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A compartmental model for oxygen-carbon dioxide coupled transport in the microcirculation.

We present a multicompartmental model for an oxygen-carbon dioxide transport system. The compartmental equations and their lumped parameters are derived through space averaging of the corresponding distributed model. The model can predict compartmental distributions of oxygen and carbon dioxide partial pressures, oxygen-hemoglobin saturation, and pH. Other unique features include the effects of the radial distribution of partial pressures and the difference in metabolic rates between vessel wall and tissue. A model for the cat brain, based on this formulation, is compared with results of experiments and with two types of earlier models: one without space averaging and one without carbon dioxide transport. The results suggest that space averaging the convective terms significantly affects the behavior of the model. This is consistent with conclusions from our earlier oxygen-only model. Our observations also demonstrate, however, significant differences between the results from the oxygen-carbon dioxide model and the oxygen-only model. For instance, at low blood flow rates or at low level of oxygen input, predicted oxygen partial pressures can differ by as much as 30% between the two models. Results obtained from the present model are supported by available experimental findings.

Animals↗

Ascorbate compartmentalization in the CNS.

Ascorbic acid, found physiologically as the ascorbate anion, is an abundant water-soluble antioxidant. It is concentrated in the intracellular compartment of all tissues in the body. The CNS has particularly high levels of ascorbate. Recent data from this laboratory indicate that ascorbate is distinctly compartmentalized between neurons and glia, with an average intracellular concentration of 10 mM in neurons and 1 mM in glial cells. These data can be contrasted with those for another important low molecular weight antioxidant, glutathione, which is somewhat more concentrated in glia than in neurons. The present review summarizes evidence for ascorbate compartmentalization between neurons and glia and considers these data in light of evidence for the roles of ascorbate as a neuroprotective antioxidant and as a neuromodulator in the CNS.

Journal Article↗

Obstructive uropathy versus nephropathy: compartmental analysis in radioisotopic renography as a new methodology.

A study was carried out to determine the spatial-temporal distribution of the radiopharmaceutical, 99mTc-DTPA in the kidney and its compartments during renography and the use of compartmental analysis to improve the diagnostic capability of renography. A total of 60 individuals formed three groups: group A consisted of 30 normals taken as controls, group B consisted of 15 patients with unilateral nephropathy, and group C consisted of 15 patients with unilateral obstructive uropathy. This retrospective study was performed by processing of the frames acquired in the various stages of renography and determination of the time distribution of radioactivity in the aorta, the renal parenchyma and the renal pelvis. The data acquired were used to produce three curves instead of one for each kidney and to study renal function as a system of six compartments (aorta, left and right renal parenchyma, left and right renal pelvis, and bladder). In all the above compartments the differences among the three groups were significant and were quantified using the flow coefficients of the aortorenal compartments. The differences between the aortic flow coefficients (k1) were statistically significant not only between normal controls and patients, but also between individuals with parenchymatic dysfunction and patients with pelvocalyceal obstruction. The same differences were seen comparing the pelvocalyceal coefficients (k3) of all three groups. The parenchymatic coefficient (k2) presented statistically significant differences between normals and patients which were not observed between the two groups of patients (B and C). Compartmental analysis thus increases the sensitivity of renography, is objective by utilizing quantitative parameters, enables the separate analysis of the functional behavior of the various renal compartments, and improves the differential diagnosis between parenchymatic dysfunction and pelvocalyceal obstruction.

Adolescent↗

Lower extremity compartmental anatomy: clinical relevance to radiologists.

A thorough understanding of compartmental anatomy is necessary for the radiologist participating in the care of a patient with a lower extremity musculoskeletal malignancy. Localization of tumor to compartment of origin and identification of extracompartmental spread preoperatively are needed to correctly stage a tumor and determine the appropriate surgical management. An understanding of the locations of fascial boundaries, extracompartmental tissues, and neurovascular structures of the thigh and lower leg facilitates this diagnostic process. For the radiologist planning to biopsy a suspicious musculoskeletal lesion, consultation with the referring orthopaedic surgeon is recommended in order to jointly select an appropriate percutaneous biopsy approach. Adequate preprocedural planning ensures selection of an approach which prevents iatrogenic tumor spread beyond the compartment of origin, protects neurovascular structures, and allows complete resection of the biopsy tract and scar at the time of surgical resection without jeopardizing a potential limb-sparing procedure. Cross-sectional anatomic review and case examples demonstrate the importance of a detailed understanding of compartmental anatomy when approaching the patient with a lower extremity musculoskeletal tumor.

