scholarly journals Cerebral Blood Flow with the Continuous Infusion of Oxygen-15-Labeled Water

1985 ◽  
Vol 5 (4) ◽  
pp. 566-575 ◽  
Author(s):  
S. C. Jones ◽  
J. H. Greenberg ◽  
R. Dann ◽  
G. D. Robinson ◽  
M. Kushner ◽  
...  
Keyword(s):  
White Matter ◽  
Continuous Infusion ◽  
Human Subjects ◽  
Recovery Coefficient ◽  
Whole Brain ◽  
Positron Emission ◽  
Arterial Concentration ◽  
Normal Human

This work describes the determination of CBF in eight normal human subjects with positron emission tomographic (PET) imaging using the continuous intravenous infusion of H215O. A whole-brain CBF model is described that permits the comparison of the CBF values determined using PET with those obtained using other methods. This model includes a correction for whole-brain recovery coefficient, a correction for the underestimation of flow due to the nonlinearity of the CBF model when considering tissue that includes both gray and white matter, the use of in vitro-determined brain–blood partition coefficients for gray and white matter, and a variation of the equilibrium model that permits the arterial concentration to vary. CBF values using this method compare well with values determined previously. Regional determinations using a brain overlay atlas are presented. Radiation dosimetry for the continuous infusion of H215O is also included.

scholarly journals A systematic review of the neurobiological aspects of memory in the aging process

2011 ◽  
Vol 5 (4) ◽  
pp. 310-321
Author(s):  
Eduardo Moreira de Oliveira ◽  
Priscilla Tiemi Kissaki ◽  
Tiago Nascimento Ordonez ◽  
Thaís Bento Lima-Silva
Keyword(s):  
Systematic Review ◽  
Aging Process ◽  
Human Subjects ◽  
Basic Research ◽  
Brain Regions ◽  
Morphological Alterations ◽  
Search Terms ◽  
Processing Information ◽  
Normal Human

Abstract A systematic review of the neuroanatomical literature was performed to determine the neuropharmacological aspects most relevant to the study of memory processes. Articles were retrieved using the search terms "biology of memory", "memory and aging", "memory impairment", "elderly and memory," and their equivalents in Portuguese. Of the studies surveyed, five studies dealt with epidemiological and demographic issues, 12 were clinical trials i.e. were based on testing and implementation of instruments in human subjects, 33 studies were basic research involving studies of mice, rats and non-human primates, and biochemical and in vitro trials and finally, 52 studies were literature reviews or book chapters which in our view, fell into this category. Conclusions: The work sought to highlight which neural networks are most involved in processing information, as well as their location within brain regions and the way in which neurotransmitters interact with each other for the formation of these memories. Moreover, it was shown how memory changes during the normal human aging process, both positively and negatively, by analyzing the morphological alterations that occur in the brain of aging individuals.

scholarly journals Reproducibility of Cerebral Glucose Metabolic Measurements in Resting Human Subjects

1988 ◽  
Vol 8 (4) ◽  
pp. 502-512 ◽  
Author(s):  
Elsa J. Bartlett ◽  
Jonathan D. Brodie ◽  
Alfred P. Wolf ◽  
David R. Christman ◽  
Eugene Laska ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Brain Metabolism ◽  
Human Subjects ◽  
Normal Subjects ◽  
Time Of Day ◽  
Cerebral Glucose Metabolism ◽  
Whole Brain ◽  
Positron Emission ◽  
Subcortical Regions ◽  
Regional Cerebral Glucose Metabolism

Positron emission tomography with 11C-2-deoxyglucose was used to determine the test-retest variability of regional cerebral glucose metabolism in 22 young normal right-handed men scanned twice in a 24-h period under baseline (resting) conditions. To assess the effects of scan order and time of day on variability, 12 subjects were scanned in the morning and afternoon of the same day (a.m.-p.m.) and 10 in the reverse order (p.m.-a.m.) with a night in between. The effect of anxiety on metabolism was also assessed. Seventy-three percent of the total subject group showed changes in whole brain metabolism from the first to the second measurement of 10% or less, with comparable changes in various cortical and subcortical regions. When a scaling factor was used to equate the whole brain metabolism in the two scans for each individual, the resulting average regional changes for each group were no mote than 1%. This suggests that the proportion of the whole brain metabolism utilized regionally is stable in a group of subjects over time. Both groups of subjects had lower morning than afternoon metabolism, but the differences were slight in the p.m.-a.m. group. One measure of anxiety (pulse at fun 1) was correlated with run 1 metabolism and with the percentage of change from run 1 to run 2. No significant run 2 correlations were observed. This is the first study to measure test-retest variability in cerebral glucose metabolism in a large sample of young normal subjects. It demonstrates that the deoxyglucose method yields low Intrasubject variability and high stability over a 24-h period.

