Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 8432645

An elementary method for implementing complex biokinetic models.

R W Leggett·K F Eckerman·L R Williams
View original source ↗Export metadata ↓

Abstract

Recent efforts to incorporate greater anatomical and physiological realism into biokinetic models have resulted in many cases in mathematically complex formulations that limit routine application of the models. This paper describes an elementary, computer-efficient technique for implementing complex compartmental models, with attention focused primarily on biokinetic models involving time-dependent transfer rates and recycling. The technique applies, in particular, to the physiologically based, age-specific biokinetic models recommended in Publication No. 56 of the International Commission on Radiological Protection, Age-Dependent Doses to Members of the Public from Intake of Radionuclides.

Explore related subjects

Age FactorsAmericiumHumansInfantModels, BiologicalRadiation DosageRadioisotopesSoftwareJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R W Leggett, K F Eckerman, L R Williams. 1993. An elementary method for implementing complex biokinetic models.. https://doi.org/10.1097/00004032-199303000-00004

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1999

Formation of mineralized bone nodules by rat calvarial osteoblasts decreases with donor age due to a reduction in signaling through EP(1) subtype of prostaglandin E(2) receptor.

The effects of prostaglandin E(2) (PGE(2)) on the parameters for proliferation and differentiation were studied in calvarial osteoblast-like cells isolated from rats of various ages. In cells not treated with PGE(2), it was found that mineralized bone nodule (BN) formation, alkaline phosphatase (ALP) activity, and the incorporation rate of [(3)H]thymidine into the cells sharply decreased with the age of the cell donor at 6-50 weeks and then remained at a relatively constant level up to 120 weeks. Before studying the effects of PGE(2) on these parameters, we determined the change in the levels of PGE(2) produced by the untreated cells during the culture period and found that the endogenous PGE(2) reached a maximum on the 4th day of the culture, regardless of the cell donor age, followed by a sharp decrease. The endogenous production was blocked by pretreatment with a cyclooxygenase-2 (COX-2) inhibitor, NS-398, indicating the generation of PGE(2) through a COX-2 pathway. The area of BN was effectively suppressed by NS-398 in the cells from 10- to 35-week-old rats, whereas it was enhanced in the cells from 90- to 120-week-old rats. Treatment with PGE(2 )markedly increased the BN formation and the ALP activity in the cells from 4- to 35-week-old rats (defined as young rats). By contrast, PGE(2) decreased [(3)H]thymidine incorporation into the cells from young rats. The area of BN and the ALP activity decreased significantly, whereas [(3)H]thymidine incorporation into the cells increased by 60-80% in the cells of 80- to 120-week-old rats (defined as aged rats). The stimulatory effects on the cell differentiation and the inhibitory effect on the proliferation in the cells from young rats was mimicked by an EP(1) agonist, 17-phenyl-omega-trinor PGE(2), while an EP(2)/EP(4) agonist, 11-deoxy-PGE(1) and an adenylate cyclase activator, forskolin suppressed the differentiation and enhanced the proliferation regardless of the cell donor age. PGE(2), 11-deoxy-PGE(1) and forskolin, but not 17-phenyl-omega-trinor PGE(2) increased cyclic adenosine monophosphate (cAMP) production. Generation of inositol 1, 4,5-triphosphate (IP(3)) was stimulated by 17-phenyl-omega-trinor PGE(2) or PGE(2), but not by 11-deoxy-PGE(1) or forskolin increased cAMP production in the cells from young rats. By contrast, PGE(2 )had little effect on IP(3 )generation in aged rats. From the overall results, we concluded that PGE(2) exerts stimulatory and inhibitory effects on differentiation through the EP(1)-IP(3) pathway and EP(2)/EP(4)-cAMP pathway, respectively, in the cells from young rats. The EP(1)-IP(3) pathway seems to be inactive in the cells from aged rats.

Age Factors↗
PubMed1999

Plasticity in cerebellar tactile maps in the adult rat.

We previously demonstrated that the fractured tactile cerebellar map within the crus IIa folia of the cerebellar hemispheres reorganizes after deafferentation of the upper lip in neonatal rats (postnatal day [PND] 1-30). The present study examined the capacity of this map to reorganize after deafferentation in adults and animals late in development (PND 30-89). Several months after cauterization of the infraorbital branch of the trigeminal nerve, the tactile map in the granule cell layer of crus IIa reorganized, with representations of intact structures expanding into the denervated area. The pattern of reorganization was similar to reorganization after neonatal lesions in that (1) all representations were from perioral structures, (2) the reorganized map maintained a fractured somatotopy, and (3) the denervated area was predominantly and consistently invaded by the upper incisor representation. We conclude that the spatial pattern of reorganization is essentially the same regardless of the age of deafferentation. However, we also observed developmental differences in reorganization. First, more areas of crus IIa were nonresponsive in animals lesioned later in development (PND 30-89). Second, we found a surprising degree of variability in the pattern of tactilely evoked cerebellar field potentials of PND 30-40 animals compared with neonates and adults, suggesting that this time period differs from other stages. The pattern of evoked potentials reflects the two primary inputs to the map. Our data show that, although both afferent pathways are capable of reorganization throughout development, their relative contribution to the map appears to differ, depending on the age at which lesion occurs.

Age Factors↗
PubMed1999

Optimal weighting systems for direct age-adjustment of vital rates.

Age-adjustment of rates is a basic tool for epidemiologists. The methodologies can be classified into direct and indirect types. The direct methods facilitate a valid comparison between populations or across calendar periods. However, they suffer from the problem of instability. By contrast, the indirect methods achieve maximal precision but may sacrifice a valid inter-populational comparison (violating the 'consistency criteria'). In this paper, we propose a new weighting system to summarize the rates. The weighting system is optimal in the sense that it produces age-adjusted rates which are most stable and ensure a valid comparison between populations. The new weighting system calls for an iterative algorithm. However, the procedure simplifies considerably under some conditions. We use real and simulated data to demonstrate the new method.

Age Factors↗