Adult↗

Effect of scatter correction on the compartmental measurement of striatal and extrastriatal dopamine D2 receptors using [123I]epidepride SPET.

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D(2) receptors using [(123)I]epidepride. Eight healthy human subjects [age 30+/-8 (range 22-46) years] participated in a study with a bolus injection of 373+/-12 (354-389) MBq [(123)I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry micro (SC) and without scatter correction using broad-beam micro (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [(18)F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.

Adult↗

Surface adsorption, intracellular accumulation and compartmentalization of Pb(II) in batch-operated lagoons with Salvinia minima as affected by environmental conditions, EDTA and nutrients.

The effects of environmental factors and nutrients on the various possible removal mechanisms (surface adsorption, intracellular accumulation and precipitation to sediments) and partitioning of lead among various compartments (plant biomass, water column and sediments) in Salvinia minima batch-operated lagoons, were evaluated. Surface adsorption was found to be the predominant mechanism for Pb(II) removal under all environmental conditions tested in the absence of nutrients (an average of 54.3%) and in a nutrient medium (modified Hutner 1/10 medium) free of EDTA and phosphates (54.41%) at "high" initial Pb(II) concentrations (in the range of 10.3+/-0.13 to 15.2+/-0.05 mg/L). Under these conditions, the bioconcentration factors (BCFs) were 2,431+/-276 and 2,065+/-35, respectively. Lead removal was very rapid during the first 4 h and reached 70% in the absence of nutrients at the "medium" light intensity and temperature (LIT) tested, 88% in nutrient medium free of EDTA and supplemented with synthetic wastewater (at the "lowest" LIT tested), and 85% in medium free of EDTA and phosphates. It was concluded that the mechanisms of lead removal by S. minima, and the compartmentalization of this metal in the microcosm of batch-operated lagoons, are primarily a function of the presence of certain nutrients and chelants, with secondary dependence on environmental conditions. In addition, the results indicate that the percentage of lead removed is only a gross parameter and that the complementary use of BCF and compartmentalization analysis is required to gain a full insight into the metal removal process.

Adsorption↗

Area/moment and compartmental modeling of pharmacokinetics during pregnancy: applications to maternal/fetal exposures to corticosteroids in sheep and rats.

PURPOSE: The pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed. METHODS: Betamethasone in the maternal/fetal circulations of sheep was measured by HPLC after maternal intramuscular injection (n = 4) of 170 microg kg(-1) of a depot formulation. Additional data for beta-methasone in sheep and dexamethasone pharmacokinetics in rats were obtained from the literature. Area/Moment equations were derived using mass balance concepts, statistical moments, and Laplace theory. Area/Moment analysis, compartmental modeling, and allometric scaling to man for betamethasone were performed using WinNonlin and ADAPT II programs. RESULTS: Polyexponential maternal/fetal profiles for corticosteroids were observed. Clearance terms for corticosteroid transfer from fetus to mother were 4-fold higher than the clearance term for transfer in the opposite direction. A placental efflux process may restrict fetal access of corticosteroids which are known PGP substrates. The elimination clearance estimates indicate that fetal metabolism plays a minor role in corticosteroid elimination. CONCLUSIONS: Generalized and specific models for maternal/fetal pharmacokinetics were developed. An efflux transport mechanism, such as the known placental expression of PGP, could explain the limited fetal exposure of corticosteroids.

Animals↗

Management of compartmental syndrome. Diagnostic and surgical considerations.

Compartmental syndrome is a condition in which swelling within a closed anatomic space increases the intracompartmental pressure to compromise the circulation and function of tissue within that space. Unless this condition is recognized early and treated by prompt surgical decompression, permanent neuromuscular deficits may result. In those instances in which early clinical evidence of this syndrome is difficult to assess, monitoring of intramuscular pressures may be valuable adjunct in the clinical evaluation of patients at risk for this syndrome. The association of compartmental syndrome with a wide variety of circumstances and the importance of an early diagnosis make it essential that all physicians be familiar with this condition. As physician awareness and recognition of this condition increase, the complications associated with it can be greatly reduced.

