scholarly journals The Deoxyglucose Method in the Ferret Brain. I. Methodological Considerations

1989 ◽  
Vol 9 (1) ◽  
pp. 35-42 ◽  
Author(s):  
C. Redies ◽  
M. Diksic
Keyword(s):  
Glucose Utilization ◽  
Order Kinetic ◽  
Tracer Injection ◽  
Rate Limiting Step ◽  
Constant Determination ◽  
Lumped Constant ◽  
Methodological Considerations ◽  
Rate Limiting ◽  
The Brain ◽  
Deoxyglucose Method

In the brain of the anesthetized ferret, the 2-deoxyglucose (2-DG) transfer rate constants required to determine cerebral glucose utilization by the deoxyglucose method were calculated from regional gray matter time-radioactivity curves measured for 180 min after tracer injection. Results suggest that loss of metabolized tracer from brain occurs at a rate of about 1%/min for the first 180 min after injection if the rate constant of the rate-limiting step for loss of metabolized tracer ( k*4) represents a first-order kinetic process. A simulation experiment shows that, whether k*4 is assumed to be 0 or 0.01 min−1, has a negligible influence on glucose utilization rates obtained in conventional 45 min autoradiographic experiments provided that the entire analysis, including lumped constant determination, is carried out in a consistent way. The 2-DG lumped constant for k*4 = 0 is 0.54, and 0.68 for k*4 = 0.01 min−1.

scholarly journals The Deoxyglucose Method in the Ferret Brain. II. Glucose Utilization Images and Normal Values

1989 ◽  
Vol 9 (1) ◽  
pp. 43-52 ◽  
Author(s):  
C. Redies ◽  
M. Diksic ◽  
Y. L. Yamamoto
Keyword(s):  
Rate Constants ◽  
Glucose Utilization ◽  
Normal Values ◽  
Brain Size ◽  
Experimental Period ◽  
Brain Structures ◽  
Rate Limiting Step ◽  
Rate Limiting ◽  
The Brain ◽  
Deoxyglucose Method

To measure cerebral glucose utilization with the autoradiographic deoxyglucose method, the tracer transfer rate constants and lumped constants must be known. 2-Deoxyglucose (2-DG) and fluorodeoxyglucose (FDG) constants were determined in 18 gray and white matter brain structures of the anesthetized ferret. The ferret is a domestic carnivore particularly suitable for deoxyglucose studies because of its small brain size and low body weight. The average gray matter rate constants for tracer transfer across the blood-brain barrier are similar for 2-DG and FDG in the ferret brain ( K*1 = 0.21 ml/g/min and k*2 = 0.39 min−1). The rate constant for the rate-limiting step of tracer phosphorylation, k*3, is 1.6 times higher for FDG than for 2-DG (0.21 vs. 0.13 min−1). Loss of metabolized tracer is about 1–1.5%/min throughout the ferret brain for both tracers as estimated for a 180 min experimental period. Taking into account this loss, the lumped constant is 0.92 for FDG and 0.68 for 2-DG. Glucose utilization values in the brain of the anesthesized ferret range from 33 μmol/100 g/min in the corpus callosum to 104 μmol/100 g/min in the caudate nucleus. Representative glucose utilization images of coronal sections of the ferret brain are shown. Brain structures are identified on the same slices counterstained with thionin.

scholarly journals The Lumped Constant of the Deoxyglucose Method in Hypoglycemia: Effects of Moderate Hypoglycemia on Local Cerebral Glucose Utilization in the Rat

1990 ◽  
Vol 10 (4) ◽  
pp. 499-509 ◽  
Author(s):  
Sumio Suda ◽  
Mami Shinohara ◽  
Makoto Miyaoka ◽  
Giovanni Lucignani ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Plasma Glucose Concentration ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Glucose Utilization ◽  
Lumped Constant ◽  
Arterial Plasma ◽  
The Brain ◽  
Deoxyglucose Method

