bluuebunny/crossref_metadata_2025 huggingface dataset:
Pedunculated polyp of the ileum protruding from a large diverticulum
Authors: Iwaya Yugo , Rowsell Corwyn , Grantcharov Teodor , Marcon Norman E
Published: December 2017

Introduction

A 52-year-old woman presented with iron deficiency anaemia and postprandial right lower quadrant pain. Abdominal examination was unremarkable and laboratory results showed mild anaemia (haemoglobin 11.3 g/dL). Upper and lower endoscopies did not reveal any source of bleeding. Video capsule endoscopy was performed which showed a large polypoid lesion in the mid-ileum (figure 1). Abdominal contrast enhanced CT demonstrated a heterogeneously enhancing pedunculated polyp measuring approximately 6 cm (figure 2). Retrograde double-balloon enteroscopy was performed which revealed a large pedunculated polyp with hyperplastic-like mucosa protruding from a large diverticulum located approximately 70 cm proximal to the ileocaecal valve (figure 3A). The stalk appeared to arise from the base of the diverticulum (figure 3B). A technetium-99m pertechnetate scintigraphy revealed no ectopic gastric mucosa.

Figure 1

Video capsule endoscopy shows a large polypoid lesion.

Figure 2

CT shows a heterogeneously enhancing pedunculated polyp (arrow).

Figure 3

Retrograde double-balloon enteroscopy images. (A) Large pedunculated polyp protruding from a large diverticulum. (B) The stalk appears to arise from the base of the diverticulum.

Question

What is the diagnosis?
Marijuana use and fecundability in a North American preconception cohort study
Authors: Wise Lauren A , Wesselink Amelia K , Hatch Elizabeth E , Rothman Kenneth J , Mikkelsen Ellen M , Sørensen Henrik Toft , Mahalingaiah Shruthi
Published: December 2017

Background

The influence of marijuana use on human fertility has not been well studied. We evaluated the association between female and male use of marijuana and fecundability in Pregnancy Study Online, a prospective cohort of North American couples.

Methods

Female participants completed a baseline questionnaire on which they reported lifestyle and behavioural factors, including frequency of marijuana use within the previous 2 months. Male partners completed an optional baseline questionnaire on similar factors, including marijuana use. Women completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, initiation of fertility treatment or loss to follow-up, whichever came first. The analysis was restricted to 4194 women (1125 couples) with ≤6 cycles of pregnancy attempt time at study enrolment (2013–2017). Fecundability ratios (FR) and 95% CIs were estimated using proportional probabilities regression models, with adjustment for potential confounders.

Results

Men (14.2%) were more likely than women (11.6%) to be marijuana users. FRs for female marijuana use <1 and ≥1 time/week relative to non-use were 0.99 (95% CI 0.85 to 1.16) and 0.98 (95% CI 0.80 to 1.20), respectively. FRs for male marijuana use <1 and ≥1 time/week relative to non-use were 0.87 (95% CI 0.66 to 1.15) and 1.24 (95% CI 0.90 to 1.70), respectively. Associations for frequent marijuana use (≥1 time/week) were attenuated among non-smoking men (FR=1.21, 95% CI 0.84 to 1.74), but stronger among men reporting intercourse ≥4 times/week (FR=1.35, 95% CI 0.72 to 2.53).

Conclusions

In this preconception cohort study, there was little overall association between female or male marijuana use and fecundability.
Do flexible work policies improve parents’ health? A natural experiment based on the UK Millennium Cohort Study
Authors: Avendano Mauricio , Panico Lidia
Published: December 2017

Background

There is limited evidence of the impact of policies to promote work–family balance on family health. Exploiting the introduction of the UK Flexible Working Act (2003), we examined whether a policy that grants parentsthe right to requestflexible work influences their health and well-being.

Methods

Using the UK Millennium Cohort Study, we focus on 6424 mothers employed in 2001–2002, when the cohort child was 9 months old, until their child’s seventh birthday. We used a difference-in-differences (DiD) approach to compare changes in outcomes before and after the policy among mothers most likely to benefit and mothers unlikely to benefit from the policy.

Results

Flexible working increased in a small group of mothers (n=548) whose employer did not offer work flexibility before the reform (treatment group). By contrast, among mothers whose employer already offered flexible work before the reform (control group, n=5810), there was little change or a slight decline in flexible working. DiD estimates suggest that the policy was associated with an increase in flexible working (37.5 percentage points, 95% CI 32.9 to 41.6), but it had no impact on self-rated health (−1.6 percentage points, 95% CI −4.4 to 1.1), long-term illness (−1.87 percentage points, 95% CI −4.3 to 0.5) or life satisfaction scores (β=0.04, 95% CI −0.08 to 0.16).

Conclusion

The Flexible Working Act increased flexible working only among a small group of mothers who had not yet the right to request work flexibility, but it had no impact on their health and well-being. Policies promoting work flexibility may require stronger incentives for both parents and employers.
Neuropsychological outcome after subtemporal versus transsylvian approach for selective amygdalohippocampectomy in patients with mesial temporal lobe epilepsy: a randomised prospective clinical trial
Authors: Vogt Viola Lara , Delev Daniel , Grote Alexander , Schramm Johannes , von Lehe Marec , Elger Christian Erich , Witt Juri-Alexander , Helmstaedter Christoph
Published: December 2017

Objective

To compare the effects of different surgical approaches for selective amygdalohippocampectomy in patients with pharmacoresistant mesial temporal lobe epilepsy with regard to the neuropsychological outcome and to replicate an earlier study employing a matched-pair design.

