bluuebunny/crossref_metadata_2025 huggingface dataset:
Standards for UNiversal reporting of patient Decision Aid Evaluation studies: the development of SUNDAE Checklist
Authors: Sepucha Karen R , Abhyankar Purva , Hoffman Aubri S , Bekker Hilary L , LeBlanc Annie , Levin Carrie A , Ropka Mary , Shaffer Victoria A , Sheridan Stacey L , Stacey Dawn , Stalmeier Peep , Vo Ha , Wills Celia E , Thomson Richard
Published: December 2017

Background

Patient decision aids (PDAs) are evidence-based tools designed to help patients make specific and deliberated choices among healthcare options. The International Patient Decision Aid Standards (IPDAS) Collaboration review papers and Cochrane systematic review of PDAs have found significant gaps in the reporting of evaluations of PDAs, including poor or limited reporting of PDA content, development methods and delivery. This study sought to develop and reach consensus on reporting guidelines to improve the quality of publications evaluating PDAs.

Methods

An international workgroup, consisting of members from IPDAS Collaboration, followed established methods to develop reporting guidelines for PDA evaluation studies. This paper describes the results from three completed phases: (1) planning, (2) drafting and (3) consensus, which included a modified, two-stage, online international Delphi process. The work was conducted over 2 years with bimonthly conference calls and three in-person meetings. The workgroup used input from these phases to produce a final set of recommended items in the form of a checklist.

Results

The SUNDAE Checklist (Standards for UNiversal reporting of patient Decision Aid Evaluations) includes 26 items recommended for studies reporting evaluations of PDAs. In the two-stage Delphi process, 117/143 (82%) experts from 14 countries completed round 1 and 96/117 (82%) completed round 2. Respondents reached a high level of consensus on the importance of the items and indicated strong willingness to use the items when reporting PDA studies.

Conclusion

The SUNDAE Checklist will help ensure that reports of PDA evaluation studies are understandable, transparent and of high quality. A separate Explanation and Elaboration publication provides additional details to support use of the checklist.
Introducing forensic entomology in cases of suspected animal neglect
Authors: McGarry John , Ratsep Emily , Ressel Lorenzo , Leeming Gail , Ricci Emanuele , Verin Ranieri , Blundell Richard , Kipar Anja , Hetzel Udo , Yeates James
Published: December 2017

Cases of arthropod‐infested, abandoned or abused animals are sometimes brought to the attention of veterinarians by animal welfare authorities, with the requirement for a full postmortem examination towards criminal or civil proceedings. In these situations, entomology is an important support tool for the pathologists’ investigation since the presence of arthropod life cycle stages serve as reliable forensic markers, especially for blowflies which form the first waves of activity following death. In the present study, 70 cadavers from a total of 544 referred to the Institute of Veterinary Science, University of Liverpool, between 2009 and 2014 displayed evidence of infestation. Here, the authors introduce principles of applied entomology and simplified approaches for estimating the minimum time since death, relevant in the context of routine submissions and the broad remit of individual cases. Despite often limited availability of scene of the crime and local thermal data, the interpretation of the minimum postmortem interval has nonetheless proved valuable as an adjunct to the expert pathology report. However, future developments and enhanced accuracy in this area of animal welfare require resource and training in expertise, and agreed standardisation of both laboratory and field procedures.
Air-propelled abrasive grit can damage the perennial weed quackgrass
Authors: Forcella Frank , Humburg Daniel , Wortman Samuel E. , Clay Sharon A.
Published: December 2017

New techniques are needed to control quackgrass in organic crops. With ≥2 applications of abrasive air-propelled (800 kPa) corncob grit to 15-cm-tall quackgrass tillers, regrowth was minimal at 5 wk after treatment. Abrasive grits may be effective tools to help manage perennial weeds in organic row crops.
Genome-wide searches and molecular analyses highlight the unique evolutionary path of flavone synthase I (FNSI) in Apiaceae
Authors: Wang Qi-Zhi , Downie Stephen R. , Chen Zhen-Xi
Published: December 2017

Flavone synthase is a key enzyme for flavone biosynthesis and is encoded by two gene families: flavone synthase I (FNSI) and flavone synthase II (FNSII). FNSII is widely distributed in plants, while FNSI has been reported in rice (Oryza sativa) and seven species of Apiaceae. FNSI has likely evolved from the duplication of flavanone 3β-hydroxylase (F3H). In this study, we used multiple bioinformatics tools to identify putative FNSI and F3H genes from 42 publicly available genome and transcriptome datasets. Results showed that rice FNSI does not share a common ancestral sequence with other known FNSI genes and that FNSI is absent from species outside of Apiaceae. Positive selection site identification analysis revealed that four sites within the FNSI tree branches of Apiaceae evolved under significant positive selection. The putative F3H genes identified in this study provide a valuable resource for further function analysis of flavone synthase.
Whole-genome sequencing reveals the extent of heterozygosity in a preferentially self-fertilizing hermaphroditic vertebrate
Authors: Lins Luana S.F. , Trojahn Shawn , Sockell Alexandra , Yee Muh-Ching , Tatarenkov Andrey , Bustamante Carlos D. , Earley Ryan L. , Kelley Joanna L.
Published: December 2017