The applicability of the [14C]deoxyglucose method for measuring local cerebral glucose utilization (lCMRglc) has been extended for use in hypoglycemia by determination of the values of the lumped constant to be used in rats with plasma glucose concentrations ranging from approximately 2 to 6 m M. Lumped constant values were higher in hypoglycemia and declined from a value of 1.2 at the lowest arterial plasma glucose level (1.9 m M) to about 0.48 in normoglycemia. The distribution of glucose, and therefore also of the lumped constant, was found to remain relatively uniform throughout the brain at the lowest plasma glucose levels studied. lCMRglc in moderate, insulin-induced hypoglycemia (mean arterial plasma glucose concentration ± SD of 2.4 ± 0.3 m M) was determined with the appropriate lumped constant corresponding to the animal's plasma glucose concentration and compared with the results obtained in six normoglycemic rats. The weighted average rate of glucose utilization for the brain as a whole was significantly depressed by 14% in the hypoglycemic animals, i.e., 61 μmol/100 g/min in hypoglycemia compared to 71 μmol/100 g/min in the normoglycemic controls ( p < 0.05). lCMRglc was lower in 47 of 49 structures examined but statistically significantly below the rate in normoglycemic rats in only six structures ( p < 0.05) by multiple comparison statistics. Regions within the brainstem were most prominently affected. The greatest reductions, statistically significant or not, occurred in structures in which glucose utilization is normally high, suggesting that glucose delivery and transport to the tissue became rate-limiting first in those structures with the greatest metabolic demands for glucose.

scholarly journals Brain Glucose Levels in Portacaval-Shunted Rats with Chronic, Moderate Hyperammonemia: Implications for Determination of Local Cerebral Glucose Utilization

1994 ◽  
Vol 14 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Nancy F. Cruz ◽  
Gerald A. Dienel
Keyword(s):  
Glucose Utilization ◽  
Normal Values ◽  
Brain Structures ◽  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Dg Method ◽  
The Brain

Rates of glucose utilization (lCMRglc) in many structures of the brain of fed, portacaval-shunted rats, when assayed with the [14C]deoxyglucose (DG) method in our laboratory, were previously found to be unchanged (30 of 36 structures) or depressed (6 structures) during the first 4 weeks after shunting, but to rise progressively to higher than normal values in 25 of 36 structures from 4–12 weeks. In contrast, lCMRglc, when assayed with the [14C]glucose method in another laboratory, was depressed in most structures of brains of 4–8-week shunted rats that had relatively high brain ammonia levels. There was a possibility that the increases in lCMRglc obtained with the [14C]DG method may have been artifactual, due, in part, to a change in brain glucose content which could alter the value of the lumped constant of the DG method. Brain glucose levels of shunted rats were, therefore, assayed by both direct chemical measurement in freeze-blown samples and by determination of steady-state brain:plasma distribution ratios for [14C]methylglucose; the methylglucose distribution ratio varies as a function of plasma and tissue glucose contents. Within a week after shunting, ammonia levels in blood and brain rose to 0.25–0.30 m M and 0.35–0.70 μmol/g, respectively, and mean plasma glucose levels fell from 9–10 m M to 7.4–8.5 m M, and then remained nearly constant. Brains of fedshunted rats had normal glycogen levels and stable but moderately reduced glucose contents between 1 and 12 weeks (i.e., 1.9–2.2 μmol/g). [14C]Methylglucose distribution ratios were essentially the same as those in controls in 22 brain structures at 2 and 8 weeks after shunting. Because brain glucose levels remained stable from 1 to 12 weeks after shunting, there is no evidence to support the hypothesis that the value of the lumped constant would have changed and caused an artifactual rise in lCMRglc.

scholarly journals Study on the Adsorption Kinetics of Acid Red 3B on Expanded Graphite

2008 ◽  
Vol 5 (4) ◽  
pp. 802-809 ◽  
Author(s):  
Xiu-yan Pang ◽  
Fei Gong
Keyword(s):  
Activation Energy ◽  
Adsorption Kinetics ◽  
Adsorption Process ◽  
Expanded Graphite ◽  
Chemical Oxidation ◽  
Adsorption Rate ◽  
Order Kinetic ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Expanded graphite (EG) is a kind of important adsorbent for organic compound such as oil and dyes. We have investigated the adsorption kinetics characteristics of this adsorbent for dye. EG was prepared with 50 mesh crude graphite through chemical oxidation intercalation of potassium permanganate and vitriol, and dye of acid red 3B was used as model sorbate. We have studied the adsorption kinetic models and rate-limiting step of the process. Adsorption rate and activation energy of the adsorption process were calculated. Kinetic studies show that the kinetic data are well described by the pseudo second-order kinetic model. The equilibrium adsorbance increases with the increase of the initial acid red 3B concentration. Initial adsorption rate increases with the increase of the initial dye concentration and temperature. Adsorption process of acid red 3B on EG has small activation energy. Internal diffusion appears to be the rate-limiting step for the adsorption process.