Method

47 patients were randomised to subtemporal versus transsylvian approaches. Memory, language, attentional and executive functions were assessed before and 1 year after surgery. Multivariate analyses of variance (MANOVAs) with presurgical and postsurgical assessments as within-subject variables and approach and side of surgery as between-subject factors were calculated. Additionally, the frequencies of individual performance changes based on reliable change indices were analysed.

Results

Seizure freedom International League Against Epilepsy (ILAE) 1a, was achieved in 62% of all patients without group difference. MANOVAs revealed no significant effects of approach on cognition. Tested separately for each parameter, verbal recognition memory declined irrespective of approach. Post hoc tests revealed that on group level, the subtemporal approach was associated with a worse outcome for verbal learning and delayed free recall as well as for semantic fluency. Accordingly, on individual level, more patients in the subtemporal group declined in verbal learning. Left side of surgery was associated with decline in naming regardless of approach.

Conclusion

The main analysis did not confirm the effects of approach on memory outcome seen in our previous study. Post hoc testing, however, showed greater memory losses with the subtemporal approach. Previous findings were replicated for semantic fluency. The discrepant results are discussed on the background of the different study designs.
Launching problem space research in the frenzy of software production
Authors: Young Indi , Mangalam Kunyi
Published: December 2017

This forum is dedicated to maximizing the success of HCI practitioners within the frenetic world of product and service design. It focuses on UX strategy approaches, leadership, management techniques, and above all the challenge of bringing HCI to peer-level status with longstanding business disciplines such as marketing and engineering.
---Daniel Rosenberg, Editor
Rethinking assumptions in the design of health and wellness tracking tools
Authors: Munson Sean A.
Published: December 2017

This forum is dedicated to personal health in all its many facets: decision-making, goal setting, celebration, discovery, reflection, and coordination, among others. We look at innovations in interactive technologies and how they help address current critical healthcare challenges.
--Yunan Chen, Editor
Characterization of mitochondrial-uncoupling protein in bovine fetus and newborn calf
Authors: Casteilla L. , Forest C. , Robelin J. , Ricquier D. , Lombet A. , Ailhaud G.
Published: December 2017

Development changes in the content of the mitochondrial-uncoupling protein (UCP) have been studied in adipose depots of bovine fetuses and a newborn calf as well as in adipose depots of newborn and aging lambs. The occurrence of UCP unique to brown adipose tissue (BAT) was investigated by GDP binding, photoaffinity labeling with 8-azidoadenosine 5'-triphosphate, and immunoblots using specific antibodies directed against rat UCP. A protein of 32,000 relative molecular weight was characterized in both species with properties similar to those of rodent UCP. In bovine, UCP became detectable in the perirenal adipose tissue at day -80 and its content increased until birth. Both in bovine (perirenal, subscapular, and retroperitoneal sites) and in ovine (perirenal, subscapular, retroperitoneal, and pericardiac sites), all adipose tissues except the subcutaneous adipose tissue contained at birth UCP and thus can be considered as BAT. The data indicate that the perirenal adipose depot should play in bovine and ovine a major thermogenic role at birth, whereas perirenal and pericardiac adipose tissues of lambs held under cold conditions for 45 days after birth did not show any immunoreactive UCP.
Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels
Authors: Hingorani V. , Brecher P.
Published: December 2017

Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6-14C]glucose or [1-14C]oleic acid and the incorporation of radioactivity into 14CO2, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14CO2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.
Altered hepatic vasopressin and alpha 1-adrenergic receptors after chronic endotoxin infusion
Authors: Roth B. L. , Spitzer J. A.
Published: December 2017

Sepsis and septic shock are complicated by a number of hemodynamic and metabolic aberrations. These include catecholamine refractoriness and altered glucose metabolism. Recently, a nonshock rat model of continuous endotoxin infusion via an implanted osmotic pump was developed that reproduces some of the metabolic and cardiovascular findings of human sepsis. By using this model, we have found a decreased number of hepatic plasma membrane alpha 1-adrenergic and [Arg8]vasopressin receptors in rats continuously infused with endotoxin. There was a significant decrease in [3H]prazosin (35 +/- 7%) and [3H] [Arg8]vasopressin (43 +/- 8%) receptors after 30 h of continuous endotoxin infusion with no change in affinity. The ability of norepinephrine to form the high-affinity complex with alpha 1-adrenergic receptors was not altered after chronic endotoxin infusion. The results are consistent with the concept that alterations in receptor number might underlie certain of the metabolic consequences of chronic sepsis.
A decline in myocardial and hepatic norepinephrine turnover with age in Fischer 344 rats
Authors: Mazzeo R. S. , Horvath S. M.
Published: December 2017

