bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfusion index in healthy newborns during critical congenital heart disease screening at 24 hours: retrospective observational study from the USA
Authors: Jegatheesan Priya , Nudelman Matthew , Goel Keshav , Song Dongli , Govindaswami Balaji
Published: December 2017

Objective

To describe the distribution of perfusion index (PI) in asymptomatic newborns at 24 hours of life when screening for critical congenital heart disease (CCHD) using an automated data selection method.

Design

This is a retrospective observational study.

Setting

Newborn nursery in a California public hospital with ~3500 deliveries annually.

Methods

We developed an automated programme to select the PI values from CCHD screens. Included were term and late preterm infants who were screened for CCHD from November 2013 to January 2014 and from May 2015 to July 2015. PI measurements were downloaded every 2 s from the pulse oximeter and median PI were calculated for each oxygen saturation screen in our cohort.

Results

We included data from 2768 oxygen saturation screens. Each screen had a median of 29 data points (IQR 17 to 49). The median PI in our study cohort was 1.8 (95% CI 1.8 to 1.9) with IQR 1.2 to 2.7. The median preductal PI was significantly higher than the median postductal (1.9 vs 1.8, p=0.03) although this difference may not be clinically significant.

Conclusion

Using an automated data selection method, the median PI in asymptomatic newborns at 24 hours of life is 1.8 with a narrow IQR of 1.2 to 2.7. This automated data selection method may improve accuracy and precision compared with manual data collection method. Further studies are needed to establish external validity of this automated data selection method and its clinical application for CCHD screening.
Effects of a school-based stroke education program on stroke-related knowledge and behaviour modification―school class based intervention study for elementary school students and parental guardians in a Japanese rural area
Authors: Kato Suzuka , Okamura Tomonori , Kuwabara Kazuyo , Takekawa Hidehiro , Nagao Masanori , Umesawa Mitsumasa , Sugiyama Daisuke , Miyamatsu Naomi , Hino Tenyu , Wada Shinichi , Arimizu Takuro , Takebayashi Toru , Kobashi Gen , Hirata Koichi , Yokota Chiaki , Minematsu Kazuo
Published: December 2017

Objectives

This study aimed to determine the effect of a stroke education programme on elementary school students and their parental guardians in a rural area in Japan that has high stroke mortality.

Design

School class based intervention study.

Setting

Eleven public elementary schools in Tochigi Prefecture, Japan.

Participants

268 students aged 11–12 years and 267 parental guardians.

Interventions

Students received lessons about stroke featuring animated cartoons and were instructed to communicate their knowledge about stroke to their parental guardians using material (comic books) distributed in the lessons. Stroke knowledge (symptoms, risk factors and attitude towards stroke) and behavioural change for risk factors were assessed at baseline, immediately after the programme and at 3 months. We also evaluated behavioural change for risk factors among parental guardians.

Results

The percentage of students with all correct answers for stroke symptoms, risk factors and the recommended response to stroke was significantly increased at 3 months P<0.001). We observed a significant increase in the percentage of guardians who chose all correct symptoms (P<0.001: 61.0% vs 85.4%) and risk factors (P<0.001: 41.2% vs 59.9%) at 3 months compared with baseline. The percentage of parental guardians with a high behavioural response to improving risk factors was significantly increased at 3 months compared with baseline (P<0.001).

Conclusions

In a rural population with high stroke mortality, stroke education can improve knowledge about stroke in elementary school students and their parental guardians.

Ethics and dissemination

We conducted the intervention as a part of compulsory education; this study was not a clinical trial. This study was approved by the Ethics Committee of the National Cerebral and Cardiovascular Center (M27-026).
Effects of drinking on late-life brain and cognition
Authors: Topiwala Anya , Ebmeier Klaus Peter
Published: December 2017

Alcohol consumption is common in Western countries and has been increasing in older adults. Latest figures from Great Britain suggest 75% of those over 65 years drink, an increase from 71% 10 years ago. Chronic heavy intake is a well-established cause of brain atrophy and dementia, with a recent long-term prospective study from the USA reporting a doubling of the odds of later severe memory impairment in those with a history of an alcohol use disorder. Drinking of moderate amounts has been reported to be protective for brain health in a number of epidemiological studies, including some claims of possibly reducing dementia risk. Rigorous recent research has questioned this belief, with new evidence of harmful associations in moderate drinkers compared with abstainers. This has raised suspicion that reported protective effects of moderate drinking were due to confounding by socioeconomic class and intelligence. Clinicians should look out for cognitive impairment in heavy drinkers, considering that abstinence may induce a degree of clinical improvement. Discussions with patients regarding moderate drinking should be informed by recent research. Health benefits of moderate drinking at least for cognitive function are questionable, and if they exist are probably limited to one unit of alcohol daily with respect to other body systems.
Paths to the unknown: dispersal during the early life of fishes
Authors: Keckeis Hubert , Clemmesen Catriona , Humphries Paul , Sponaugle Su
Published: December 2017