The mangrove rivulus, Kryptolebias marmoratus, is one of only two self-fertilizing hermaphroditic fish species and inhabits mangrove forests. While selfing can be advantageous, it reduces heterozygosity and decreases genetic diversity. Studies using microsatellites found that there are variable levels of selfing among populations of K. marmoratus, but overall, there is a low rate of outcrossing and, therefore, low heterozygosity. In this study, we used whole-genome data to assess the levels of heterozygosity in different lineages of the mangrove rivulus and infer the phylogenetic relationships among those lineages. We sequenced whole genomes from 15 lineages that were completely homozygous at microsatellite loci and used single nucleotide polymorphisms (SNPs) to determine heterozygosity levels. More variation was uncovered than in studies using microsatellite data because of the resolution of full genome sequencing data. Moreover, missense polymorphisms were found most often in genes associated with immune function and reproduction. Inferred phylogenetic relationships suggest that lineages largely group by their geographic distribution. The use of whole-genome data provided further insight into genetic diversity in this unique species. Although this study was limited by the number of lineages that were available, these data suggest that there is previously undescribed variation within lineages of K. marmoratus that could have functional consequences and (or) inform us about the limits to selfing (e.g., genetic load, accumulation of deleterious mutations) and selection that might favor the maintenance of heterozygosity. These results highlight the need to sequence additional individuals within and among lineages.
Interactions of intestinal lymph flow and secretion.
Authors: Granger D N , Mortillaro N A , Taylor A E
Published: December 2017

The relationship between lymph flow and intestinal secretion was studied in an isolated, vascularly perfused cat ileal preparation in which secretion was caused by three different means: 1) plasma dilution from a constant infusion of Tyrode solution (2.5 ml/min per kg), 2) elevation of intestinal venous pressure to 30 mmHg, and 3) exposure to cholera toxin. In the plasma-dilution group, lymph flow attained a peak value of 38 times control at 60-90 min following the onset of the infusion, after which time lymph flow progressively decreased. Concomitant to the rapid decrease in lymph flow was a rapid increase in intestinal secretion (filtration secretion). A similar pattern, i.e., a rapid increase in lymph flow followed by a progressive decrease in lymph flow and concomitant increase in filtration secretion, was observed in the venous hypertension group; however, peak lymph flow (20 X control) was observed within 10 min of the pertubation. No correlation between the onset of intestinal secretion and a decline in lymph flow was observed in the cholera toxin group.
Influence of hepatic taurine concentration on bile acid conjugation with taurine.
Authors: Hardison W G , Proffitt J H
Published: December 2017

In vitro, addition of taurine to liver homogenates increases the proportion of cholic acid conjugated with taurine. In the present study, the relation between hepatic taurine concentration and the proportion of infused sodium cholate conjugated with taurine was studied in the whole organ. The isolated perfused liver was studied to eliminate possible transfer of taurine to or from the large extrahepatic poosl present in vivo. During cholate infusion, the proportion of taurocholate excreted in bile decreased, and the proportion of glycocholate increased in a complementary fashion. Infusion of taurine with cholate prevented these changes. Hepatic taurine concentration, calculated from measured hepatic taurine concentrations before and at the end of cholate infusion, fell. Fall in proportion of total bile acid excreted as taurocholate was most rapid at low hepatic taurine concentrations between about 1.4 and 0.65 mumol/g liver. Hepatic taurine concentrations is a major determinant of the proportion of bile acid conjugated with taurine.
Further evidence for a central regulation of free fatty acid mobilization in the rat.
Authors: Gross J L , Migliorini R H
Published: December 2017

Previous studies have shown that anterior hypothalamic deafferentation in rats completely suppresses the increase in plasma free fatty acid (FFA), but not the hyperglycemia induced by administration of 2-deoxyglucose, suggesting a specific central regulation of FFA mobilization. The physiological importance of this finding was further investigated by examining in deafferented rats the response to several stimuli that modify the rate of lipomobilization in normal rats. The results show that the hypothalamic lesion interferes with FFA mobilization mainly when increased sympathetic activity is required: during cold exposure or forced muscular activity, and after insulin-induced hypoglycemia or a relatively long period of fasting. Changes in blood sugar responses, when observed, could be interpreted as secondary to an initial block in FFA mobilization. The data support our hypothesis that there are areas in the central nervous system sensitive to glycopenia and activated in situations requiring rapid mobilization of metabolic reserves that can specifically influence FFA mobilization through an activation of the sympathetic fibers of adipose tissue.
Relationship between plasma and cerebrospinal fluid insulin levels of dogs.
Authors: Woods S C , Porte D
Published: December 2017

Several experiments are reported in which insulin or glucose was administered intravenously to anesthetized dogs. Plasma and cerebrospinal fluid levels of glucose and immunoreactive insulin were determined at several intervals before and after the administrations. Intravenous insulin (0.2 U/kg) administered as either a pulse or a 1-h infusion caused a large increase of plasma insulin, but a relatively small increase of cerebrospinal fluid insulin. When endogenous insulin was elevated by the administration of glucose (100 mg/kg), cerebrospinal fluid insulin changed only slightly. A significant correlation was found between steady-state plasma and CSF endogenous insulin levels. The results are interpreted to indicate that the level of insulin in the cerebrospinal fluid reflects basal plasma level plus an integral over time of the insulin response to challenge. The implications of such a system are discussed.
Vasopressin in cerebrospinal fluid and plasma of man, dog, and rat.
Authors: Dogterom J , van Wimersma Greidanus T B , De Wied D
Published: December 2017