The purpose of the present study was to determine any age-related alterations in norepinephrine (NE) turnover rate in various tissues of the Fischer 344 rats. Female rats ages 3, 12, and 22 mo were given an intraperitoneal injection of alpha-methyl-p-tyrosine, a known inhibitor of tyrosine hydroxylase. NE turnover was determined mathematically by monitoring the exponential decline of tissues levels over 7 h. Cardiac NE turnover rates averaged 38.4, 31.4, and 25.2 ng X g-1 X h-1 for the 3-, 12-, and 22-mo-old age groups, respectively. A similar trend was found for the liver NE turnover rates (12.9, 9.2, and 6.8 ng X g-1 X h-1 for 3-, 12-, and 22-mo-old groups, respectively). It was concluded that the reduced catecholamine content seen in various tissues with advancing age can be explained, in part, by a diminished ability for catecholamine synthesis.
Stimulation of dog gastropancreatic hormone release by neuromedin B and its analogues
Authors: Mukai H. , Kawai K. , Suzuki Y. , Yamashita K. , Munekata E.
Published: December 2017

The effects on gastrin, insulin, and glucagon release of neuromedin B (NMB), the C-fragment decapeptide of gastrin-releasing peptide-10 (GRP-10), seven analogues replacing amino acid positions 3, 6, and 9, and two C-terminal desamide analogues were examined in conscious dogs using intravenous bolus injection of these peptides study the structure-activity relationship of two bombesin-related peptides identified in mammals. The replacement from valine of position 6 of GRP-10 to threonine effectively reduced the stimulatory potency of these hormone secretions. Removal of the C-terminal amide of NMB and GRP-10 resulted in an almost complete loss of their stimulatory effect on gastrin secretion. [Leu3]GRP-10 elicited the most potent stimulatory activity on three hormone secretions among the analogues including NMB and GRP-10. These results indicate that valine in position 6 of GRP-10 and C-terminal amide of two peptides play an important role in the bioactivities of bombesin family peptides.
Spare receptors, partial agonists, and ternary complex model of drug action
Authors: Homer L. D. , Nielsen T. B.
Published: December 2017

The occurrence of spare receptors and partial agonists for smooth muscle contractions mediated by alpha 1-adrenergic receptors can be accounted for with a ternary complex model of drug action presented here. In this model, receptor-ligand complexes are assumed to be inactive until the complex binds to an activating protein. Contractile responses are assumed to be proportional to the concentration of ternary complex (receptor-ligand-activator) regardless of the ligand involved. Antagonists are unable to form the ternary complex. Spare receptors are present as the inactive receptor-ligand complex. Such a model is shown to fit already published data on membrane binding of alpha 1-adrenergic agonists as well as contractile responses to the agonist. Schild plots are expected to resemble those of a single-site model of drug action. The double-reciprocal plots of receptor-inactivation studies will display only a slight curvature as may be seen in previously published articles. Partial agonists may have 50% response doses lowe or higher than full agonists. The hypothesis that ternary complexes are formed with alpha 1-receptors could be tested more critically with receptor-inactivation studies using both antagonists and agonists. Partial inactivation of receptor and activator protein should reduce the binding of antagonist without altering the concentration needed to bind to 50% of the receptors. On the other hand, the concentration of agonist required to displace 50% of a bound antagonist is expected to increase. The proposal that contractile responses are proportional to the ternary complex concentration could be tested by fitting the ternary complex model to the data from studies of contractions induced by partial agonists as well as full agonists.
Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells
Authors: Yamashita N. , Kojima I. , Shibuya N. , Ogata E.
Published: December 2017

The effect of pertussis toxin on somatostatin-induced K+ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K+ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma 1, 0/10 in adenoma 2). Spontaneous action potentials, K+, Na+, and Ca2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [32P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.
Beta-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women
Authors: Vernet O. , Nacht C. A. , Christin L. , Schutz Y. , Danforth E. , Jequier E.
Published: December 2017

Continuous respiratory exchange measurements were performed in nine obese and eight lean women for 1 h before, 3 h during, and 1 h after the intravenous administration of a nutrient mixture infused at twice the postabsorptive resting energy expenditure (REE). This experiment was conducted without or with beta-adrenergic blockade (iv propranolol). Propranolol administration did not change the postabsorptive REE [i.e., 1.03 +/- 0.07 before vs. 1.01 +/- 0.02 kcal/min after administration in lean women and 1.16 +/- 0.04 vs. 1.15 +/- 0.03 kcal/min (NS) in obese women]. The mean overall thermogenic response expressed as a percentage of the infused energy was similar in both groups and was not significantly blunted after propranolol infusion [6.9 +/- 0.4 vs. 5.9 +/- 0.6% in the lean women and 7.5 +/- 0.5 vs. 7.1 +/- 0.6% (NS) in the obese women]. During beta-adrenergic blockade the rate of lipid oxidation decreased in the lean group but was unchanged in the obese group and the glycemic response to nutrient administration was significantly higher in both groups than without propranolol. It is concluded that beta-adrenergic blockade has no effect on REE and on intravenous nutrient-induced thermogenesis in both lean and obese women.
Sarcolemmal Ca2+ transport in streptozotocin-induced diabetic cardiomyopathy in rats
Authors: Makino N. , Dhalla K. S. , Elimban V. , Dhalla N. S.
Published: December 2017