Local cerebral glucose utilization in fetal and neonatal sheep

1984 ◽  
Vol 246 (4) ◽  
pp. R608-R618 ◽  
Author(s):  
R. M. Abrams ◽  
M. Ito ◽  
J. E. Frisinger ◽  
C. S. Patlak ◽  
K. D. Pettigrew ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Glucose Utilization ◽  
Average Rate ◽  
Sensory Stimulation ◽  
Mammalian Brain ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Energy Metabolism ◽  
Cerebral Glucose Utilization ◽  
The Brain ◽  
Deoxyglucose Method

The newborn mammalian brain of several species has been shown to have a lower average rate of energy metabolism and a narrower range of rates in its various components than is found in maturity. In a further study of cerebral energy metabolism during development, we have employed the [14C]deoxyglucose method for measuring local cerebral glucose utilization in fetal and neonatal sheep. After establishing the lumped constant to be 0.40 and finding the rate constants for the kinetic behavior of deoxyglucose in plasma and brain to be close to those in other species, we measured the rates of glucose utilization in 44 regions of the brain. The rates were low and homogeneous in midgestation, except for those of brain stem nuclei of the auditory and vestibular systems and those of the hippocampus which were relatively high. In the last 7 wk, local rates rose approximately threefold. After birth there was a further average increase of 50% above full-term levels. The study shows that cerebral energy metabolism rises in most structures during prenatal maturation, a time when sensory stimulation is at a relatively low level and behavioral responses are minimal.

scholarly journals Effects of Insulin on Local Cerebral Glucose Utilization in the Rat

1987 ◽  
Vol 7 (3) ◽  
pp. 309-314 ◽  
Author(s):  
Giovanni Lucignani ◽  
Hiroki Namba ◽  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Steady State ◽  
Glucose Utilization ◽  
Average Rate ◽  
Experimental Period ◽  
Ventromedial Nucleus ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Glucose Utilization ◽  
Hypothalamic Nuclei ◽  
The Brain ◽  
Deoxyglucose Method

The effects of hyperinsulinemia on local cerebral glucose utilization were studied by the quantitative autoradiographic 2-[14C]deoxyglucose method in normal conscious rats under steady-state normoglycemic conditions. Hyperinsulinemia and a steady state of normoglycemia were achieved and maintained during the experimental period by a continuous intravenous (i.v.) infusion of insulin given simultaneously with a programmed i.v. infusion of D-glucose. Hyperinsulinemia under normoglycemic conditions did not change the average rate of glucose utilization in the brain as a whole, but significant increases in local glucose utilization were found selectively in the ventromedial, dorsomedial, and anterior hypothalamic nuclei. The results suggest that a known anatomical pathway linking the dorsomedial and anterior nuclei with the ventromedial nucleus of the hypothalamus may be physiologically activated in response to hyperinsulinemia.

Electrolyte Disorders

2014 ◽  
pp. 578-593
Author(s):  
David B. Mount
Keyword(s):  
Extracellular Ph ◽  
The Body ◽  
Acid Base Balance ◽  
Electrolyte Disorders ◽  
Rate Limiting Step ◽  
Base Balance ◽  
Rate Limiting ◽  
Acid Extrusion ◽  
The Brain ◽  
Oxyhemoglobin Dissociation

The regulation of acid–base balance in the body underlies the importance of pH in a variety of cellular and subcellular biological functions; for example, regulation of protein synthesis and intermediate carbohydrate metabolism are pH-sensitive processes. Clinically, this is apparent by the failure to grow normally in an acidemic environment and explains an increase in anaerobic glycolysis in alkalemia, due to an increase in a rate-limiting step of glycolysis phosphofructokinase-l. pH is important in numerous transport functions across membranes, such as increasing acid extrusion from cells when cellular pH drops. In general, cellular pH is lower than extracellular pH related to the electronegativity within cellular structures. The delivery of oxygen to tissues such as the brain and skeletal muscle is very much dependent on extracellular pH via the shift in the oxyhemoglobin dissociation curve.

scholarly journals Coupled Glucose Transport and Metabolism in Cultured Neuronal Cells: Determination of the Rate-Limiting Step

1995 ◽  
Vol 15 (5) ◽  
pp. 814-826 ◽  
Author(s):  
Richard R. Whitesell ◽  
Michael Ward ◽  
Anthony L. McCall ◽  
Daryl K. Granner ◽  
James M. May
Keyword(s):  
Glucose Transport ◽  
Glucose Utilization ◽  
Neuroblastoma Cell ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting ◽  
Intracellular Glucose

