scholarly journals Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens

2007 ◽  
Vol 30 (3) ◽  
pp. 282-299 ◽  
Author(s):  
Richard R. Almon ◽  
Debra C. DuBois ◽  
Zhenling Yao ◽  
Eric P. Hoffman ◽  
Svetlana Ghimbovschi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Response ◽  
Data Sets ◽  
Gene Chips ◽  
Glucocorticoid Response ◽  
Constant Rate ◽  
Dosing Regimens ◽  
Chronic Corticosteroid ◽  
Temporal Profiles ◽  
Rate Infusion

The transcriptional response of skeletal muscle to chronic corticosteroid exposure was examined over 168 h and compared with the response profiles observed following a single dose of corticosteroid. Male adrenalectomized Wistar rats were given a constant-rate infusion of 0.3 mg·kg−1·h−1 methylprednisolone for up to 7 days via subcutaneously implanted minipumps. Four control and forty drug-treated animals were killed at ten different time points during infusion. Liver total RNAs were hybridized to 44 individual Affymetrix REA230A gene chips. Previously, we described a filtration approach for identifying genes of interest in microarray data sets developed from tissues of rats treated with methylprednisolone (MPL) following acute dosing. Here, a similar approach involving a series of three filters was applied sequentially to identify genes of interest. These filters were designed to eliminate probe sets that were not expressed in the tissue, not regulated by the drug, or did not meet defined quality control standards. Filtering eliminated 86% of probe sets, leaving a remainder of 2,316 for further consideration. In a previous study, 653 probe sets were identified as MPL regulated following administration of a single (acute) dose of the drug. Comparison of the two data sets yielded 196 genes identified as regulated by MPL in both dosing regimens. Because of receptor downregulation, it was predicted that genes regulated by receptor-glucocorticoid response element interactions would exhibit tolerance in chronic profiles. However, many genes did not exhibit steroid tolerance, indicating that present perspectives on the mechanism of glucocorticoid action cannot entirely explain all temporal profiles.

scholarly journals A Microarray Analysis of the Temporal Response of Liver to Methylprednisolone: A Comparative Analysis of Two Dosing Regimens

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2209-2225 ◽  
Author(s):  
Richard R. Almon ◽  
Debra C. DuBois ◽  
William J. Jusko
Keyword(s):  
Drug Infusion ◽  
Gene Chips ◽  
Product Function ◽  
Male Wistar Rats ◽  
Dosing Regimens ◽  
Single Bolus Dose ◽  
Temporal Profiles ◽  
Microarray Analyses ◽  
Gene Product Function ◽  
Glucocorticoid Action

Microarray analyses were performed on livers from adrenalectomized male Wistar rats chronically infused with methylprednisolone (MPL) (0.3 mg/kg·h) using Alzet mini-osmotic pumps for periods ranging from 6 h to 7 d. Four control and 40 drug-treated animals were killed at 10 different times during drug infusion. Total RNA preparations from the livers of these animals were hybridized to 44 individual Affymetrix REA230A gene chips, generating data for 15,967 different probe sets for each chip. A series of three filters were applied sequentially. These filters were designed to eliminate probe sets that were not expressed in the tissue, were not regulated by the drug, or did not meet defined quality control standards. These filters eliminated 13,978 probe sets (87.5%) leaving a remainder of 1989 probe sets for further consideration. We previously described a similar dataset obtained from animals after administration of a single dose of MPL (50 mg/kg given iv). That study involved 16 time points over a 72-h period. A similar filtering schema applied to the single-bolus-dose dataset identified 1519 probe sets as being regulated by MPL. A comparison of datasets from the two different dosing regimens identified 358 genes that were regulated by MPL in response to both dosing regimens. Regulated genes were grouped into 13 categories, mainly on gene product function. The temporal profiles of these common genes were subjected to detailed scrutiny. Examination of temporal profiles demonstrates that current perspectives on the mechanism of glucocorticoid action cannot entirely explain the temporal profiles of these regulated genes.

Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism

1986 ◽  
Vol 111 (4) ◽  
pp. 516-521
Author(s):  
Nina Clausen ◽  
Per-Eric Lins ◽  
Ulf Adamson ◽  
Bertil Hamberger ◽  
Suad Efendić
Keyword(s):  
Growth Hormone ◽  
Insulin Infusion ◽  
Primary Hypothyroidism ◽  
Constant Rate Infusion ◽  
Counterregulatory Hormones ◽  
Insulin Metabolism ◽  
Hormonal Responses ◽  
Glucose Levels ◽  
Constant Rate ◽  
Rate Infusion

Abstract. Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counterregulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32–52 years, TSH-values 66–200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin, C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.

Pharmacokinetics and pharmacodynamics of a constant rate infusion of fentanyl (5 μg/kg/h) in awake cats

2014 ◽  
Vol 75 (8) ◽  
pp. 716-721 ◽  
Author(s):  
Barbara Ambros ◽  
Jane Alcorn ◽  
Tanya Duke-Novakovski ◽  
Alexander Livingston ◽  
Patricia M. Dowling
Keyword(s):  
Pharmacokinetics And Pharmacodynamics ◽  
Constant Rate Infusion ◽  
Constant Rate ◽  
Awake Cats ◽  
Rate Infusion

HIF-1α in endurance training: suppression of oxidative metabolism

2007 ◽  
Vol 293 (5) ◽  
pp. R2059-R2069 ◽  
Author(s):  
Steven D. Mason ◽  
Helene Rundqvist ◽  
Ioanna Papandreou ◽  
Roger Duh ◽  
Wayne J. McNulty ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Oxidative Metabolism ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Oxidative Capacity ◽  
Pyruvate Dehydrogenase Kinase ◽  
Amp Activated Protein Kinase ◽  
Training Protocol

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1α (HIF-1α), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1α in endurance training, we have created mice specifically lacking skeletal muscle HIF-1α and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1α null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1α null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1α null muscles. Additionally, HIF-1α null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1α target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1α causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1α in normal tissue.

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep

2012 ◽  
Vol 171 (5) ◽  
pp. 125-125 ◽  
Author(s):  
M. del Mar Granados ◽  
J. Manuel Domínguez ◽  
A. Fernández-Sarmiento ◽  
F. Javier Funes ◽  
J. Morgaz ◽  
...  
Keyword(s):  
Constant Rate Infusion ◽  
Constant Rate ◽  
Rate Infusion

scholarly journals CHLOROPLAST GENETICS OF CHLAMYDOMONAS. III. CLOSING THE CIRCLE

Genetics ◽  
1976 ◽  
Vol 83 (2) ◽  
pp. 341-354
Author(s):  
Burt Singer ◽  
Ruth Sager ◽  
Zenta Ramanis
Keyword(s):  
Genetic System ◽  
Time Interval ◽  
Data Sets ◽  
Mapping Data ◽  
Regression Problem ◽  
Mapping Procedure ◽  
Pooled Data ◽  
Constant Rate ◽  
Single Cross ◽  
Chloroplast Genetics

ABSTRACT A novel mapping procedure is presented for organelle genes or any other genetic system exhibiting a measurable frequency of exchanges occurring at a constant rate over a measurable time interval. For a set of markers in a multiply-marked cross, the exchange rates measure relative map distances from a centromere-like attachment point. With this method, we present mapping data and a linear map of genes in the chlcroplast genome of Chlamydomonas. The data are plotted as log (percent remaining heterozygotes) against time and map distances are taken as proportional to slope. A statistical method which is an adaptation of jackknife methodology to a regression problem was developed to estimate slope values. A single line is fitted to pooled data for each marker from several crosses, and then lines are re-fit to a series of pooled data sets in each of which the observations from a single cross have been omitted. From these data sets a final summary slope is computed as well as a statement of its variability. The relative positions of new markers present in single crosses can then be estimated utilizing data from many crosses. The method does not distinguish between one-armed and two-armed linear or circular maps. However, evaluation of this map in conjunction with cosegregation frequency data (Sager and Ramanis 1976b) provides unambiguous evidence of the genetic circularity of the Chlamydomonas chloroplast genome.

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