Heart sarcolemmal membranes were isolated by the sucrose density gradient method from rats with chronic diabetes induced by a streptozotocin (65 mg/kg iv) injection. Na+-dependent Ca2+-uptake activities were significantly depressed in diabetic sarcolemmal membranes; such alterations were evident at different incubation times and at different concentrations of Ca2+. Administration of insulin to diabetic rats normalized the Na+-dependent Ca2+-uptake activities. ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent ATPase, which represents Ca2+-pump mechanisms, were significantly depressed in sarcolemmal preparations for diabetic rats and these changes were also reversible upon insulin treatment. An increase in lysophosphatidylcholine and a decrease in phosphatidylethanolamine as well as diphosphatidylglycerol contents were observed in heart membranes isolated from diabetic rats but other phospholipids were unchanged. Cholesterol-to-phospholipid ratio was significantly increased in preparations from diabetic rats. These results indicate a depression in the ability of the cell to remove Ca2+ through Na+-Ca2+ exchange and Ca2+-pump mechanisms in sarcolemma, and these defects may contribute to the occurrence of intracellular Ca2+ overload and diabetic cardiomyopathy.
A microdialysis method allowing characterization of intercellular water space in humans
Authors: Lonnroth P. , Jansson P. A. , Smith U.
Published: December 2017

To evaluate the usefulness of the tissue-microdialysis technique in humans, the glucose concentration in the intercellular water space was measured in the abdominal subcutaneous region in healthy subjects. A 30 X 0.3 mm dialysis fiber with a 3,000 MW cutoff was used. The dialysis catheter was calibrated in vivo by perfusing it with isotonic saline and four to five different glucose concentrations (0-5 mM). The perfusate was collected in 6-min fractions. Regression analysis of the results of the calibration yielded the perfusate glucose concentration, which was in equilibrium with the surrounding tissue. Validation experiments showed that this value could be precisely measured and represented the intercellular glucose concentration. The recovery of glucose in the dialysate (dialysate glucose concentration/medium) during the calibrations in vivo was only approximately one-half of that in vitro (recovery factors 0.28 vs. 0.44, respectively). Under steady-state conditions, the intercellular glucose concentration was similar to the glucose levels in the cubital vein. It is concluded that this microdialysis technique is a useful tool allowing measurements of metabolically active substances in the intercellular water space in vivo provided that the calibrations are properly performed.
Effects of food restriction on lactate production from glucose by rat adipocytes
Authors: Thacker S. V. , Nickel M. , DiGirolamo M.
Published: December 2017

We investigated the effects of acute food deprivation on the rates of glucose metabolism and lactate production by epididymal fat cells isolated from 2- and 8-mo-old Wistar rats in one of three nutritional states: fed ad libitum, restricted to 50% of ad libitum, or fasted for 48 h. Food restriction did not affect total rates of basal glucose metabolism but significantly altered its pattern. In small fat cells from 2-mo-old rats, donor's food restriction led to decreased basal and insulin-stimulated glucose oxidation and fatty acid synthesis but led to increased lactate production, which increased from 4% of total glucose metabolized by cells from fed rats to 62% by cells from fasted rats. In large fat cells from 8-mo-old rats, donor's food restriction produced minimal changes in basal glucose metabolism and lactate production (already elevated at 37% of total) but caused insulin-stimulated lactate production to increase. These findings indicate that adipose tissue can produce significant amounts of lactate (with adipocyte enlargement and/or food deprivation) and may play an important role in extrahepatic generation of triose intermediates and in the Cori cycle.
Sympathetic activity in brown adipose tissue in lactating mice
Authors: Trayhurn P. , Wusteman M. C.
Published: December 2017

Sympathetic activity has been assessed, by measurements of norepinephrine turnover, in interscapular brown adipose tissue of mice during lactation. Norepinephrine turnover was reduced in brown adipose tissue from early lactation until weaning. The reduction in turnover occurred in dams suckling either large-or small-sized litters. Norepinephrine turnover returned to the control level after natural weaning and increased rapidly after abrupt weaning at peak lactation. Acute exposure to cold resulted in a large increase in norepinephrine turnover in brown adipose tissue of lactating mice, as in control animals. These results indicate that sympathetic activity is suppressed in brown adipose tissue during lactation, but sympathetic responsiveness is retained. The reduction in sympathetic activity is likely to be responsible for the decrease in brown adipose tissue thermogenesis in lactation. Norepinephrine turnover in the heart tended to be reduced at peak lactation, suggesting that there may be a general decrease in sympathetic activity in the lactating animal. In contrast to the normal animal, the hyperphagia of lactation does not lead to an activation of the sympathetic nervous system.
Leucine metabolism in perfused rat skeletal muscle during contractions
Authors: Hood D. A. , Terjung R. L.
Published: December 2017

An isolated single rat hindlimb muscle preparation was used to examine leucine metabolism during steady-state conditions as a function of metabolic rate (VO2) and leucine concentration. The rates of muscle leucine uptake and leucine oxidation (measured as alpha-decarboxylation) were dependent on leucine delivery. At a physiological leucine concentration (0.1 mM), leucine uptake and alpha-ketoisocaproic acid (KIC) release during rest was 12.8 +/- 0.4 and 1.86 +/- 0.06 nmol.min-1.g-1 g, respectively. Leucine oxidation was 2.35 +/- 0.11 nmol.min-1.g-1 (n = 24) and if fully oxidized could account for only 3-4% of the resting VO2. This fraction was reduced to approximately 1% during contractions. The rate of leucine oxidation progressively increased, up to two to three times above rest (6-7 nmol.min-1.g-1), during contractions of graded frequency (7.5, 15, 30, 45, and 60 tetani/min) in a manner related to the eightfold increase in VO2 of the mixed fiber muscle. The fraction of muscle leucine uptake that was transaminated (i.e., leucine decarboxylation + KIC release) increased from 33% at rest to approximately 60% during contractions. The increase in leucine oxidation during contractions was probably primarily due to the high oxidative fast-twitch, red muscle mass, whose VO2 was estimated to increase up to 24-fold above rest. On the basis of our observed rates of muscle leucine alpha-decarboxylation, it is reasonable to attribute the rates of whole-body leucine oxidation of nontrained individuals during exercise to leucine oxidation by the working muscle.
Disappearance of growth hormone from plasma of fetal and newborn sheep
Authors: Power G. G. , Ball K. T. , Gluckman P. D.
Published: December 2017

