in the sensitivity of glucose utilization by skeletal muscle to insulin, which may be important in control of blood glucose concentration. Glycogen levels in skeletal muscles were highest at 0300 and lowest at 2100; hepatic glycogen content reached a peak at 0900, and the lowest content was measured at 2100. The liver glycogen level was increased by only 15% midway into the feeding period (i.e., 0300). This suggests that muscle glycogen may act as a temporary store of glucose residues during the feeding period; it stores glycogen in the first half of the feeding period but during the second half some muscle glycogen is converted to lactate, which acts as a precursor for hepatic gluconeogenesis.
Relationship between glutamine concentration and protein synthesis in rat skeletal muscle
Authors: Jepson M. M. , Bates P. C. , Broadbent P. , Pell J. M. , Millward D. J.
Published: December 2017

Muscle glutamine concentration ([GLN]) and protein synthesis rate (Ks) have been examined in vivo in well-fed, protein-deficient, starved, and endotoxemic rats. With protein deficiency (8 or 5% casein diet), [GLN] fell from 7.70 to 5.58 and 3.56 mmol/kg in the 8 and 5% diet groups, with Ks falling from 15.42 to 9.1 and 6.84%/day. Three-day starvation reduced [GLN] and Ks to 2.38 mmol/kg and 5.6%/day, respectively. In all these groups food intakes and insulin were generally well maintained (except in the starved group), whereas free 3,5,3'-triiodothyronine (T3) was depressed in the starved and 5% protein group. The E. coli lipopolysaccharide endotoxin (3 mg/kg) reduced [GLN] to 5.85 and 4.72 mmol/kg and Ks to 10.5 and 9.10%/day in two well-fed groups. Insulin levels were increased, and free T3 levels fell. Combined protein deficiency and endotoxemia further reduced [GLN] and Ks to 1.88 mmol/kg and 4.01%/day, respectively, in the 5% protein rats. Changes in both ribosomal activity (KRNA) and concentration (RNA/protein) contributed to the fall in Ks in malnutrition and endotoxemia, although reductions in the RNA concentration were most marked with protein deficiency and reductions in the KRNA dominated the response to the endotoxin. The changes in [GLN] and Ks were highly correlated as were [GLN] and both KRNA and the RNA concentration, and these relationships were unique to glutamine. These relationships could reflect sensitivity of glutamine transport and protein synthesis to the same regulatory influences, and the particular roles of insulin and T3 are discussed, as well as any direct influence of glutamine on protein synthesis.
Very-low-density lipoprotein triglyceride kinetics in acute and chronic carbohydrate-fed rats
Authors: Hirano T. , Mamo J. , Poapst M. , Steiner G.
Published: December 2017

Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in rats maintained on either chow and water (control) or chow and a 10% carbohydrate drinking solution (fructose or glucose). The hexose solutions were available for an acute (16 h) or chronic (14 day) period. The acute fructose (AF), acute glucose (AG), and chronic fructose (CF) groups were hypertriglyceridemic (HTG) compared with control. Plasma TG concentration in chronic glucose (CG)-fed rats was similar to control. VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The fractional catabolic rate (FCR) was then determined by monitoring the clearance of plasma [3H]VLDL-TG in recipient animals. Donors and recipients were treated in an identical manner. AF and CF groups had an FCR significantly lower than rats given glucose for comparable periods. Both fructose groups and the AG group also had a lower FCR than control. In contrast, FCR in the CG group was significantly higher than controls. TG production rate (TGPR) in both AF and CF fed rats did not significantly differ from controls, suggesting that the HTG observed in these animals was solely from a catabolic defect. AG- and CG-treated glucose animals both had TGPR significantly higher than controls. Therefore, overproduction of VLDL-TG contributed to the HTG associated with this carbohydrate.
Effect of alpha- and beta-adrenergic stimulation on atrial natriuretic peptide release in vitro
Authors: Wong N. L. , Wong E. F. , Au G. H. , Hu D. C.
Published: December 2017

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was studied using the isolated left and right atria from a rat. The atria were perfused with Tyrode's solution, equilibrated with 95% O2-5% CO2 at 37 degrees C with a constant flow of 0.5 ml/min. Addition of epinephrine (10(-6) M), an alpha- and beta-agonist, to the perfusate induced the biphasic release of ANP from the right atrium without effect on the left. The initial peak (19.2 +/- 2.6 pg.min-1.ml-1) occurs 2-4 min after the administration of epinephrine, which lasted 4-6 min and returned to base line (10.4 +/- 1.1 pg.min-1.mg-1). The second peak (16.5 +/- 2.0 pg.min-1.ml-1) appeared 30-35 min after epinephrine administration and was sustained for 100 min, at which time the experiment was terminated. The first peak was stimulated by isoproterenol (10(-6) M), a beta-agonist, and blunted by propranolol (10(-6) M), a beta-antagonist. The second peak appeared following methoxamine (10(-6) M), an alpha-agonist, and could be suppressed by phentolamine (10(-6) M), an alpha-antagonist. These studies indirectly suggest that the adenosine 3',5'-cyclic monophosphate system and the inositol triphosphate system are involved in ANP secretion, with the former responsible for the initial rapid release and the latter maintaining the secretion.