In brain and nerves the phosphorylation of glucose, rather than its transport, is generally considered the major rate-limiting step in metabolism. Since little is known regarding the kinetic coupling between these processes in neuronal tissues, we investigated the transport and phosphorylation of [2-3H]glucose in two neuronal cell models: a stable neuroblastoma cell line (NCB20), and a primary culture of isolated rat dorsal root ganglia cells. When transport and phosphorylation were measured in series, phosphorylation was the limiting step, because intracellular glucose concentrations were the same as those outside of cells, and because the apparent Km for glucose utilization was lower than expected for the transport step. However, the apparent Km was still severalfold higher than the Km of hexokinase I. When [2-3H]glucose efflux and phosphorylation were measured from the same intracellular glucose pool in a parallel assay, rates of glucose efflux were three- to-fivefold greater than rates of phosphorylation. With the parallel assay, we observed that activation of glucose utilization by the sodium channel blocker veratridine caused a selective increase in glucose phosphorylation and was without effect on glucose transport. In contrast to results with glucose, both cell types accumulated 2-deoxy-d-[14C]glucose to concentrations severalfold greater than extracellular concentrations. We conclude from these studies that glucose utilization in neuronal cells is phosphorylation-limited, and that the coupling between transport and phosphorylation depends on the type of hexose used.

scholarly journals Evaluation of Pb (II) Removal from Water Using Sodium Alginate/Hydroxypropyl Cellulose Beads

2020 ◽  
Vol 148 ◽  
pp. 02002 ◽  
Author(s):  
Rodel Guerrero ◽  
Catherine Acibar ◽  
Christine Marie Alarde ◽  
Jane Maslog ◽  
Christine Joy Pacilan
Keyword(s):  
Adsorption Capacity ◽  
Sodium Alginate ◽  
Contact Time ◽  
Hydroxypropyl Cellulose ◽  
Order Kinetic ◽  
Hydrogel Beads ◽  
Rate Limiting Step ◽  
Pseudo Second Order ◽  
Rate Limiting ◽  
Adsorption Kinetic Model

This study examined the removal of Pb2+ ions from aqueous solution with two different lead concentrations using a hydrogel-forming polymer based on hydroxypropyl cellulose (HPC) and sodium alginate (SA). The feasibility of the adsorption behavior of SA/HPC beads has been investigated with three varying ratios of 50:50, 75:25 and 100:0 under a stir condition. The adsorption experiments were done to determine the effects of contact time, lead concentration and SA-HPC ratio to the adsorption capacity of SA-HPC hydrogel beads. The results showed that the ratio 75:25 showed higher adsorption capacity compared to 100:0 and 50:50. It showcased 47.72 mg/g adsorption capacity and 95.45% adsorption percentage after three hours of contact time. The adsorption kinetic model indicated that the adsorption of Pb2+ ions onto the beads followed a pseudo-second order kinetic equation. This means that the adsorption mechanism shows a chemisorption process and its sole rate-limiting step is intraparticle diffusion.

scholarly journals DDRE-22. TARGETING SERINE SYNTHESIS IN BRAIN METASTASIS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i11-i11
Author(s):  
Bryan Ngo ◽  
Eugenie Kim ◽  
Victoria Osorio-Vasquez ◽  
Sophia Doll ◽  
Sophia Bustraan ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Preclinical Models ◽  
Pathway Activity ◽  
Small Molecule Inhibition ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Genetic Suppression ◽  
Phosphoglycerate Dehydrogenase ◽  
Rate Limiting ◽  
The Brain

Abstract The brain environment is low in amino acids, including serine and glycine, both of which are important for tumor growth as they are precursors of proteins and nucleotide bases. How tumor cells overcome these conditions to proliferate and survive in the brain is incompletely understood. Here, we show that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first and rate-limiting step of glucose-derived serine synthesis, enables brain metastasis in multiple human types and in preclinical models. Genetic suppression and small molecule inhibition of PHGDH attenuated brain metastasis, but not extra cranial tumors, and improved the overall survival of mice bearing brain metastasis. These results demonstrate that the tumor nutrient microenvironment determines tumor cell sensitivity to loss of serine synthesis pathway activity and raise the possibility that serine synthesis inhibitors may be useful in the treatment of brain metastases.

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