scholarly journals Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746

2016 ◽  
Vol 37 (3) ◽  
pp. 1095-1107 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Beata Planeta ◽  
Nabeel Nabulsi ◽  
Donna Palumbo ◽  
Xiaoxi Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Human Subjects ◽  
Receptor Occupancy ◽  
Healthy Human ◽  
Positron Emission ◽  
Relationship Of ◽  
The Relationship ◽  
Pet Scans

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds “tracer” levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [11C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [11C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%–97% and 30%–93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%–15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

scholarly journals Determination of activity of antioxidants in human subjects

1999 ◽  
Vol 58 (4) ◽  
pp. 1015-1024 ◽  
Author(s):  
Garry G. Duthie
Keyword(s):  
Oxidative Stress ◽  
Human Subjects ◽  
Control Schemes ◽  
Total Antioxidant ◽  
Plasma Measurements ◽  
Determination Of Activity ◽  
Nutritional Antioxidants

Evidence from biochemical and animal models suggests that nutritional antioxidants should inhibit the development of diseases such as CHD and certain cancers. This evidence is not clearly corroborated by intervention studies in human subjects, due, in part, to inadequacies in current analytical methodologies. Althoughin vitroassays can give useful information on the attributes required by a compound to act as an antioxidant, results may have little nutritional relevance due to limited bioavailability. The determination of antioxidants in blood is often used as a measure of antioxidant statusin vivo, but may not necessarily reflect concentrations in target tissues where oxidative stress is greatest. In addition, the accumulation of antioxidants in selective tissues may not be apparent from plasma measurements. Participation in quality-control schemes for antioxidant determination by HPLC allows inter-laboratory comparison of results. Moderation of indices of oxidative damage to lipids, proteins and DNA can provide information on the effectiveness of compounds as nutritional antioxidants. However, most current methods of assessing oxidative stress are subject to confounding factors of non-oxidative origin. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. They give different results, should never be used in isolation, and results should be interpreted with caution. Until more is known about the activity and metabolic fate of antioxidants, caution should be exercised in the consumption of large amounts of commercially-available antioxidant preparations.

scholarly journals Quantification of Neuroreceptors in the Living Human Brain. II. Inhibition Studies of Receptor Density and Affinity

1986 ◽  
Vol 6 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Dean F. Wong ◽  
Albert Gjedde ◽  
Henry N. Wagner ◽  
Robert F. Dannals ◽  
Kenneth H. Douglass ◽  
...  
Keyword(s):  
Human Brain ◽  
Blocking Agent ◽  
Receptor Density ◽  
Positron Emission ◽  
Tracer Accumulation ◽  
Inhibition Studies ◽  
Human Autopsy Material ◽  
Human Autopsy

A method for estimating receptor density ( Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3- N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g−1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 n M by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.

Determination of contact sensitization potential of chemicals using in vitro reconstructed normal human epidermal model EpiDerm: Impact of the modality of application

2016 ◽  
Vol 258 ◽  
pp. S230
Author(s):  
S. Letasiova ◽  
E. Corsini ◽  
V. Galbiati ◽  
H. Kandarova ◽  
D. Lehmeier ◽  
...  
Keyword(s):  
Contact Sensitization ◽  
Normal Human

The Determination of Triglycerides in Plasma and Tissues

1968 ◽  
Vol 14 (2) ◽  
pp. 156-161 ◽  
Author(s):  
Vishwanath M Sardesai ◽  
Joan A Manning
Keyword(s):  
Human Subjects ◽  
Plasma Samples ◽  
Simple Method ◽  
Glycerol Moiety ◽  
Normal Human ◽  
Time Required ◽  
Colored Compound

Abstract A simple method for the determination of plasma and tissue triglycerides is described. This procedure involves the extraction and saponification of triglycerides, the oxidation of the glycerol moiety to formaldehyde, and the conversion of formaldehyde to a yellow-colored compound, 3,5 diacetyl-1-4 dihydrolulidine, the intensity of which is determined spectrophotometrically. The recoveries of triglycerides added to plasma and tissues have been satisfactory. Plasma samples obtained from normal human subjects are found to have triglycerides in the range 83-200 mg./100 ml. From the standpoint of sensitivity, simplicity, and time required, this technic is believed to be an improvement over previously described procedures for triglyceride determination.