The special issue brings together selected contributions from the 39th Annual Larval Fish Conference hosted by the University of Vienna, Austria, and presents the latest research and understanding of dispersal patterns and processes of early life stages of fishes of various aquatic environments around the world (open ocean, coastal areas, estuaries, and rivers). An important component of this compendium is to indicate new approaches and to outline the importance of integration of information about movements and dispersal for recruitment, population dynamics, species conservation, and management issues.
Norepinephrine storage, distribution, and release in diabetic cardiomyopathy
Authors: Ganguly P. K. , Beamish R. E. , Dhalla K. S. , Innes I. R. , Dhalla N. S.
Published: December 2017

The ability of hearts to store, distribute, and release norepinephrine (NE) was investigated in rats 8 wk after the induction of diabetes by an injection of streptozotocin (65 mg/kg iv). Chronic diabetes was associated with increased content and concentration of NE in heart and in other tissues such as kidney, brain, and spleen. Reserpine or tyramine treatment resulted in depletion of endogenous cardiac NE in control and diabetic rats. The depletion of NE stores at different times after a dose of reserpine was greater in diabetic hearts. On the other hand, NE stores in diabetic hearts were less sensitive than control hearts to low doses of tyramine but were more sensitive to high doses. The uptake of [3H]NE was greater in diabetic hearts in isolated perfused preparations. In comparison with the control values, diabetic hearts showed a decrease in [3H]NE in the granular fraction and an increase in the supernatant fraction. Diabetic hearts also showed an accelerated spontaneous release of [3H]NE. The increased cardiac NE and the uptake and release of NE in diabetic animals were reversible upon treatment with insulin. These results are consistent with the view that sympathetic activity is increased in diabetic cardiomyopathy and indicate that cardiac NE in diabetic rats is maintained at a higher level partly due to an increased uptake of released NE by adrenergic nerve terminals.
Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats
Authors: Carpenter T. O. , Carnes D. L. , Anast C. S.
Published: December 2017

Resistance to vitamin D in magnesium depletion has been observed in humans and in animal studies. Variable levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] have been reported in patients with magnesium depletion, and studies of vitamin D metabolism in states of magnesium depletion have not yielded consistent results. We examined effects of magnesium deprivation on circulating 1,25(OH)2D levels before and after a loading dose of 25-hydroxyvitamin D3 [25(OH)D3], on in vivo conversion of small doses of radiolabeled 25(OH)D3 to 1,25(OH)2D3 in intact rats, and on in vitro 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity in rat renal mitochondria. The effects of magnesium-free media on mitochondrial 1 alpha-hydroxylase activity was examined. Magnesium depletion did not affect in vivo conversion of 25(OH)D to 1,25(OH)2D. In vitro 1 alpha-hydroxylase activity was comparable in magnesium-replete and -deplete animals and was evident in the absence of added magnesium in incubation media. Our in vivo and in vitro studies are consistent with one another and demonstrate that in the rat conversion of 25(OH)D to 1,25(OH)2D is unimpaired in magnesium deficiency. Resistance to vitamin D in magnesium depletion is likely due to the impaired skeletal responsivity to 1,25(OH)2D, as demonstrated in earlier studies.
H+ stimulation of cell-mediated bone resorption in tissue culture
Authors: Goldhaber P. , Rabadjija L.
Published: December 2017

The addition of protons in the form of hydrochloric acid (10.5, 17.2, or 26.6 meq/l resulting in an initial media pH of 7.28, 7.15, and 6.94, respectively) to neonatal mouse calvaria maintained in a chemically defined medium in tissue culture for 1 wk increased calcium release in a dose-response fashion. The same amounts of protons added to the media of devitalized calvaria caused no increase in calcium release into the medium. The net cell-mediated calcium release resulting from the addition of 26.6 meq/l of protons amounted to approximately 50% of the initial calvarial calcium content. Hydroxyproline determinations revealed that active resorption was taking place, wherein both mineral and organic matrix are removed simultaneously. Histological examination of the extensively resorbed calvaria demonstrated the presence of numerous osteoclasts in different stages of bone destruction. The addition of indomethacin (100 ng/ml) strongly inhibited the increase in calcium release by added protons, suggesting that prostaglandin synthesis is involved in the phenomenon. The addition of thyrocalcitonin also inhibited proton-induced calcium release, providing additional evidence that the calcium release from cultures exposed to added protons involved osteoclastic activity.
Fasting-mediated alteration studies in insulin action on lipolysis and lipogenesis in obese women
Authors: Arner P. , Engfeldt P.
Published: December 2017