Adult↗

Transfer function matrix of a compartmental model. A program for the rapid writing of its symbolic expression.

A method for the fast writing of the symbolic expression of the transfer function matrix of a compartmental model has been implemented on a FORTRAN G program. Special care has been devoted to the reduction of computations and memory by means of original subroutines. The program input is very simple and the output very clear to general users. The program may be employed for the study of all input-output relations of he considered compartmental model. Details on the computational methods adopted for its implementation are given. Application examples are reported.

Computers↗

Applications of a general method for deconvolution using compartmental analysis.

A method of deconvolution is illustrated using compartmental models. The approach can be used to determine an arbitrary unknown input function from a measured response and the impulse response of the system. Compartmental models are constructed to specify (a) the function fitting the response data and (b) the impulse response of the system. Simulation of these models is then used to construct the unknown input function.

Alanine↗

Transient biochemical compartmentalization of Purkinje cells during early cerebellar development.

It has recently been observed that during early cerebellar development--from embryonic Day 17 to postnatal Day 3 in the rat--only certain discrete clusters of Purkinje cells (PCs) are immunoreactive to cyclic GMP-dependent protein kinase (cGK). In contrast, at later stages and in the adult, all the PCs are immunoreactive. These results obtained with cGK suggest a transitory intrinsic heterogeneity in the immature cerebellar cortex. It seemed therefore interesting to investigate the distribution of other PC markers during early development in the rat and in other species. The results presented here were obtained with two other antibodies--against vitamin D-dependent calcium binding protein and against Purkinje cell specific glycoprotein--which, like cGK, label all adult PCs. Each antibody gave a different and reproducible mosaic of positive and negative clusters of PCs in the perinatal cerebellum, thus indicating a transient biochemical compartmentalization resulting from the differential expression of parts of the same genotype by clusters of PCs. This compartmentalization in concomitant with the ingrowing of the cerebellar afferents. Once synaptogenesis starts, the biochemical heterogeneity of PCs disappears.

Animals↗

Parallel development of noradrenergic innervation and cellular compartmentation in the rat spleen.

By combining neurochemical measurement of norepinephrine (NE) with double-label immunocytochemistry for tyrosine hydroxylase-positive (TH+) noradrenergic nerves and specific lymphoid markers, we have examined the developmental compartmentation of noradrenergic nerves in the rat spleen. TH+ nerve fibers were present in the white pulp of the spleen at birth, among surface IgM-positive (sIgM+) B lymphocytes at the outer border of the periarteriolar lymphatic sheath (PALS), distant from the central artery. During the first 7 days, noradrenergic innervation developed rapidly, forming plexuses of nerve fibers along the central artery and its branches, among T and B lymphocytes of the PALS, and along the developing marginal sinus where ED3+ macrophages accumulate. The splenic concentration of NE (per mg wet wt.) and 3-methoxy-4-hydroxy-phenetheleneglycol (MHPG), a NE metabolite, increased rapidly during this period, suggesting that NE is available and released from these nerves. From 7-14 days, the white pulp expanded to include an inner PALS, outer PALS, marginal sinus, and marginal zone; during this period, TH+ fibers arborized principally among T lymphocytes of the inner PALS and adjacent to macrophages along the marginal sinus. By 14 days of age, NE concentration reached adult levels, although the MHPG/NE ratio (an index of NE turnover) remained higher throughout development than in adulthood. Finally, from 14-28 days, the outer PALS expanded to include follicles containing sIgM+ B lymphocytes. At the earliest stages of follicular development, a parafollicular rim of noradrenergic fibers was present, providing occasional branches which arborized within the follicle. No further changes were observed in either noradrenergic innervation or cellular compartmentation after 28 days of age. These findings suggest that noradrenergic fibers are present in developing compartments of the spleen at the earliest stages of their development, providing norepinephrine for interaction with a variety of adrenoceptor-bearing lymphoid and nonlymphoid cells.

Animals↗

Subcellular compartmentalization of cAMP-dependent protein kinase regulatory subunits during palate ontogeny.