Arginine-8-vasopressin (AVP) levels were measured by a sensitive and specific radioimmunoassay (RIA) in plasma and cerebrospinal fluid (CSF) of three species man, dog, and rat (Wistar and the Brattleboro strain). Basal plasma values were 1.7 pg/ml in Wistar rat, and 2.4 pg/ml in dog. Pentobarbitone, used as anesthetic during collection of CSF from dog and rat, caused a significant rise of plasma AVP values in Wistar rats, but not in dogs. After withdrawal of CSF, the plasma AVP levels of Wistar rats were increased to 29.5 +/- 9.5 pg/ml, whereas the CSF levels from the same animals were 11.5 +/- 3.9 pg/ml. The response to the various stimuli was similar in Brattleboro rats, heterozygous for hereditary hypothalamic diabetes insipidus, and in Wistar rats. In Brattleboro rats, homozygous for hereditary hypothalamic diabetes insipidus, AVP was neither detectable in plasma nor in CSF. In dog and man, AVP levels in CSF samples were higher than in simultaneously obtained plasma samples. The possibility that AVP present in CSF, might be released directly from the synthetizing hypothalamic nuclei into the ventricular system is discussed.
Evidence for pyloropancreatic reflux for pancreatic exocrine secretion.
Authors: Debas H T , Yamagishi T
Published: December 2017

In seven dogs provided with innervated pouch of the pyloric antrum, gastric fistula, and chronic pancreatic fistula, the effect of graded antral distenion on pancreatic exocrine secretion was studied. The effect of antral distension was tested both when gastrin release was promoted (alkaline distention) and when gastrin release was blocked (acid distension). These studies were performed both before and after transthoracic truncal vagotomy. Graded alkaline antral distension caused graded rise in protein-rich pancreatic secretion and graded increase in the concentration of serum immunoreactive gastrin. A similar pancreatic response was also seen with graded acid distention although this time no rise in serum gastrin concentration occurred. Pancreatic response to antral distension with either alkali or acid is completely inhibited by pretreatment of the animals with systemic atropine. Truncal vagotomy reduced pancreatic response to alkaline antral distension by 90% but completely abolished pancreatic response to distension of the antrum with acid. These studies provide evidence for a pyloropancreatic reflex mechanism for pancreatic secretion that is cholinergic and requires intact long vagal pathways.
Hyperglycemic action of synthetic C-terminal fragments of human growth hormone.
Authors: Ng F M , Bornstein J
Published: December 2017

The synthetic peptides corresponding to amino acids 172-191, 176-191, 177-191, 178-191, 179-191, and 180-191 of human growth hormone (hGH) have been studied for their in vivo effects in normal rats. Four of the peptides (hGH 172-191, 176-191, 177-191, and 178-191) produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin, whereas the other two (hGH 179-191 and 180-191) were inert in the systems tested. A single dose (5 nmol/kg body wt) of the peptides containing the amino acids sequence 178-191 of the hGH molecule significantly reduced insulin sensitivity of the animals in intravenous insulin tolerance tests. The findings also indicate that the biologically active peptides must not only have the minimum of the informational sequence but also that this must be in correct physical configuration.
Glucoprivic feeding behavior in absence of other signs of glucoprivation.
Authors: Ritter R C , Roelke M , Neville M
Published: December 2017

When rats were denied immediate access to food after subcutaneous injection of 2-deoxy-D-glucose (2DG), the glucoprivically induced sympathoadrenal hyperglycemia subsided spontaneously within 6 h. However, if food was returned to the rats 6 h after 2DG injection, they still ate significantly more than after saline control injections. Rats injected with insulin also increased their feeding even when food was withheld until the animals had returned to normoglycemia. Injections of exogenous glucose sufficient to elevate blood glucose concentrations above normal failed to inhibit increased feeding observed when food was returned 6 h after injection of regular insulin. These data show that 2DG and insulin-induced feeding can occur in the absence of overt signs of glucoprivation and suggest that the glucoprivic control may be operable in the day-to-day control of feeding when other signs of glucoprivation are not readily observable.
Plasma amino acid turnover rates and pools in rabbits: in vivo studies using stable isotopes.
Authors: Nissim I , Lapidot A
Published: December 2017