The effects of fasting on insulin-induced antilipolysis and lipogenesis were investigated in vitro in isolated human fat cells of 11 obese females. Glycerol release and lipogenesis were determined simultaneously in the same test tube and related to methylglucose transport and specific insulin binding. Insulin binding and sensitivity and the responsiveness (maximum effect) of insulin-induced antilipolysis were enhanced by fasting. The latter was strongly correlated with an enhancement in the lipolysis rate. The effects of fasting on antilipolysis were not dependent on the glucose concentration, unlike insulin-stimulated lipogenesis. At 1 mumol/l of glucose, where hexose transport is rate limiting, sensitivity and responsiveness of insulin-induced lipogenesis were inhibited by fasting. Similar results were obtained with methylglucose transport. At 1-10 mmol/l of glucose, where hexose metabolism is rate limiting, insulin stimulated lipogenesis before fasting but was totally ineffective after fasting. In conclusion, fasting induces multiple alterations in insulin action on lipolysis and lipogenesis in adipocytes. Antilipolysis is enhanced because of stimulation at the receptor and postreceptor levels, which may be associated with an enhanced rate of lipolysis. Fasting inhibits the lipogenic effect of insulin due to postreceptor changes involving both transport and metabolism of glucose, making lipogenesis unresponsive to insulin at physiological glucose concentrations.
Differences between in vitro and in vivo degradation of LHRH by rat brain and other organs
Authors: Carone F. A. , Stetler-Stevenson M. A. , May V. , LaBarbera A. , Flouret G.
Published: December 2017

Homogenates of brain, pituitary, liver, lung, ovary, and testes were incubated with [pyro Glu1-3,4-3H]luteinizing hormone-releasing hormone ([3H]LHRH), and the profiles of metabolites generated as a function of time were determined. After 5 min of incubation, 5 was the predominant metabolite in most homogenates. Although the profiles of metabolites varied at different time intervals, metabolites 2, 3, 4, and 5, and in some instances 7 and 9, appeared to form simultaneously and were detectable at 10 min. Neither metabolite 6 nor other larger metabolites formed initially as dominant degradation products. The findings suggest cleavage of LHRH by the simultaneous action of several endopeptidases. After a single vascular transit of [3H]LHRH, metabolites were determined in the venous blood of liver, lung, and brain of rats in vivo. There were no metabolites of [3H]LHRH in venous blood of liver and lung; however, metabolites 2-4 were present in venous blood of the brain. Incubation of rat anterior pituitary cells with [3H]LHRH yielded metabolites 1-4 but not metabolites 5 or 9 as in homogenates. Incubation of [3H]LHRH with porcine follicular granulosa cells resulted in the generation of metabolites 2-7 and 9, similar to the profile in homogenates. Thus, since homogenates contain enzymes of disrupted cells, they do not always reflect mechanisms for in vivo hydrolysis of circulating LHRH. Brain degraded 12.1% of LHRH during a single vascular transit and may account for substantial degradation of the circulating hormone.
Control of compensatory lung growth by adrenal hormones
Authors: Rannels D. E. , Karl H. W. , Bennett R. A.
Published: December 2017

The effects of adrenalectomy and/or in vivo treatment with hydrocortisone acetate (HCA;5 mg X kg-1 X day-1) on lung growth were investigated in control and pneumonectomized rats of 250 g body wt. Left pneumonectomy (day 0) initiated rapid hyperplastic growth of the right lung, which was unaffected by HCA. Similarly, HCA had no effect on lung growth in unoperated control animals. Two weeks after pneumonectomy, right lung dry mass, protein, RNA, and DNA were equal to that in both lungs of unoperated rats. Adrenalectomy 5 days before (day -5) left pneumonectomy increased the rate and extent of right lung growth, but did not change its hyperplastic character. Continuous HCA treatment (days -5 to 14) prevented the adrenalectomy-mediated increase in postpneumonectomy lung growth. "Early" HCA dosing (days -5 to 6) of adrenalectomized-pneumonectomized animals suppressed lung growth to the pneumonectomy level, but from days 7 to 14 growth accelerated to the adrenalectomized-pneumonectomized rate. Conversely, "late" HCA, initiated when adrenalectomized-pneumonectomized animals had restored normal total lung mass (days 6 to 14), quickly reduced right lung growth to rates typical of unoperated controls. The latter effects were not observed unless continuous steroid treatment was provided throughout this interval. The data support a role for glucocorticosteroids in modulation of the accelerated compensatory lung growth initiated by partial resection of the tissue.
Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects
Authors: Rodnick K. J. , Haskell W. L. , Swislocki A. L. , Foley J. E. , Reaven G. M.
Published: December 2017

The present studies were initiated to assess the effect of insulin on muscle, liver, and adipose tissue in eight control and eight physically trained individuals matched for age and body mass index. Results indicated that percent body fat was 53% lower and maximal oxygen consumption 50% higher in physically trained subjects. Although the plasma glucose response to a standard oral glucose challenge was similar in the two groups, the insulin response was significantly lower in the trained individuals (P less than 0.001). Mean (+/- SE) insulin-stimulated glucose uptake, quantified in vivo by the euglycemic hyperinsulinemic clamp technique, was significantly greater in physically trained individuals at steady-state plasma insulin concentrations of approximately 10 microU/ml (3.41 +/- 0.14 vs. 2.73 +/- 0.22 mg.kg fat free mass-1.min-1, P less than 0.05) and 50 microU/ml (13.58 +/- 0.75 vs. 9.82 +/- 0.53 mg.kg fat free mass-1.min-1, P less than 0.001). In addition, mean (+/- SE) hepatic glucose production rate was lower in physically trained subjects at insulin levels of 10 microU/ml (0.63 +/- 0.19 vs. 1.19 +/- 0.22 mg.kg body wt-1.min-1, P less than 0.05) and 50 microU/min (0.18 +/- 0.14 vs. 0.60 +/- 0.17 mg.kg body wt-1.min-1, P less than 0.05). Finally, the ability of insulin to stimulate mean (+/- SE) glucose uptake above basal levels was greater in adipocytes isolated from trained individuals (94 +/- 10 vs. 56 +/- 14 fl.cell-1.s-1, P less than 0.01). On the other hand, no difference in specific binding of insulin to its receptor on monocytes was noted between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous opioids may mediate secondary damage after experimental brain injury
Authors: McIntosh T. K. , Hayes R. L. , DeWitt D. S. , Agura V. , Faden A. I.
Published: December 2017

Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist (Win 44,441-3 [Win-(-)]) with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury.
Reconstructing the rate of appearance of subcutaneous insulin by deconvolution
Authors: Cobelli C. , Mari A. , Del Prato S. , De Kreutzenberg S. , Nosadini R. , Jensen I.
Published: December 2017

In this paper a deconvolution scheme is presented to reconstruct the rate of appearance of subcutaneously injected insulin. Relevant aspects of experiment design are briefly described. Intravenous insulin kinetics are modeled to determine the impulse response of the system. The deconvolution problem is not ill conditioned and is solved using a least-squares method without imposing constraints on the input. An estimate of the error of the reconstructed input is provided. The reliability of the deconvolution scheme is tested by means of an independent validation study. Finally, the different sources of error that affect the method are discussed, and a figure of the global error is derived.
[3H]-[Thr4,Gly7]OT: a highly selective ligand for central and peripheral OT receptors
Authors: Elands J. , Barberis C. , Jard S.
Published: December 2017

Oxytocin receptors in rat hippocampal synaptic plasma membranes were compared with mammary gland and uterine oxytocin receptors. For this purpose, a highly specific oxytocic agonist [Thr4,Gly7]oxytocin was tritiated. We demonstrated that this ligand labels oxytocin receptors selectively. Scatchard analyses revealed a high affinity for all the oxytocin receptors investigated, with equilibrium dissociation constants between 1.0 and 2.0 nM. Binding appeared to take place at a single population of receptor sites. Competition experiments confirmed the high affinity of arginine vasopressin for hippocampal oxytocin receptors but also revealed that mammary gland and uterine oxytocin receptors do not discriminate more efficiently between oxytocin and arginine vasopressin. This lack in specificity is not affected by applying different concentrations of Mg ions.
Physiological role of glucocorticoids on rat serum and liver metallothionein in basal and stress conditions
Authors: Hidalgo J. , Giralt M. , Garvey J. S. , Armario A.
Published: December 2017

Serious contradictions exist at present in our understanding of the physiological role of glucocorticoids on the synthesis of the metal-binding protein, metallothionein (MT). In addressing this problem, we have examined in vivo the role of glucocorticoids on liver and serum MT levels in the rat under a spectrum of experimental conditions. The experiments confirm that stress has a major positive effect on hepatic MT levels. It was found that adrenocorticotropic hormone (ACTH) administration has an inhibitory effect on hepatic MT levels in response to restraint stress and that adrenalectomy (ADX) leads to an increase in basal MT levels and in MT levels in response to acute and chronic immobilization stress. Similar results followed treatment with the glucocorticoid receptor blocker, RU 486. The effect of ADX was abolished by corticosterone replacement. The relations found among hepatic MT, serum MT, and glucocorticoid concentrations indicate that in some circumstances glucocorticoids have a permissive role in mobilizing MT from tissues to serum and that in physiological conditions corticosterone has an inhibitory role in the maintenance of hepatic MT levels.
Change of insulin action with aging in conscious rats determined by euglycemic clamp
Authors: Nishimura H. , Kuzuya H. , Okamoto M. , Yoshimasa Y. , Yamada K. , Ida T. , Kakehi T. , Imura H.
Published: December 2017

To clarify the mechanism responsible for age-related changes in insulin action, the euglycemic clamp technique was performed with graded doses of insulin in conscious rats aged 2, 4, 10, and 20 mo. Insulin binding (IB) to muscle membranes was also studied. Maximal response of insulin-induced glucose disappearance rate (Rd) was decreased significantly between 2 and 4 mo of age. Dose-response curves shifted to the right progressively up to 20 mo of age. However, IB to the muscle membrane diminished between 1 and 4 mo of age without a decrease thereafter. When Rd was plotted against insulin bound to the membranes, the resulting curves shifted to the right with aging, suggesting a coupling defect between the binding and effector unit. In conclusion, insulin action alters in rats between 2 and 20 mo of age. The most pronounced impairment in IB and maximal response of insulin-induced Rd occurs during early life stage (through maturation) and then a coupling defect seems to be superimposed with further aging. However, we cannot exclude the possibility that these changes may be secondary to obesity or reduced physical activity, rather than aging per se.
LH subunit mRNA concentrations during LH surge in ovariectomized estradiol-replaced rats
Authors: Haisenleder D. J. , Barkan A. L. , Papavasiliou S. , Zmeili S. M. , Dee C. , Jameel M. L. , Ortolano G. A. , el-Gewely M. R. , Marshall J. C.
Published: December 2017