The disappearance of growth hormone (GH) from plasma was measured after a single intravenous injection in fetal and newborn sheep and fetal sheep after simulated birth in utero. The process was adequately described when separated into two exponential components, consistent with an inner (plasma) and outer (composite tissue) pool. Plasma clearance rate increased from 3.4 +/- 0.2 (SE, n = 6) in fetuses to 3.9 +/- 0.1 (n = 5) ml.min-1.kg-1 in newborns (P less than 0.05), but was not altered significantly after simulated delivery in utero. The volume of distribution decreased from 74 +/- 4 ml/kg before birth to 47 +/- 2 ml after natural birth (P less than 0.001). The basal secretory rate decreased from 2.4 +/- 0.2 before birth to 0.27 +/- 0.02 microgram/min after birth (P less than 0.001) and to a lesser extent after simulated delivery. The rate constant for irreversible loss, Kd, increased from 0.052 +/- 0.004 min-1 before birth to 0.093 +/- 0.002 min-1 after birth (P less than 0.001). Because plasma GH concentration in steady state equals secretory rate/(volume of distribution X Kd), one may calculate that 83% of the total decrease in GH, which occurs after birth, can be explained by diminished secretory rate, whereas 17% can be explained by more rapid loss from the plasma.
Insulin resistance in uremia: insulin receptor kinase activity in liver and muscle from chronic uremic rats
Authors: Cecchin F. , Ittoop O. , Sinha M. K. , Caro J. F.
Published: December 2017

We have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the beta-subunit and insulin receptor kinase activity using Glu80, Tyr20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristic of the receptors, as determined by electrophoretic mobilities of affinity labeled alpha-subunit and the phosphorylated beta-subunit, were normal in uremia. 125I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus our data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase.
Characterization of beta-adrenergic receptors of human skeletal muscle obtained by needle biopsy
Authors: Liggett S. B. , Shah S. D. , Cryer P. E.
Published: December 2017

Human skeletal muscle beta-adrenergic receptors were characterized by 125I-iodopindolol radioligand-binding studies of homogenates prepared from small muscle samples obtained by percutaneous needle biopsy from the gastrocnemius of six normal subjects. Binding was saturable, reversible, and stereospecific, with typical kinetics and a rank-order potency characteristic of a beta-adrenergic receptor. In saturation-binding studies, the receptor density was 9.7 +/- 1.9 fmol/mg protein, with a dissociation constant of 24 +/- 2.2 pM. Competition studies with selective antagonists revealed a population of receptors exclusively of the beta 2-subtype. Basal and isoproterenol-stimulated adenylate cyclase activities were 79 +/- 22 and 150 +/- 60 pmol adenosine 3',5'-cyclic monophosphate.min-1.mg protein-1, respectively. These results support pharmacological observations of beta-adrenergic receptor-mediated cellular responses in mammalian skeletal muscle. By use of these methods, small quantities of skeletal muscle obtained in this manner can be used to study in vivo beta-adrenergic receptor regulatory phenomena in humans.
Regulation of corticotropin-releasing factor secretion in vitro by glucose
Authors: Widmaier E. P. , Plotsky P. M. , Sutton S. W. , Vale W. W.
Published: December 2017

The neurosecretory responses of the isolated rat hypothalamus were assessed in vitro. Rat hypothalamic blocks were incubated for 30 min in a N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered salt solution with 5.5 mM glucose (base-line collection period). The blocks were transferred to fresh buffer with a new concentration of glucose with or without various additions (test period); corticotropin-releasing factor (CRF) and other hormones in the media were determined by radioimmunoassay. CRF secretion was maximally increased to approximately 200% of base line at glucose concentrations less than 4 mM and decreased to 65% of base line at higher glucose concentrations. The increase in CRF secretion at low glucose (0.55 or 1.38 mM) was Ca2+ dependent and completely reversible. Hexamethonium, cyproheptadine, and atropine partially blocked the CRF response to 0.55 mM glucose. Glucose concentrations from 0 to 11 mM had no effect on the CRF response to 47.5 mM KCl. The inhibitory effects of high glucose were completely reversed by the addition of 2-deoxy-D-glucose (3-49 mM). Glucose levels did not alter secretion of either gonadotropin-releasing hormone or arginine vasopressin from hypothalamic blocks. The results suggest that the isolated rat hypothalamus is extremely sensitive to the level of glucose and that CRF is rapidly and reversibly secreted in response to slight reductions in glucose concentrations. These concentrations are consistent with those observed during moderate to severe hypoglycemia in vivo. The rise in glucocorticoids observed in vivo during hypoglycemia may result at least in part from the ability of the hypothalamus to directly sense glucose levels and promote secretion of CRF.
Triton WR-1339 injected into rats enters renal renin granules
Authors: Morris B. J.
Published: December 2017

