scholarly journals Distribution and Elimination of Ingested Mercuric Oxide in Mice

1983 ◽  
Vol 2 (4) ◽  
pp. 307-317
Author(s):  
G. G. Berg ◽  
B. S. Smith
Keyword(s):  
Body Burden ◽  
Compartment Model ◽  
Whole Body ◽  
Published Data ◽  
Mercuric Oxide ◽  
Half Time ◽  
The Brain ◽  
Intermediate Rate ◽  
Body Concentration ◽  
Concentration Ratios

Neutron-activated mercuric oxide was administered by gavage to female BALB/c mice. Counts of 197Hg and 203Hg in the whole body, urine, and feces were followed for up to 36 days. Elimination of mercury fitted a 3-compartment model. Nonpregnant mice eliminated approximately 87.5% of the dose at a fast rate (t1-2 = 9 hours), 12% at an intermediate rate (t>1/2 = 2 days), and 0.5% at a slow rate (t1/2 = 15 days). Each half-time was approximately 7 times shorter than the corresponding half-time fitted to published data on rats. Mice were also faster than humans in eliminating the ingested mercury. Pregnancy slowed down the intermediate rate of elimination. The total administered dose was recovered from feces and urine in a 9:1 ratio. Organ weights and mercury burdens were measured after serial sacrifice. Peak concentrations were reached within two days, with highest levels in kidneys followed by placentae and livers. In brains, peak concentrations were delayed and low. Subsequent losses of mercury differed widely in rate constants, with fastest overall rates in the brain, intestine, and integument, followed in order by whole body, liver, and kidneys. Ten days after dosing, mercury concentration ratios of placenta to 17-day old fetus were 20:1; 11 days after dosing, and with less than 2% of body burden remaining, while body concentration ratios of mother to neonate were 4:1. The data indicated that mice eliminated mercuric salts faster than had been reported for rats or humans, and that rapid elimination coupled with a placental barrier shielded fetuses from equlibrating with the peak concentrations of mercury found in dams after a single dose.

Metallic prions

2004 ◽  
Vol 71 ◽  
pp. 193-202 ◽  
Author(s):  
David R Brown
Keyword(s):  
Prion Protein ◽  
Binding Capacity ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Published Data ◽  
Normal Brain ◽  
Copper Binding ◽  
Loss Of Function ◽  
Spongiform Encephalopathies ◽  
The Brain

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. To this end much work has focused on elucidation of the normal function and activity of PrPc. Substantial evidence supports the notion that PrPc is a copper-binding protein. In conversion to the abnormal isoform, this Cu-binding activity is lost. Instead, there are some suggestions that the protein might bind other metals such as Mn or Zn. PrPc functions currently under investigation include the possibility that the protein is involved in signal transduction, cell adhesion, Cu transport and resistance to oxidative stress. Of these possibilities, only a role in Cu transport and its action as an antioxidant take into consideration PrPc's Cu-binding capacity. There are also more published data supporting these two functions. There is strong evidence that during the course of prion disease, there is a loss of function of the prion protein. This manifests as a change in metal balance in the brain and other organs and substantial oxidative damage throughout the brain. Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies.

scholarly journals Has molecular imaging delivered to drug development?

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170112 ◽  
Author(s):  
Philip S. Murphy ◽  
Neel Patel ◽  
Timothy J. McCarthy
Keyword(s):  
Molecular Imaging ◽  
Drug Development ◽  
Clinical Studies ◽  
Pharmaceutical Research ◽  
Whole Body ◽  
Drug Candidate ◽  
Clinical Drug Development ◽  
Target Binding ◽  
The Brain ◽  
Clinical Drug

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

scholarly journals Individual whole-body concentration of 137Cesium is associated with decreased blood counts in children in the Chernobyl-contaminated areas, Ukraine, 2008–2010

2013 ◽  
Vol 25 (3) ◽  
pp. 334-342 ◽  
Author(s):  
Anna Lindgren ◽  
Eugenia Stepanova ◽  
Vitaliy Vdovenko ◽  
Daria McMahon ◽  
Oksana Litvinetz ◽  
...  
Keyword(s):  
Whole Body ◽  
Body Concentration

Whole-body to tissue concentration ratios for use in biota dose assessments for animals

2010 ◽  
Vol 49 (4) ◽  
pp. 549-565 ◽  
Author(s):  
Tamara L. Yankovich ◽  
Nicholas A. Beresford ◽  
Michael D. Wood ◽  
Tasuo Aono ◽  
Pål Andersson ◽  
...  
Keyword(s):  
Tissue Concentration ◽  
Whole Body ◽  
Dose Assessments ◽  
Concentration Ratios

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

scholarly journals Application of standards and models in body composition analysis