In cycling rats, pituitary concentrations of luteinizing hormone (LH) beta-subunit mRNA increase two- to threefold before the afternoon proestrus LH surge without a corresponding increase in alpha-subunit mRNA. Estradiol (E2) treatment is known to allow expression of daily LH surges in ovariectomized (OVX) rats, and the timing, magnitude, and duration of LH secretion is similar to the LH surge on proestrus. The present study was conducted to examine whether the regulation of LH subunit mRNAs during the LH surge in OVX-E2-treated rats is similar to that present on proestrus. Female Holtzman rats were OVX and Silastic implants containing E2 were inserted subcutaneously under ether anesthesia. Some animals received bromocriptine (0.6 mg sc, twice/day beginning 1 h before surgery). On the 2nd day after surgery, groups of animals (n = 4-10/group) were decapitated at intervals between 1000 and 2100. LH and prolactin (PRL) levels were measured in trunk blood. LH subunit mRNA concentrations in the pituitaries were measured by dot-blot hybridization assay. In OVX-E2 rats the LH surge occurred at 1830 and was accompanied by a selective twofold increase in alpha-subunit mRNA (from 266 +/- 18 to 459 +/- 61 pg cDNA bound/100 micrograms pituitary DNA) and maximum values were present at 1730. LH beta-subunit mRNA (m = 29 +/- 1 pg cDNA bound/100 micrograms pituitary DNA) was unchanged throughout the day. Bromocriptine treatment resulted in the suppression of serum PRL (m = 23 +/- 2 ng/ml) and the LH surge was delayed by 1-1.5 h and somewhat blunted.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II causes a dual effect on potassium permeability in adrenal glomerulosa cells
Authors: Lobo M. V. , Marusic E. T.
Published: December 2017

In previous studies it was shown that angiotensin II causes a Ca-dependent increase in the K permeability of bovine adrenal glomerulosa cells [Am. J. Physiol. 250 (Endocrinol. Metab. 13): E125-E130, 1986]. Here we show that angiotensin II causes a significant and prolonged reduction in the 86Rb release immediately after the transient rise in 86Rb efflux. This inhibition was dose related. Apamin (100 nM) and tetraethylammonium (10 mM) completely abolished the initial transient rise in 86Rb efflux without affecting the latter sustained phase of reduced radioisotope release. On the contrary, the effect of angiotensin II on the second phase was absent when Ca was removed from the perifusion medium or replaced with Sr, but the effect on the early transient phase of 86Rb efflux was maintained in the absence of external Ca. An additional finding was the increased coefficient rate of 86Rb efflux that occurred when the cells were depolarized with 12 mM K. However, this effect was not observed when the inhibitory phase due to angiotensin II was fully developed and Ca was present in the external media. On the other hand, the biphasic effect of angiotensin II was still present in depolarized cells. These results suggest that angiotensin II may modulate membrane potential by changes in K permeability of the bovine adrenal glomerulosa cells.
Episodic release of insulin by rat pancreas: effects of CNS and state of satiety
Authors: Safarik R. H. , Joy R. M. , Curry D. L.
Published: December 2017

This study reports that insulin is secreted in an episodic manner in rats and that the characteristics of its release can be modified by the central nervous system (CNS) and state of satiety. The pancreata of male Sprague-Dawley rats were perfused using the in situ brain-pancreas technique under urethan anesthesia. Episodic insulin release under non-fasted conditions was not altered by the presence or absence of CNS innervation to the pancreas. Under these conditions the interpeak period was 5.9 and 6 min, respectively, and cycle length was 3.7 and 4 min. However, perfusions that were performed following an overnight fast demonstrated that the CNS is capable of modulating episodic insulin release. After fasting, when comparing CNS-ablated with -intact preparations, the period was shortened from 5.2 to 4.1 min (P less than 0.05), and the number of episodes per 90-min perfusion increased from 16.0 to 19.0 (P less than 0.05) when the pancreas was innervated by the CNS. Additionally, the effect of fasting on denervated pancreata resulted in a shortening of the cycle length, which was prevented when the CNS was functional. These results demonstrate that episodic insulin release can be modified by metabolic conditions and are subject to mediation by the CNS.
Choice of infusion-sampling mode for tracer studies of free fatty acid metabolism
Authors: Jensen M. D. , Rogers P. J. , Ellman M. G. , Miles J. M.
Published: December 2017