Determination of Unbound Bilirubin in the Serum of Newborns

1974 ◽  
Vol 20 (7) ◽  
pp. 783-789 ◽  
Author(s):  
Jorgen Jacobsen ◽  
Richard P Wennberg
Keyword(s):  
Binding Capacity ◽  
Newborn Infants ◽  
Albumin Binding ◽  
Initial Oxidation ◽  
High Affinity ◽  
Normal Human ◽  
Unbound Bilirubin ◽  
Rate Limiting

Abstract An enzymatic assay is described for non-albuminbound bilirubin in the serum of newborn infants. Unbound bilirubin is oxidized to colorless compounds by ethyl hydroperoxide in the presence of horseradish peroxidase (EC 1.11.1.7), while albumin-bound bilirubin is protected from oxidation. Because the equilibrium between albumin and bilirubin occurs rapidly, the oxidation step is rate limiting, and the initial oxidation velocity of total bilirubin is proportional to the unbound bilirubin concentration. By titrating serum with bilirubin in vitro, the association constant and binding capacity of high-affinity sites for albumin binding can be determined. Normal human serum albumin tightly binds 1 mole of bilirubin per mole of albumin (binding constant, 2-4 x 108 liter/mol). Although weaker secondary binding occurs, the unbound bilirubin fraction increases rapidly after the high-affinity binding sites are saturated. Compromised newborns may have a decreased apparent binding capacity and (or) binding affinity. The method can be used to assess the risk of a jaundiced infant for bilirubin encephalopathy.

scholarly journals Diclofenac and Its Acyl Glucuronide: Determination of In Vivo Exposure in Human Subjects and Characterization as Human Drug Transporter Substrates In Vitro

2015 ◽  
Vol 44 (3) ◽  
pp. 320-328 ◽  
Author(s):  
Y. Zhang ◽  
Y.-H. Han ◽  
S. P. Putluru ◽  
M. K. Matta ◽  
P. Kole ◽  
...  
Keyword(s):  
Human Subjects ◽  
Drug Transporter ◽  
Acyl Glucuronide

scholarly journals Measurement of Regional Cerebral pH in Human Subjects Using Continuous Inhalation of 11CO2 and Positron Emission Tomography

1984 ◽  
Vol 4 (3) ◽  
pp. 458-465 ◽  
Author(s):  
David J. Brooks ◽  
Adriaan A. Lammertsma ◽  
Ronald P. Beaney ◽  
Klaus L. Leenders ◽  
Peter D. Buckingham ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Subjects ◽  
Compartment Model ◽  
Emission Tomography ◽  
Inhalation Technique ◽  
Positron Emission ◽  
Brain Ph ◽  
Normal Human ◽  
Uptake Data ◽  
Arterial Plasma

The cerebral pH of four normal human subjects has been measured using continuous inhalation of 11CO2 and positron emission tomography (PET). 11CO2 was administered to each subject at a constant rate for 15 min, during which time serial arterial plasma 11C levels were determined and serial 11C cerebral uptake PET scans were performed at a fixed axial tomographic level. 11C uptake kinetics were analysed using a three-compartment model. Rate constants have been estimated for the free exchange of 11CO2 between plasma and cerebral compartments for each subject, and their cerebral pH calculated. Whole brain pH values ranged from 6.96 to 7.05, and no significant pH difference between regions containing predominantly grey or white matter was noted. Best fits to 11C uptake data were achieved by effectively neglecting the metabolic fixation of 11C by cerebral tissue. The purpose of this study was to test the feasibility of pH measurement using the 11CO2 continuous inhalation technique. It is concluded from the results and the error analysis that continuous 11CO2 inhalation combined with PET is potentially a simple and useful method for determining regional cerebral pH.

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