2015 ◽  
Vol 75 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Manfred J. Müller ◽  
Wiebke Braun ◽  
Maryam Pourhassan ◽  
Corinna Geisler ◽  
Anja Bosy-Westphal
Keyword(s):  
Body Composition ◽  
Clinical Decision Making ◽  
Compartment Model ◽  
Clinical Decision ◽  
Whole Body ◽  
Composition Analysis ◽  
Body Composition Analysis ◽  
Physical Functions ◽  
Body Components

The aim of this review is to extend present concepts of body composition and to integrate it into physiology. In vivo body composition analysis (BCA) has a sound theoretical and methodological basis. Present methods used for BCA are reliable and valid. Individual data on body components, organs and tissues are included into different models, e.g. a 2-, 3-, 4- or multi-component model. Today the so-called 4-compartment model as well as whole body MRI (or computed tomography) scans are considered as gold standards of BCA. In practice the use of the appropriate method depends on the question of interest and the accuracy needed to address it. Body composition data are descriptive and used for normative analyses (e.g. generating normal values, centiles and cut offs). Advanced models of BCA go beyond description and normative approaches. The concept of functional body composition (FBC) takes into account the relationships between individual body components, organs and tissues and related metabolic and physical functions. FBC can be further extended to the model of healthy body composition (HBC) based on horizontal (i.e. structural) and vertical (e.g. metabolism and its neuroendocrine control) relationships between individual components as well as between component and body functions using mathematical modelling with a hierarchical multi-level multi-scale approach at the software level. HBC integrates into whole body systems of cardiovascular, respiratory, hepatic and renal functions. To conclude BCA is a prerequisite for detailed phenotyping of individuals providing a sound basis for in depth biomedical research and clinical decision making.

Low positive yield from routine inclusion of the brain in whole-body 18F-FDG PET/CT imaging for noncerebral malignancies

2013 ◽  
Vol 34 (6) ◽  
pp. 540-543 ◽  
Author(s):  
Kuruva Manohar ◽  
Anish Bhattacharya ◽  
Bhagwant R. Mittal
Keyword(s):  
Fdg Pet ◽  
Ct Imaging ◽  
Whole Body ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
The Brain

Whole-body adaptation to novel dynamics does not transfer between effectors

2021 ◽  
Author(s):  
Alison Pienciak-Siewert ◽  
Alaa A Ahmed
Keyword(s):  
Postural Control ◽  
Arm Movement ◽  
Movement Planning ◽  
Reaching Movements ◽  
Whole Body ◽  
Postural Control System ◽  
Movement Dynamics ◽  
Gradual Introduction ◽  
Postural Movement ◽  
The Brain

How does the brain coordinate concurrent adaptation of arm movements and standing posture? From previous studies, the postural control system can use information about previously adapted arm movement dynamics to plan appropriate postural control; however, it is unclear whether postural control can be adapted and controlled independently of arm control. The present study addresses that question. Subjects practiced planar reaching movements while standing and grasping the handle of a robotic arm, which generated a force field to create novel perturbations. Subjects were divided into two groups, for which perturbations were introduced in either an abrupt or gradual manner. All subjects adapted to the perturbations while reaching with their dominant (right) arm, then switched to reaching with their non-dominant (left) arm. Previous studies of seated reaching movements showed that abrupt perturbation introduction led to transfer of learning between arms, but gradual introduction did not. Interestingly, in this study neither group showed evidence of transferring adapted control of arm or posture between arms. These results suggest primarily that adapted postural control cannot be transferred independently of arm control in this task paradigm. In other words, whole-body postural movement planning related to a concurrent arm task is dependent on information about arm dynamics. Finally, we found that subjects were able to adapt to the gradual perturbation while experiencing very small errors, suggesting that both error size and consistency play a role in driving motor adaptation.

scholarly journals Quantification of the whole-body burden of radiographic osteoarthritis using factor analysis

2011 ◽  
Vol 13 (5) ◽  
pp. R176 ◽  
Author(s):  
Amanda E Nelson ◽  
Robert F DeVellis ◽  
Jordan B Renner ◽  
Todd A Schwartz ◽  
Philip G Conaghan ◽  
...  
Keyword(s):  
Factor Analysis ◽  
Body Burden ◽  
Whole Body ◽  
Radiographic Osteoarthritis

Insulin resistance is localized to skeletal but not heart muscle in type 1 diabetes

1993 ◽  
Vol 264 (5) ◽  
pp. E756-E762 ◽  
Author(s):  
P. Nuutila ◽  
J. Knuuti ◽  
U. Ruotsalainen ◽  
V. A. Koivisto ◽  
E. Eronen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Compartment Model ◽  
Normal Subjects ◽  
Whole Body ◽  
Diabetic Patients ◽  
Uptake Rates ◽  
Arm Muscles ◽  
Type 1 Diabetic Patients

To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897–916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

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