To determine the preferred infusion-sampling mode for isotopic studies of free fatty acid (FFA) metabolism, tracer [( 14C]palmitate) was infused into the left ventricle of five anesthetized dogs, and tracee ([3H]palmitate) was infused into three separate peripheral veins of each dog. The [14C]palmitate specific activity (SA) was lower in mixed venous than arterial blood, and [3H]palmitate SA was equal in both sites. The actual infusion rate of [3H]palmitate [2.15 +/- 0.31 X 10(5) disintegrations/min (dpm).kg-1.min-1] could be accurately predicted (2.14 +/- 0.32 X 10(5) dpm.kg-1.min-1) using the known [14C]palmitate infusion rate and the arterial plasma [14C]-to-[3H]palmitate ratio. In contrast, the mixed venous [14C]-to-[3H]palmitate ratio resulted in overestimates (P less than 0.05) of the actual [3H]palmitate infusion rate. In summary, venous tracer infusion with arterial blood sampling for FFA tracer studies provides the most accurate estimates of tracee rate of appearance.
Effects of age on metabolic responses to acute and chronic stress
Authors: Odio M. R. , Brodish A.
Published: December 2017

The effect of age on the capacity of an organism to mobilize glucose and free fatty acids during stress and to adapt these responses from an acute to a chronic stress situation is not known. The purpose of this study was to determine whether aging impaired the capacity to 1) raise glucose and free fatty acid levels and suppress insulin release in acute stress situations and 2) develop adaptation of these responses to exposure to chronic stress. Our results indicate that 6-mo-old rats (young) trained to escape electric shock (short-term modulation) showed greater acute stress-induced hyperglycemic, hypoinsulinemic, and lipolytic responses than untrained young rats. By contrast, in 22-mo-old rats (old), responses of trained and untrained animals were not different. In the chronic stress (long-term adaptation) experiments, it was found that 1) adaptation of stress-induced hyperglycemia occurred at a faster rate in young than in old animals; 2) in young but not in aged rats, a strong positive correlation was observed between adaptation of stress-induced hyperglycemia and hypoinsulinemia; and 3) in young rats, stress-induced lipolytic responses declined proportionately to the duration of chronic stress exposure, whereas by contrast in chronically stressed aged rats steady-state levels of free fatty acids were not raised during exposure to stress. Thus we conclude that 1) glucose intolerance may play a key role in the altered stress-induced metabolic responses of aged rats; 2) with age, there is a loss of plasticity in physiological adaptive response mechanisms associated with metabolic responses to stress.
Mechanism of insulin action on glucose transport in rat skeletal muscle
Authors: Sternlicht E. , Barnard R. J. , Grimditch G. K.
Published: December 2017

This study was designed to examine the effect of insulin stimulation on glucose transport in rat skeletal muscle. Sarcolemmal vesicles (SL) were isolated from the gastrocnemius-plantaris and quadriceps muscles from insulin-stimulated and control groups. The insulin-stimulated group received an intravenous insulin injection (1 U/kg) 10 min before isolation. The early time course of specific D-glucose transport was linear through 2 s. Michaelis-Menten kinetics at 1.5 s indicated that the Vmax for glucose transport was increased after insulin stimulation compared with controls (4,424 +/- 668 vs. 1,366 +/- 124 pmol.mg protein -1.s-1), whereas the Km remained unchanged (19.4 +/- 0.6 vs. 21.6 +/- 3.1 mM). Scatchard plots for the D-glucose-inhibitable class of cytochalasin B binding sites indicated that insulin stimulation increased the number of binding sites in the SL vesicles (9.3 +/- 0.6 vs. 5.5 +/- 0.3 pmol/mg protein) without altering the Kd (48 +/- 3 vs. 46 +/- 3 nM). That the increase in Vmax was greater than the increase in cytochalasin B binding sites indicates that insulin stimulation caused an increase in the turnover rate of existing transport molecules as well as an increase in the total number of SL glucose transport molecules.
Regulation of glycogen synthase in muscle and adipose tissue during fasting and refeeding
Authors: Antwi D. , Youn J. H. , Shargill N. S. , Lesikar D. D. , Kaslow H. R.
Published: December 2017

Using immunoblot analysis, we examined the electrophoretic mobility of glycogen synthase from rat skeletal muscle and adipose tissue. Extracts from muscle freeze clamped in situ contained at least three forms of synthase with different electrophoretic mobilities. Extracts from adipose tissue also contained multiple forms but lacked the form with greatest mobility found in the muscle extracts. Phosphorylation at multiple sites of glycogen synthase is known to deactivate the enzyme and retard its electrophoretic mobility in sodium dodecyl sulfate gels. These results suggest that there is very little or no dephosphorylated glycogen synthase in adipose tissue and that phosphorylated forms of glycogen synthase synthesize adipose tissue glycogen. Relative to control, it is known that fasting decreases and refeeding increases glucose incorporation into glycogen in rat epididymal adipose tissue but not skeletal muscle incubated in vitro in the presence of insulin. Fasting did not change the electrophoretic pattern of muscle synthase but decreased the relative amount of adipose tissue forms with greater mobility. Refeeding increased above control the relative amount of adipose tissue synthase with greater mobility. These results indicate that changes in the phosphorylations that retard mobility contribute to the effects of fasting and refeeding on adipose tissue glycogen metabolism.
Metabolism of intact parathyroid hormone in isolated perfused rat liver and kidney
Authors: Daugaard H. , Egfjord M. , Olgaard K.
Published: December 2017