To test directly the possibility that substances in extracellular fluid can gain access to renin storage granules in renal juxtaglomerular cells, rats were injected with Triton WR-1339, which binds to plasma proteins. A heavy granule fraction was prepared, and isopycnic sucrose density gradient centrifugation was performed. The renin granule peak was found to be altered from a mean equilibrium density of 1.202 g/ml in control rats to 1.196 g/ml for rats injected with Triton WR-1339 (P less than 0.005). The distribution of angiotensinogen, which is bound in kidney granules having a different buoyant density, was also examined and found to be unaltered. After injection, Triton WR-1339 binds to circulating plasma proteins. The results for renin support the possibility of pinocytotic uptake of protein-Triton WR-1339 complexes by the juxtaglomerular cells with subsequent fusion of the endocytotic lysosomal vacuoles with renin granules accounting for the translocation of ingested substances into the granule matrix. If so, the potential would therefore exist for interaction(s) of ingested extracellular substances with renin or other components in the granules. The present study has therefore demonstrated directly that endogenous extracellular substances may enter renin granules.
Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles
Authors: Max S. R. , Mill J. , Mearow K. , Konagaya M. , Konagaya Y. , Thomas J. W. , Banner C. , Vitkovic L.
Published: December 2017

The regulation of glutamine synthetase expression by dexamethasone was studied in rat skeletal muscles. Daily administration of dexamethasone caused striking enhancement of glutamine synthetase activity in plantaris, soleus, and diaphragm muscles. Northern blot analysis revealed that the dexamethasone-mediated increase of glutamine synthetase activity was associated with dramatically increased levels of glutamine synthetase mRNA. Both glutamine synthetase activity and mRNA levels were significantly elevated in plantaris muscle at 0.5 mg.kg-1.day-1 of dexamethasone, a dose that approximates endogenous corticosteroid levels in animals under severe stress. Quantification of changes in glutamine synthetase mRNA on the basis of total mRNA (by oligo dT hybridization) also revealed a major increase in glutamine synthetase mRNA. Dexamethasone was without effect on beta-tubulin mRNA levels, indicating that glutamine synthetase induction is not part of a global response to glucocorticoids. Dexamethasone treatment resulted in only an approximately 15% increase in glutamine synthetase activity in heart; there was no change in glutamine synthetase mRNA level in this tissue. Thus glucocorticoids regulate glutamine synthetase gene expression in rat skeletal muscles.
Effects of hypercalcemia and ouabain on plasma atrial natriuretic polypeptide in anesthetized dogs
Authors: Yamamoto A. , Shouji T. , Kimura S. , Aki Y. , Nakamura A. , Fukui K. , Iwao H. , Abe Y.
Published: December 2017

For the purpose of examining the role of calcium ion in the secretory process of atrial natriuretic polypeptide (ANP), we studied the effects of hypercalcemia and ouabain on plasma concentration of immunoreactive ANP (irANP). Pentobarbital sodium-anesthetized dogs were treated with calcium chloride infusion (0.136 mmol.kg-1.min-1, 10 min) or ouabain injection (30 micrograms/kg), and plasma irANP concentration, right atrial pressure, mean arterial pressure, heart rate, and serum calcium concentration were measured. To evaluate the effect of rising arterial pressure, plasma irANP concentration was also measured in dogs treated with phenylephrine hydrochloride (10 micrograms/kg). With calcium chloride infusion, serum calcium concentration and plasma irANP concentration, respectively, increased to about three times and about four times their basal levels. This increase of plasma irANP concentration was not attenuated by pretreatment with adrenoceptor blockers. Ouabain increased plasma irANP concentration to approximately 2.5 times the initial level. Neither calcium chloride nor ouabain produced any effect on right atrial pressure and heart rate, but both significantly increased mean atrial pressure. Phenylephrine caused a greater increase in mean arterial pressure than both calcium chloride and ouabain. However, there was no significant increase in plasma irANP concentration. These results suggest that the calcium ion may play a key role in the secretory process of ANP.
ANF inhibits glucose-stimulated insulin secretion in mouse and rat
Authors: Ahren B.
Published: December 2017

Atrial natriuretic factor (ANF) is synthesized in atrial cells and was recently demonstrated to also occur within islet glucagon cells. Therefore, we investigated the possible effects of synthetic rat ANF-(1-28) on basal and stimulated insulin and glucagon secretion in the mouse and on glucose-induced insulin secretion in the rat. We found that ANF did not affect basal levels of insulin, glucagon, or glucose when injected intravenously at dose levels between 0.25 and 4.0 nmol/kg in mice. However, when injected together with glucose (2.8 mmol/kg), ANF (4.0 nmol/kg) inhibited the increase in plasma insulin levels by 40%, from 114 +/- 8 microU/ml in controls to 81 +/- 8 microU/ml (P less than 0.01). Likewise, the increase in plasma insulin levels during an intravenous infusion of glucose in rats (10 mg/min) was significantly reduced by ANF (100 pmol.kg-1.min-1; P less than 0.001). In contrast, the increase in plasma levels of insulin and glucagon after the intravenous injection of the cholinergic agonist carbachol in mice (0.16 mumol/kg) was not significantly affected by ANF. We conclude that ANF inhibits glucose-stimulated insulin secretion in the mouse and the rat. The peptide may therefore be a modulator of insulin secretion.
Differential effects of electrolytic and chemical hypothalamic lesions on LH pulses in rats
Authors: Sisk C. L. , Nunez A. A. , Thebert M. M.
Published: December 2017