Gas chromatography--mass spectrometry of plasma amino acids has been used to determine the 15N enrichments of plasma glycine and alanine in rabbits in different metabolic states. Isotope-enrichment time-decay curves of plasma amino acids were linear over the course of the measurements after intravenous administration of a single dose of 15N-amino acid. Glycine and alanine pools and turnover rate constants were estimated from decay data. The effects of diurnal variation and fasting on glycine and alanine pool sizes, turnover rates, and flux in rabbits were studied to provide information on the effect of metabolic stress on amino acid kinetics in the whole body. The observations suggests that the transport of systemic glycine or alanine into the hepatocyte is under the control of a regulatory mechanism that compensates for decrease in the extracellular levels of the amino acids by enhancing the activity of the transport system. The volumes of the glycine and alanine pools were found to correspond to the extracellular space of rabbits, and the glycine and alanine pools can be identified as extracellular. We conclude that the plasma glycine and alanine 15N isotope-enrichment time-decay curves over the 1st h after a single intravenous dose of the amino acid represent mainly the hepatic uptake of glycine and alanine from the extracellular pool.
Effects of celiac and superior mesenteric ganglionectomy on interdigestive myoelectric complex in dogs.
Authors: Marlett J A , Code C F
Published: December 2017

The interdigestive myoelectrical activity of the stomach and small bowel has been studied before and after celiac and superior mesenteric ganglionectomy in four healthy, well-trained conscious dogs. The interdigestive myoelectric complex was present before and after the gangliomectomy in all dogs, but variability in the duration of its cycles was increased by ganglionectomy. The percentage of time that action potential activity was present during the interdigestive period in the stomach and orad half of the small bowel was also increased in all animals after the ganglionectomy. The duration of phase III, the activity front, was unaltered by the operation, but the timing of the other phases became more variable after ganglionectomy. The time required for migration of the complex from duodenum to terminal ileum was more variable after ganglionectomy in the three animals in which it could be measured, and in two of them the migration time was shorter. An abnormal electrical pattern occurred in all animals after ganglionectomy. Its duration ranged from 0.5--5 min. Electrically, it appeared to represent an elongated, nonmigrating activity front.
Effect of ACTH on the aldosterone response to potassium in sheep with adrenal transplants.
Authors: Lun S , Espiner E A , Hart D S
Published: December 2017

The importance of physiological ACTH stimulation in maintaining the response of aldosterone secretion to potassium was studied in 5 conscious sheep with cervical adrenal autotransplants. Endogenous ACTH secretion was suppressed by dexamethasone. Constant local infusions of potassium that raised adrenal venous plasma by 2 mmol/l increased aldosterone secretion from 3 +/- 1 ng/min (mean +/- SE) to levels of 50 +/- 13 ng/min at 30 min, after which secretion fell to 14 +/- 6 ng/min at 230 min. Addition of submaximal ACTH (0.04 - 0.10 mU/min) to potassium infusions produced similar responses at 0--130 min, but aldosterone secretion increased at 130--190 min and was more sustained (40 +/- 9 ng/min at 230 min; P less than 0.05). Infusions of submaximal ACTH alone did not significantly increase aldosterone secretion above basal levels. Infusions of maximal ACTH (16.6 mU/min) produced higher aldosterone secretion in the group given ACTH replacement. These results show that the aldosterone response to potassium is phasic and poorly sustained in the absence of ACTH. Responsiveness can be restored by doses of ACTH insufficient alone to stimulate aldosterone secretion.
Effects of bilirubin on fat cell metabolism and lipolysis.
Authors: Shepherd R E , Moreno F J , Cashore W J , Fain J N
Published: December 2017

Bilirubin (0.45 mM) inhibited lipolysis and stimulated [1-14C]glucose oxidation by rat fat cells in the presence of an equimolar concentration of bovine serum albumin. Bilirubin was an insulinlike agent with respect to inhibition of lipolysis and stimulation of glucose oxidation. There was a marked inhibition of adenylate cyclase activity of fat cell ghosts by 0.001--0.1 mM bilirubin in the absence of albumin, which was largely reversed by the addition of albumin. Although both bilirubin and free fatty acids bind to albumin, the primary binding sites appear to be separate. The effects of bilirubin at a molar ratio to albumin of 2 or less were not influenced by free fatty acid-to-albumin ratios up to 3. Triglyceride lipase activity of partially purified rat fat cell homogenates was inhibited by bilirubin in the presence of an equimolar concentration of bovine albumin. These data indicate that the antilipolytic action of bilirubin is probably due to direct inhibition of triglyceride lipase through a mechanism that does not involve competition with free fatty acids for binding to albumin.
Turnover of total proteins and ornithine aminotransferase during liver regeneration in rats
Authors: Augustine S. L. , Swick R. W.
Published: December 2017

The recovery of approximately 40% of the total liver protein during the first day after partial hepatectomy was shown to be due to the near cessation of protein breakdown rather than to an increase in protein synthesis. The decrease in degradation of total protein was less if rats were adrenalectomized or protein-depleted prior to partial hepatectomy. The effect of these treatments originally suggested that changes in free amino acid levels in liver might be related to the rate of protein degradation. However, no correlation was found between levels of total free amino acids and rates of breakdown. Measurements of individual amino acids during liver regeneration suggested that levels of free methionine and phenylalanine, amino acids that have been found to lower rates of protein degradation in vitro, are not correlated with rates of breakdown in vivo. The difference between the fractional rate of ornithine aminotransferase degradation (0.68/day and 0.28/day in sham-hepatectomized and partially hepatectomized rats, respectively) was sufficient to account for the higher level of this protein 3 days after surgery in the latter group.
Effect of osmolality on arginine vasopressin and renin release after hemorrhage
Authors: Weitzman R. E. , Reviczky A. , Oddie T. H. , Fisher D. A.
Published: December 2017