Metabolism of synthetic human parathyroid hormone (PTH) 2 X 10(-10) to 5 X 10(-9) M was studied in 16 isolated perfused rat kidneys and 12 isolated perfused rat livers. Organ clearances were measured by assays specific for intact PTH. Production of fragments was analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassays specific for NH2-terminal, midmolecule, and COOH-terminal PTH. The livers cleared intact PTH and NH2-terminal immunoreactive PTH (iPTH) at the same rate. Midmolecule iPTH was cleared significantly (P less than 0.001) slower, as was COOH-terminal iPTH (P less than 0.005), and HPLC studies demonstrated production of midmolecule/COOH-terminal PTH fragments, while no NH2-terminal fragments were found. Clearance in the kidneys of intact PTH and of NH2-terminal, midmolecule, and COOH-terminal iPTH was not significantly different from clearance of inulin. No clearance of intact PTH was found in nonfiltering kidneys. HPLC studies did not demonstrate release of any PTH fragments from the kidneys. In conclusion, the liver was not selective for intact PTH, and differential hepatic clearance, possibly together with direct glandular secretion, may contribute to the predominance of COOH-terminal PTH fragments in plasma.
Estimating false-positive and false-negative errors in analyses of hormonal pulsatility
Authors: Van Cauter E.
Published: December 2017

Previous studies evaluating computer algorithms for endocrine pulse detection have estimated the rate of false-positive pulses in series of purely random variations (i.e., “noise”) and have determined pulse-detection criteria associated with low levels of such false-positive rates. The present study investigates the relationship between the false-positive rate and the sizes of the false-positive and false-negative errors on pulse frequency for series including both pulses and noise. The algorithm used (ULTRA) proceeds by eliminating all peaks of concentration for which either the increment or the decrement does not exceed a threshold expressed in multiples of the local intra-assay coefficient of variation. A total of 336 computer-generated series was analyzed using thresholds of two and three coefficients of variation. The effects of noise level, pulse frequency, pulse amplitude, and presence of a base-line variation on the sizes of the false-positive and false-negative errors were evaluated. The false-positive rate in noise series exceeded the false-positive rate by a 4- to 10-fold factor in series including at least 8 pulses/100 samples. When pulse frequency increased, the false-positive error decreased, but the false-negative error increased. In series with more than 8 pulses/100 samples, the use of thresholds aimed at maintaining the false-positive rate in noise series below 1% resulted in a false-negative error in excess of 20%. In conclusion, for hormonal profiles that include 8 or more pulses/100 samples, the use of pulse-detection criteria tailored to minimize the false-positive rate in noise series may result in an underestimation of pulse frequency.
Effect of short-term DHEA administration on liver metabolism of lean and obese rats
Authors: Mohan P. F. , Cleary M. P.
Published: December 2017

Lean and obese Zucker rats, 7-8 wk of age, were treated with dehydroepiandrosterone (DHEA) for either 3 or 7 days to determine the initial cellular event(s) that might be responsible for the antiobesity activity of DHEA. Epididymal, retroperitoneal, and brown adipose tissue weights were unaltered by either 3 or 7 days of DHEA treatment. Liver weight was not affected by 3 days of treatment but was 13 and 18% higher in 7-day DHEA-treated lean and obese rats, respectively, compared with their corresponding control group. Mitochondrial state 3 respiration rates with glutamate-malate and succinate as substrates were elevated by an average of 35% in 3- and 7-day DHEA-treated obese rats and by 15-20% in 7-day DHEA-treated lean rats compared with rates obtained in the corresponding control groups. State 3 respiration was not affected in 3-day DHEA-treated lean rats compared with control lean rats. The specific activities of long-chain fatty acyl-coenzyme A synthase and hydrolase and the levels of free CoA were increased by severalfold in cellular fractions of both DHEA-treated lean and obese rats compared with their respective control group. Hepatic malic enzyme activity, which was shown earlier to be elevated with long-term DHEA treatment, was unaltered by either 3 or 7 days of DHEA administration. The above results suggest the involvement of mitochondrial respiration and fatty acid deacylation/reacylation in the antiobesity mechanism of action of DHEA.
Physiological insulin action is opposed by beta-adrenergic mechanisms in dogs
Authors: Werther G. A. , Joffe S. , Artal R. , Sperling M. A.
Published: December 2017

To investigate the possible role of adrenergic mechanisms in modulating glucose homeostasis during physiological insulin changes, we studied the effects of alpha-, beta-, or combined alpha- and beta-adrenergic blockade on glucose production (Ra) and utilization (Rd) via isotope ([3-(3)H]glucose) dilution during nonstressful, nonhypoglycemic conditions in response to physiological insulin changes in conscious dogs. Without adrenergic blockade, infusion of insulin at 0.275 mU.kg-1.min-1 (control) caused glucose to fall from 92 +/- 4 to 82 +/- 4 mg/dl over 30 min, because of transient fall in Ra from 2.8 +/- 0.4 to 2.3 +/- 0.3 mg.kg-1.min-1, which recovered to base line by 30 min. There was a later rise in Rd to 3.9 +/- 0.4 mg.kg-1.min-1 at 45 min, but no counter-regulatory hormonal changes (glucagon, cortisol, epinephrine, and norepinephrine) to account for these findings in glucose kinetics. alpha-Blockade alone led to an initial rise in base-line insulin and consequent fall in glucose, associated with a transient fall in Ra but no change in Rd; infusion of insulin led to a further small fall in glucose, with no change in Ra, but with a rise at 30 min in Rd similar to controls. beta-Blockade alone led to an initial fall in insulin and modest rise in glucose; insulin infusion led to a greater rate of fall in glucose than in controls (from 112 +/- 6 to 78 +/- 7 mg/dl over 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian variation in response to CRF-41 and AVP
Authors: Graf M. , Fischman A. J. , Kastin A. J. , Moldow R. L.
Published: December 2017