Electrolytic lesions of the arcuate nucleus were made in anesthetized adult castrated male rats. Luteinizing hormone (LH) pulse frequency averaged 2.4 pulses/h in controls but declined to a mean of 0.5 pulses/h in rats with bilateral damage to the arcuate nucleus. Because these lesions also damaged the median eminence, we tested the possibility that this disruption of LH secretion was due to coincidental damage to fibers of passage projecting to median eminence. Axon-sparing chemical lesions of the arcuate nucleus were made by intracranial injections of N-methyl-DL-aspartate (NMA) in anesthetized adult castrated rats. Mean LH pulse frequency was 2.3 and 2.5 pulses/h in control and NMA-injected rats, respectively. NMA injections destroyed arcuate neuronal cell bodies and produced a proliferation of glial cells within the nucleus. There was no apparent difference in the immunocytochemical staining intensity and distribution of luteinizing hormone-releasing hormone (LHRH) fibers in median eminence in rats receiving NMA or sham injections. These results suggest that the disruptive effects of electrolytic lesions of the arcuate nucleus on pulsatile LH secretion are a result of coincidental damage to LHRH neuronal projections to the median eminence and that neuronal cell bodies within the arcuate nucleus are not necessary for normal pulsatile LH secretion in male rats.
Effects of thyroid hormone on Na+-K+ transport in resting and stimulated rat skeletal muscle
Authors: Everts M. E. , Clausen T.
Published: December 2017

The effects of hypothyroidism and 3,5,3'-triiodothyronine (T3) treatment on passive Na+-K+ fluxes and Na+-K+ pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T3 (20 micrograms/100 g body wt), K+ efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na+ influx but no significant increase in [3H]ouabain binding site concentration. After 3 days of T3 treatment, the stimulating effect on K+ efflux and Na+ influx in soleus reached a plateau approximately 80 and 40% above control levels, respectively, whereas the maximum increase in [3H]ouabain binding site concentration (103%) was only fully developed after 8 days. Hypothyroidism decreased 86Rb efflux by 30%. The efflux of K+ and the influx of Na+ per contraction (both approximately 7 nmol/g wet wt) as well as the net loss of K+ induced by electrical stimulation were unaffected by T3 treatment. The rise in resting K+ efflux after 12-24 h of T3 treatment could be partly blocked by dantrolene or trifluoroperazine, indicating that an increase in the cytoplasmic Ca2+ concentration may contribute to the early rise in K+ efflux. It is concluded that the early rise in the resting passive leaks of Na+ and K+ induced by T3 is a major driving force for Na+-K+ pump synthesis.
Microdialysis of adipose tissue and blood for in vivo lipolysis studies
Authors: Arner P. , Bolinder J. , Eliasson A. , Lundin A. , Ungerstedt U.
Published: December 2017

Glycerol levels (lipolysis index) were continuously monitored in intact rats using simultaneous microdialysis of venous blood and subcutaneous adipose tissue. Dialysis probes (0.5 X 4 mm) were implanted and perfused using a microinjection pump. The basal glycerol levels in perfusates of blood and adipose tissue were stable. Intravenous isoproterenol (isoprenaline) increased the glycerol levels in a similar fashion in blood perfusate as compared with plasma and the dialysate of two different adipose tissue probes implanted in the same animal. Isoproterenol included in the adipose tissue dialysis solvent increased the glycerol level in adipose tissue perfusate but not in the blood perfusate; this indicates a local lipolytic effect of catecholamines. Increases in intravenous doses of isoproterenol caused a transient and marked dose-dependent elevation of glycerol in the adipose tissue perfusate and a gradual but less marked rise of glycerol in blood perfusate. This indicates that glycerol kinetics in blood and adipose tissue differ after catecholamine stimulation. In conclusion, microdialysis of blood and subcutaneous adipose tissue offers new and unique possibilities for in vivo lipolysis studies in intact animals.
Regulation of plasma lipid transfer by the high-density lipoproteins
Authors: Tollefson J. H. , Liu A. , Albers J. J.
Published: December 2017

Mechanisms that regulate the activity of the plasma cholesteryl ester transfer protein (lipid protein transfer-I) are poorly understood. We have examined the role of endogenous regulators of the lipid transfer process, in particular the plasma high-density lipoproteins (HDLs), in both humans and two species previously reported to be devoid of cholesteryl ester transfer activity, the rat and the pig. Chromatography of d greater than 1.21 g/ml plasma on phenyl-Sepharose either enhanced (human) lipid transfer activity or unmasked (rat and pig) a nearly completely suppressed lipid transfer activity. The HDLs (either native or delipidated) were shown to be a rich source of a plasma lipid transfer inhibitor protein. Partial purification of the HDL-derived lipid transfer inhibitor protein was achieved by sequential chromatography on phenyl- and DEAE-Sepharose. Additional analysis of plasma from patients with very low (Tangier disease), normal, or very high levels of HDL cholesterol (hyperalphalipoproteinemia) revealed a significant inverse correlation between plasma cholesteryl ester transfer activity and the subjects HDL cholesterol level. These results suggest that circulating levels of the plasma high density lipoproteins may be an important determinant of plasma cholesteryl ester transfer activity, through the function of the HDL-derived lipid transfer inhibitor protein.
No accumulation of glucose in human skeletal muscle during euglycemic hyperinsulinemia
Authors: Katz A. , Nyomba B. L. , Bogardus C.
Published: December 2017