The effects of alterations of plasma osmolality on plasma arginine vasopressin (AVP) and renin activity (PRA) following graded hemorrhage were studied in conscious dogs who were either euhydrated, dehydrated, water loaded, or infused with hypertonic saline. Base-line plasma osmolality and AVP were significantly different in the four treatment groups; however, following hemorrhage the increases in log AVP did not significantly differ. An unexpected finding was that water loading resulted in significant elevations in PRA and plasma aldosterone concentrations, whereas plasma osmolality and AVP were reduced. Prior to hemorrhage, PRA was significantly greater in the water-loaded and dehydrated groups than in the euhydrated or saline-infused groups; following hemorrhage the increases in log PRA were not significantly different in all four treatment groups. The data suggest that, although alterations in osmolality influence base-line levels of AVP, they have no effect on relative (logarithmic) rises in AVP following hemorrhage. Similarly, alterations in AVP may influence base-line PRA, but do not influence relative rises in PRA following hemorrhage.
Influence of the insulin-to-growth hormone ratio on body composition of mice
Authors: Mendel V. E.
Published: December 2017

To determine whether the insulin-to-growth hormone ratio was different in genetically related animals with known differences in food intake and amount of adipose tissue the following parameters were measured in lean (C57BL/6J) and yellow obese mice (Avy/a): food intake, body composition, energy intake, plasma concentrations, and ratios of insulin and growth hormone; these were determined in one experiment during a 24-h period. Yellow obese mice contained significantly greater amounts of body fat than the lean littermates, a significantly higher insulin-to-growth hormone ratio, and a higher daily food intake. In a second experiment, a shift in hormone concentrations and ratios occurred with increasing age and simultaneously with changes in body composition in the Avy/a mice; both changed without changes of food intake. The increased obesity may have resulted from an increase in the insulin-to-growth hormone ratio or more probably from an increase in the insulin level alone.
Evidence for a sexual variation in production of a hepatic erythropoietic factor by hepatectomized rats
Authors: Naughton B. A. , Liu P. , Kolks G. A. , Arce J. M. , Piliero S. J. , Gordon A. S.
Published: December 2017

Erythropoietin (Ep) is a glycoprotein hormone that is responsible for mammalian red blood cell production. Adult rat liver regenerating 48-72 h after hepatectomy (hepx) produces elevated levels of Ep in response to hypoxia when compared to sham-operated, anephric hypoxic controls. A factor, termed hepatopoietin (Hp), found in the serum of hepx rats, is capable of stimulating hepatic Ep production when administered to normal rats 18 h prior to hypoxic exposure. Although the hepatic vein is the most potent source of this factor, Hp can also be demonstrated in the systemic arterial circulation. Bilateral nephrectomy (nephrx) of the donor hepx animal 24 h prior to bleeding abolishes this variation, and highest Ep levels are noted when serum from a hepx and nephrx rat is administered to animals immediatley after nephrx and 18 h before hypoxic exposure. Serum derived from hepx male rats displays a greater ability to evoke hepatic Ep production in normal recipients than serum from similarly treated female rats. Regardless of the sex of the hepx donor, Ep elaboration after hypoxia is highest in male recipients. The results indicate that there is a sexual variation in the production of Hp as well as Ep.
Development of obesity in Zucker obese (fafa) rat in absence of hyperphagia
Authors: Cleary M. P. , Vasselli J. R. , Greenwood M. R.
Published: December 2017

The free-feeding, genetically obese rat is hyperphagic, hyperinsulinemic, and hypertriglyceridemic and has increased fat cell size and number compared to its lean littermate. These experiments demonstrate that, when fafa rats are prevented from expressing hyperphagia throughout life, the complete obese "syndrome" still develops. Furthermore, life-long food restriction does not prevent increased lipoprotein lipase in the fafa rat. The data support the concept that a peripheral metabolic adaptation, probably in lipid metabolism, results in preferential shunting of dietary substrate in the restricted obese rats to adipose tissue with concomitant decreases in other tissues.
Effect of serum sex steroids on pituitary LH response to LHRH and LH synthesis
Authors: Tang L. K.
Published: December 2017

To determine the factors responsible for the sex difference in luteinizing hormone (LH) response to luteinizing hormone-releasing hormone (LHRH) observed earlier in pituitary cultures, we examined the effects of serum, 17 beta-estradiol, and testosterone on pituitary LHRH-responsiveness and LH synthesis. Cultures prepared from female rats were maintained in medium supplemented with serums. Dextran-coated charcoal (DCC) adsorption of female rat serum reduced, whereas DCC adsorption of male rat serum increased the pituitary LHRH-responsiveness, indicating the existence of stimulatory factor(s) in female rat serum and inhibitory factor(s) in male rat serum. Readdition of testosterone to DCC female rat serum significantly reduced LH release in response to LHRH (78-32% of the control) without affecting total LH content. Readdition of 17 beta-estradiol to DCC female rat serum significantly increased the LH release in response to LHRH, cellular LH content, and 3H-labeled precursor uptake and incorporation into immunoprecipitable LH. These results indicate that the sex difference in LHRH responsiveness may be attributed to the stimulatory effect of 17 beta-estradiol and the inhibitory effect of testosterone on the LH cells.
Production of alanine and glutamine by atrial muscle from fed and fasted rats
Authors: Tischler M. E. , Goldberg A. L.
Published: December 2017