The diurnal response to ovine corticotropin-releasing factor (CRF-41), arginine vasopressin (AVP), and adrenocorticotropic hormone (ACTH) was studied in rats in which the endogenous release of CRF was blocked by chlorpromazine, morphine sulfate, and pentobarbital sodium. This procedure resulted in a markedly attenuated circadian rhythm at base-line levels of plasma corticosterone and ACTH. Decreased pituitary responsiveness to CRF-41 and AVP at 0400 compared with 1600 was observed. The plasma corticosterone response 30 min after intravenous injection of ovine CRF-41 (0.1 microgram/kg) or AVP (5.0 micrograms/kg) remained nearly constant over the major portion of the 24-h light-dark cycle. However, in the early morning (0400), 2 h before lights on, there was an approximately threefold decrease in response. The time of this decrease in response coincided with the normal decline in the concentrations of plasma corticosterone and ACTH. Rats exposed to constant darkness for 10 days continued to show a significantly greater response to CRF or AVP at 1600 than at 0400. In contrast, rats exposed to constant light for 10 days failed to demonstrate a differential response to CRF or AVP at different times of the day. These results demonstrate that there is a diurnal rhythm in pituitary response to CRF and AVP.
Increased SR phospholipid N-methylation in skeletal muscle of diabetic rats
Authors: Taira Y. , Ganguly P. K. , Panagia V. , Dhalla N. S.
Published: December 2017

Phosphatidylethanolamine (PE) N-methylation was studied in skeletal muscle sarcoplasmic reticulum (SR) 6 wk after the induction of experimental diabetes in rats by an injection of streptozocin (65 mg/kg iv). A significant increase in the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (AdoMet) into intramembranal PE was observed in diabetic preparations at 0.055 microM AdoMet, whereas the methylation activity was unaltered at 10 and 150 microM AdoMet concentrations. The increase in PE N-methylation activity was not evident until 28 days after streptozocin injection and was normalized by a 2-wk treatment of diabetic animals with insulin. In the presence of 10 microM of ATP and low concentrations of Ca2+ (0.1 microM), PE N-methylation was maximally activated, but the percent increase was similar in control, diabetes, and insulin-treated diabetes; at 100 microM Ca2+, however, N-methylation activity was depressed only in diabetic preparations. Calmodulin inhibitors such as compound 48/80 and calmidazolium (compound R24571) abolished the effect of Ca2+ and ATP on PE N-methylation in all three groups. Sarcolemmal (SL) PE N-methylation in diabetic skeletal muscle was also found to be increased at 0.055 microM AdoMet. The results suggest that intramembranal calmodulin may participate in regulating PE N-methylation in skeletal muscle membranes, but it may not be responsible for the high N-methylation activity in diabetic rats.
In vivo characterization of insulin uptake by dog renal cortical epithelium
Authors: Whiteside C. I. , Lumsden C. J. , Silverman M.
Published: December 2017

In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: [3H]dextran greater than 70 kDa (plasma reference), [14C]inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below [14C]inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching [14C]inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM.
Modulation of rat testes lipid composition by hormones: effect of PRL and hCG
Authors: Sebokova E. , Wierzbicki A. , Clandinin M. T.
Published: December 2017

The effect of prolactin (PRL) and human chorionic gonadotropin (hCG) administration for 7 days on the composition and function of rat testicular plasma membrane was investigated. Refractory state in Leydig cells desensitized by hCG decreased the binding capacity for 125I-labeled hCG and also luteinizing hormone (LH)-induced adenosine 3',5'-cyclic monophosphate (cAMP) and testosterone production. In testicular membranes of hCG-treated animals, a depletion of cholesterol and an increase in total phospholipid content was observed after gonadotropin injection, thereby decreasing the cholesterol-to-phospholipid ratio. Injection of high doses of PRL had no effect on the binding capacity or affinity of the LH-hCG receptor but decreased the response of Leydig cells to LH in terms of cAMP and testosterone synthesis. PRL also increased total and esterified cholesterol and decreased free cholesterol and membrane phospholipid content. The fatty acid composition of testicular lipids was significantly and selectively influenced by both hormonal treatments. These observations suggest that metabolism of cholesterol and long-chain polyunsaturated fatty acids in testicular tissue is affected by chorionic gonadotropin and PRL and may provide the mechanism for regulating steroidogenic functions.