It has been recently suggested that high glucose infusion rates during euglycemic hyperinsulinemia result in accumulation of free glucose in human skeletal muscle (J. Clin. Invest. 76: 357, 1985). To examine this possibility, we performed a euglycemic, hyperinsulinemic clamp together with biopsies from the quadriceps femoris muscle on seven healthy men. Insulin was infused at successive rates of 40 and 400 mU. m-2.min-1, resulting in mean plasma insulin concentrations of 69 +/- 3 and 1,285 +/- 115 (SE) microU/ml, respectively. Glucose infusion rates averaged 7.79 +/- 0.86 and 12.01 +/- 0.77 mg.kg body wt-1.min-1. The total glucose content in muscle averaged 1.72 +/- 0.26, 1.37 +/- 0.21, and 1.65 +/- 0.35 mmol/kg dry wt at rest, and after the low- and high-dose insulin infusions, respectively (P greater than 0.05). Assuming that the plasma glucose concentration reflects the glucose concentration in the extracellular space and that there are 0.3 liters of extracellular water per kilogram dry weight, the intracellular glucose contents are calculated to be 0.15 +/- 0.25, -0.35 +/- 0.21, and -0.06 +/- 0.34 mmol/kg dry wt at rest, and after the low- and high-dose infusions, respectively. None of these values is significantly different from zero. Thus euglycemic hyperinsulinemia does not result in appreciable accumulation of glucose in the muscle of insulin-sensitive men.
Independent stimulation of glucose metabolism and Na+-K+ exchange by insulin in the human forearm
Authors: Ferrannini E. , Taddei S. , Santoro D. , Natali A. , Boni C. , Del Chiaro D. , Buzzigoli G.
Published: December 2017

Insulin promotes potassium uptake into skeletal muscle by stimulating the activity of the Na+-K+ pump. To test whether insulin-induced glucose and potassium uptake are linked processes in vivo, we used the perfused forearm technique in healthy volunteers. Local hyperinsulinemia (125 +/- 11 microU/ml for 100 min) induced a net uptake of glucose and potassium (4.79 +/- 0.61 and 0.76 +/- 0.22 mumol.min-1.100 ml-1 of forearm volume, respectively). When an intra-arterial ouabain infusion (0.72 microgram.min-1.100 ml-1, producing local levels of approximately 0.5 mM) was superimposed on the insulin infusion, potassium uptake was blocked (0.026 +/- 0.190 ml.min-1.100 ml-1, P less than 0.02), and glucose uptake was decreased (to 3.31 +/- 0.34 mumol.min-1.100 ml-1, P less than 0.03). The latter change was explained by a 30% fall in forearm blood flow (from 2.95 +/- 0.10 to 2.01 +/- 0.18 ml.min-1.100 ml-1, P less than 0.001). To separate out the effect of blood flow, in another series of studies forearm blood flow was clamped by co-infusing propranolol and phentolamine (7 and 8 micrograms.min-1.100 ml-1, respectively). Under these conditions of fixed flow (7.0 +/- 0.8 ml.min-1.100 ml-1), ouabain still abolished the stimulatory effect of insulin on potassium uptake but had only a small (and statistically insignificant) effect on forearm glucose extraction (from 20 +/- 2 to 16 +/- 2%, P = N>). We conclude that in human forearm muscle ouabain inhibits Na+-K+ exchange and depresses insulin-induced glucose uptake via an adrenergic-mediated limitation of blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered hepatic fatty acid metabolism in endotoxicosis: effect of L-carnitine on survival
Authors: Takeyama N. , Takagi D. , Matsuo N. , Kitazawa Y. , Tanaka T.
Published: December 2017

The activities of palmitoyl-coenzyme A (CoA) synthetase, carnitine acetyltransferase (CAT), and carnitine palmitoyltransferase (CPT) and the levels of ketone bodies, reduced coenzyme A (CoASH), carnitine, and their esters, which are involved in fatty acid metabolism, in rat liver and plasma were measured after the administration of Escherichia coli lipopolysaccharide (LPS). We also studied the effect of L-carnitine treatment before LPS administration on survival and on hepatic fatty acid metabolism. The activities of CAT and CPT and the concentrations of ketone bodies, CoA, and carnitine derivatives (except for malonyl-CoA) declined in the liver after LPS administration. The activity of palmitoyl-CoA synthetase was changed little after LPS administration, and the level of hepatic malonyl-CoA increased significantly, suggesting that LPS causes activated fatty acids to undergo esterification and lipogenesis rather than oxidation. Treatment of rats with L-carnitine before LPS greatly increased the survival rate, but did not affect enzymes that metabolize fatty acids, CoA, or carnitine derivatives in the liver. Further studies are necessary to elucidate the mechanism of the effect of carnitine on post-LPS survival.