During incubation in vitro, rat atrial and rabbit papillary muscles synthesized and released large amounts of alanine and even higher amounts of glutamine. The amino groups used in the synthesis of alanine and glutamine appeared to be derived from the catabolism of other amino acids, specifically, leucine, isoleucine, valine, aspartate, glutamate, asparagine, arginine, and proline. The total amount of glutamine and alanine synthesized increased by 45% in atrial muscle from fasted rats, in which the oxidation of branched-chain amino acids is enhanced. In atria from fed rats, addition of leucine stimulated by about 20% the production of both alanine and glutamine, probably by providing additional amino groups for transamination with alpha-ketoglutarate. However, in cardiac muscle from fasted rats and rabbits, leucine increased the production of glutamine, but not of alanine. Isoleucine and valine, by contrast, enhanced production of both alanine and glutamine in these tissues. In the presence of leucine, low levels of pyruvate seem to limit the production of alanine, apparently because leucine, unlike isoleucine or valine, promotes the conversion of pyruvate to lactate.
Insulin regulation of skeletal muscle glycogen metabolism
Authors: Chiasson J. L. , Dietz M. R. , Shikama H. , Wootten M. , Exton J. H.
Published: December 2017

Using the perfused rat hindlimb preparation, the role of insulin in the regulation of glycogen metabolism in voluntary skeletal muscle has been characterized. A maximally effective concentration of insulin (1 mU/ml) caused a threefold increase in glucose clearance by 5 min. However, the -glucose-6-P/+glucose-6-P activity ratio of glycogen synthase was not significantly increased before 20 min. Insulin concentrations as low as 0.1 mU/ml significantly modified the glycogen synthase activity ratio and the half-maximal activation constant (A0.5) for glucose-6-P at 30 min, but had no effect on tissue cAMP. These changes were not dependent on the presence of glucose and were not modified by fasting. These results indicate that high physiological concentrations of insulin activate glycogen synthase in voluntary skeletal muscle and that this effect is independent of changes in glucose uptake or tissue cyclic AMP.
Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D
Authors: Trechsel U. , Eisman J. A. , Fischer J. A. , Bonjour J. P. , Fleisch H.
Published: December 2017

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.
Potassium ion as a regulator of adrenal angiotensin II receptors
Authors: Douglas J. G.
Published: December 2017

The importance of potassium as a regulator of angiotensin II receptors of two target tissues has been investigated by combining high-K+ diet in rats with a converting enzyme inhibitor (Captopril; SQ 14,225) or angiotensin II. K+ loading alone produced the characteristic increase in Ka and decrease in number of smooth muscle receptors and decrease in Ka and increase in number of adrenal receptors. The combination of Captopril and high-K+ diet blocked the development of most of these effects. In smooth muscle, the number of angiotensin II receptors was 40% higher (n = 5) and Ka was 94% lower (n = 5); in the adrenal the Ka was 29% higher (n = 4) than with K+ loading alone. However, development of the increment in number of adrenal receptors occurred in spite of Captopril treatment. In addition, angiotensin II infusion concomitantly with high-K+ diet resulted in a further increment in the number of adrenal receptors. These studies represent the first example of an ion as a regulator of a peptide hormone receptor and emphasize that different mechanisms of regulation are involved in adrenal and smooth muscle.
Polyamine metabolism during cardiac hypertrophy
Authors: Pegg A. E. , Hibasami H.
Published: December 2017

Treatment with thyroxine for 7 days to produce myocardial hypertrophy led to an increase in the content of putrescine, spermidine, and spermine in the rat heart. The content of decarboxylated S-adenosylmethionine, the source of the aminopropyl groups needed for polyamine synthesis, was increased by the thyroxine treatment as were the activities of ornithine and S-adenosylmethionine decarboxylases. The enhanced S-adenosylmethionine decarboxylase activity measured in vitro was due to an increase in the amount of enzyme protein as measured by immunotitration with a specific antiserum. In vivo, decarboxylation of S-adenosylmethionine was, therefore, increased both by the increased amount of enzyme protein and by the elevated concentration of putrescine (which activates the enzyme) brought about by the enhanced ornithine carboxylase activity. Spermine synthase did not change significantly during the treatment and spermidine synthase increased only slightly. Therefore, the accumulation of polyamines was mediated predominantly via the increased availability of both putrescine and decarboxylated S-adenosylmethionine. Administration of 1,3-diamino-2-propanol led to a rapid reduction in the activity of ornithine decarboxylase in the heart, and continued exposure to this substance by its inclusion in the drinking water completely prevented the increase in concentration of putrescine and polyamines in response to thyroxine. However, cardiac hypertrophy as measured by the increase in cardiac mass was not prevented by such treatment with 1,3-diaminopropanol, showing that the increased content of polyamines was not essential for the hypertrophic response.
Epitrochlearis muscle. I. Mechanical performance, energetics, and fiber composition
Authors: Nesher R. , Karl I. E. , Kaiser K. E. , Kipnis D. M.
Published: December 2017

An in vitro rat muscle preparation is described that can contract at rates of 12–240 twitches/min. Maximum dF/dt paralleled maximum twitch tension, their ratio being constant at approximately 8 ms for contraction rates of 12-120 twitches/min. Time to peak tension was 8–13 ms, time to peak dF/dt 5–8 ms, and half-relaxation time 4 ms. These parameters were unaffected by rate of contraction or duration of isometric work. Differential ATPase staining demonstrated that 60–65% of the fibers were fast-twitch white, 20% fast-twitch red, and 15% slow-twitch red. The preponderance of fast-twitch fibers correlated with the observed mechanical performance of the muscle. Muscles contracting for 60 min at rates up to 48 twitches/min maintained total adenine nucleotide content (ATP, ADP, AMP) at near resting levels. At higher twitch rates (72–240 twitches/min), total adenine nucleotide content decreased 40%, reflecting exclusively a fall in ATP in the presence of adequate phosphocreatine stores. Adequate oxygenation was reflected by lactate-to-pyruvate ratios in the range of 11–15 at all rates of contraction.
Serotoninergic system and circadian rhythms of ACTH and corticosterone in rats
Authors: Szafarczyk A. , Alonso G. , Ixart G. , Malaval F. , Nouguier-Soule J. , Assenmacher I.
Published: December 2017

The circadian rhythms of plasma ACTH and corticosterone and of locomotor activity were explored in chronically cannulated female rats, after elimination of serotoninergic (5HT) innervation of the SCN (suprachiasmatic nuclei) either by stereotaxic lesion of the median and dorsal midbrain raphe nuclei (RX) or by local injection of SCN with the neurotoxin 5,7-dihydroxytryptamine (5,7DHT). Completeness of 5HT denervation was checked on serial sections of the hypothalamus either by the Falk-Hillarp technique or by radioautography. Neither lesion eliminated the intrahypothalamic 5HT system, which, however does not take part in the 5HT innervation of the SCN. In both experimental series, the circadian rhythms of the three parameters investigated were maintained in unchanged phase relationships compared to the sham-lesioned controls, and with respect to the photoperiod (12 light-12 dark). However, the estimated amplitudes of the ACTH rhythms dropped by 43% (RX) to 47% (5,7DHT) and their mean levels by 44% (RX) to 60% (5,7DHT), whereas the corticosterone rhythm displayed normal amplitude and its mean level rose by 24% (RX) or 38% (5,7DHT). In regard to locomotor activity rhythm, the most noticeable alteration was a 25–55% increase in the light-phase activity of both experimental groups with a correlative increase in the L/D activity ratio. The essential role of 5HT innervation of the SCN therefore seems to be to facilitate circadian control of the ACTH rhythm.
Neural influences on oscillations in basal plasma levels of insulin in monkeys
Authors: Hansen B. C. , Pek S. , Koerker D. J. , Goodner C. J. , Wolfe R. A. , Schielke G. P.
Published: December 2017

The effects of cholinergic and adrenergic blocking agents on the period and amplitude of sustained oscillations in plasma levels of insulin and glucose were studied in 16 overnight-fasted conscious rhesus monkeys. Blood samples were withdrawn at 2-min intervals before and during or following administration of drugs that affect neurotransmission. Cholinergic blockade with atropine had no effect on the oscillations. alpha-Adrenergic blockade with phentolamine caused a rise in plasma insulin that lasted less than 10 min and was followed by a slight, although not consistent, decrease in mean insulin and a consistent small decrease in glucose. There was a sustained increase in heart rate, but no effect on the oscillations of insulin or glucose. beta-Adrenergic blockade induced by propranolol led to persistent decreases in mean plasma insulin 60% below the base line, small but variable decreases in glucose, and a sustained decrease in heart rate, but no change in period or relative amplitude of the oscillations in plasma levels of either insulin or glucose. General anesthesia with pentobarbital did not eliminate these oscillations. Our observations on the failure of the blockade of certain putative efferent pathways or depression of higher cortical centers to alter the period of the oscillations of insulin reduce the likelihood that the oscillations are transmitted from a pacemaker in the central nervous system.
Modified assays to detect activation of glycogen synthase following exercise
Authors: Kochan R. G. , Lamb D. R. , Reimann E. M. , Schlender K. K.
Published: December 2017

Glycogen levels and glycogen synthase activity were measured in red vastus lateralis muscle of male Sprague-Dawley rats killed at rest, immediately after swimming to exhaustion, or 4 h postexhaustion. Glycogen levels were very low immediately after the exercise but returned to preexercise levels after 4 h of recovery. Activation of glycogen synthase by glucose 6-phosphate (G6P) was determined in the standard assay of Thomas et al. (Anal. Biochem. 25: 486-499, 1968) using 4.4 mM uridine diphosphate glucose (UDPG) (pH 7.8) or in a modified assay using 0.03 mM UDPG (pH 6.9) in the absence or presence of inhibitor (inorganic phosphate or uridine 5'-diphosphate). Activation of glycogen synthase was determined by measuring activity ratio (activity in the absence of G6P divided by activity in the presence of G6P), A0.5 for G6P (concentration of G6P producing half-maximal activation), and fractional velocity (activity with low G6P divided by activity with high G6P). All three measurements indicated glycogen synthase was significantly activated immediately after exhaustion. Activation after 4 h of recovery was not detected using activity ratio but was readily apparent when fractional velocity of A0.5 for G6P were measured.
Protein degradation and synthesis during recovery from myocardial ischemia
Authors: Williams E. H. , Kao R. L. , Morgan H. E.
Published: December 2017

Rates of synthesis and degradation of heart protein were measured during 30 or 60 min of myocardial ischemia and during the 30 or 60 min following these ischemic periods. During ischemia, rates of protein synthesis and degradation were reduced. Resumption of control rates of coronary flow after 30 min of ischemia resulted in complete restoration of creatine phosphate and partial recovery of ATP (75%), developed pressure (79%), and cardiac output (80%). After 60 min of ischemia, restoration of flow completely restored creatine phosphate but resulted in poor recovery of ATP (57%), developed pressure (26%), and cardiac output (63%). During the recovery phase, rates of protein synthesis and degradation of protein to free amino acids were the same as in hearts that had been perfused for a comparable period as working aerobic preparations. These findings were consistent with inhibition of an initial step in proteolysis during the period of ischemia followed by return to control rates of degradation when oxygen delivery and energy levels were restored.
Effects of indomethacin on plasma renin activity in the conscious rat
Authors: Suzuki S. , Franco-Saenz R. , Tan S. Y. , Mulrow P. J.
Published: December 2017

The role of prostaglandins in the control of renin release in vivo was evaluated in the conscious rat. Indomethacin suppressed urinary prostaglandin E2 (PGE2) excretion from 5.3 +/- 0.5 to 2.6 +/- 0.5 ng/3 h (P less than 0.001). Basal plasma renin activity (PRA) fell from 6.20 +/- 1.07 to 2.98 +/- 0.45 ng . ml-1 . h-1 (P less than 0.02). Indomethacin suppressed PRA stimulated by furosemide, insulin-induced hypoglycemia, hydralazine, isoproterenol, arachidonic acid, and sodium-free diet, whereas PRA stimulated by PGE2 was not suppressed by indomethacin. The suppression of PRA by indomethacin in the sodium-deplete state rules out sodium retention as the mechanism of action of indomethacin. These results indicate that inhibition of prostaglandin synthesis by indomethacin partially blocks the renin response to several of the known stimulators, suggesting that prostaglandins may play a pivotal role in the control of renin release.
Voltage dependence of rhythmic plateau potentials of pancreatic islet cells
Authors: Cook D. L. , Porte D. , Crill W. E.
Published: December 2017

The origin and control of glucose-induced rhythmic plateau potentials of pancreatic islet cells have been studied with intracellular microelectrodes in isolated mouse islets. Rapid changes of extracellular potassium concentration and direct electrical stimulation via a suction electrode were used to perturb islet cell membrane potentials. We show that brief depolarizing stimuli trigger permature plateau potentials, and brief hyperpolarizing currents abort endogenous plateaus. Both responses occur in an all-or-none manner, show a reciprocal relationship between stimulus strength and stimulus duration, have stimulus thresholds that approach zero at the time of the endogenous event, and completely reset the endogenous plateau rhythm. These results indicate that the plateau potentials are due to voltage-dependent regenerative mechanisms as in other electrically excitable tissues and implicate membrane potential or membrane ionic fluxes in the glucose-dependent pacemaker system that triggers their onset and offset.
Regulation of guinea pig heart phosphorylase kinase by cAMP, protein kinase, and calcium
Authors: Hayes J. S. , Mayer S. E.
Published: December 2017

In skeletal muscle the activation of phosphorylase kinase (PK) associated with phosphorylation of the enzyme can be measured as an increase in the pH 6.8:8.2 activity ratio. Phosphorylation leads to a 20- to 30-fold increase in PK activity (PKA) at pH 6.8 and a large decrease in the Km for phosphorylase. Perfused guinea pig hearts exposed to isoproterenol (0.3 microM) showed an increase in PKA, but without an increase in the pH 6.8:8.2 activity ratio. In a 10-fold dilution of guinea pig heart cytosol exposed to cAMP + methylisobutylxanthine, PKA was stimulated twofold at pH 7.5. Addition of exogenous protein kinase stimulated PKA fourfold. Both methods of activation were reversible and were blocked by the heat-stable inhibitor of protein kinase. Guinea pig heart PK was Ca2+-dependent requiring 0.6 microM Ca2+ for half-maximal activity. Kinetic studies indicate that the Km of guinea pig heart PK for phosphorylase b at pH 6.8 is not markedly reduced after in vitro activation (35%). This could explain the observed lack of increase in the pH 6.8:8.2 activity ratio after exposure of hearts to isoproterenol. The time course for the activation of inotropic state and the glycogenolytic pathway in perfused guinea pig hearts by isoproterenol showed that these processes were maximally activated within 25 s. However, PK remained activated for 2 min, long after the other biochemical and physiological parameters had returned to control values. These data suggest that Ca2+, not phosphorylation state, is important in regulating the return of dP/dt to control levels after beta-adrenergic stimulation.