Mammalian palatal ontogeny involves epithelial-mesenchymal interactions, cell differentiation, and cell movements. These events occur on days 12, 13, and 14 of gestation in the C57BL/6J mouse embryo. During this period intracellular cAMP levels and cAMP-dependent protein kinase (cAMP-dPK) levels in the palate transiently elevate. Cyclic AMP activates cAMP-dPK by binding primarily to two types of regulatory subunits of this enzyme, designated as RI and RII. To assess whether differential compartmentalization of the regulatory subunits occurs during palatal ontogeny, cytosolic, nuclear, and particulate fractions were prepared from day 12, 13, and 14 embryonic maxillary and palatal tissue. After photo-affinity labeling of each fraction with 8-azido [32P] cAMP, SDS-PAGE, and autoradiography, autoradiograms were analyzed densitometrically. The RI isoform predominated in the nuclear and particulate fractions on all three developmental days; whereas RII predominated in the cytosolic fractions. Thus, differential compartmentalization of cAMP-dPK may be a means by which cAMP dependent responses are regulated during palatogenesis.

Affinity Labels↗

Equilibrium points for nonlinear compartmental models.

Equilibrium points for nonlinear autonomous compartmental models with constant input are discussed. Upper and lower bounds for the steady states are derived. Theorems guaranteeing existence and uniqueness of equilibrium points for a large collection of system are proved. New information relating to mean residence times is developed. Asymptotic results and a section on stability are included. A recursive process is discussed that generates iterates that converge to steady states for certain types of models. An interesting range of models are included as examples. An attempt is made to provide general qualitative theory for such nonlinear compartmental systems.

Acquired Immunodeficiency Syndrome↗

Domain of validity of classical models of leucine metabolism assessed by compartmental modeling.

Whole-body modeling of in vivo leucine (an essential amino acid) metabolism is fundamentally difficult due to the complexity of the system. This has favored the use of two simple kinetic models, the so-called primary and reciprocal pool models, to interpret tracer data, but their domain of validity is uncertain. We define here the error of these two approaches by using comprehensive compartmental models of leucine metabolism as true representations of the leucine system. Of particular interest is the comparison of the two simple models with an 11-compartment model characterized by a rich intracellular compartmentation that has recently been proposed as a sound physiological description of the system. Formulas are derived that define in structural terms the error of the primary and reciprocal pool models.

Humans↗

Stochastic compartmental models with Prendville growth mechanisms.

We consider a stochastic compartmental model in which cells reproduce in accordance with a regulated birth and death process. We find expressions for the mean vector and covariance matrix for the number of cells in these compartments. We obtain the asymptotic behavior of the mean vector in the general case and explicit expressions for two compartmental and mammillary systems.

Animals↗

Compartmental models and competing risk.

General compartmental models are derived using competing risk arguments. When the risk variables are exponential, the results specialize to the standard stationary Markov compartmental model. Iterative methods of solving the fundamental integral equation are given, and the uniqueness of the solution is incidentally established. The analysis is extended to include fixed inputs, orderly and nonorderly stream infusions, and time dependency. The study is motivated by a biological system that evolves through various stages over time.

Biological Evolution↗

A model for determination of total body protein synthesis based upon compartmental analysis of the plasma [15N] glycine decay curve.

A model for whole body glycine nitrogen flux based on the compartmental analysis of plasma [15N] glycine decay curves is described and used for the measurements of (1) total body glycine nitrogen flux and the components of this flux in three healthy young adults and (2) total body protein synthesis based on the conversion of 15N to excretory products, ie, the sum of urinary [15N] urea and 15NH3 and the amount of labeled urea remaining in the body at five hours following administration of [15N] glycine. The mean glycine nitrogen flux was 3.93 +/- 0.42 mg N X kg-1 X h-1 (SEM). The major components of this flux are de novo synthesis of glycine, which accounts for 18% to 27%, and release from protein breakdown, which accounts for 62% to 73%. The outward pathways of glycine from the total body free glycine pool are conversion to other amino acids and oxidation to excretory end products (30% to 42%) and incorporation into protein, which accounts for 45% to 61% of glycine N loss from the metabolic pool. The mean rate of total body protein synthesis as determined by compartmental analysis was 3.56 g protein X kg-1 X day-1. The results that were obtained for protein synthesis and whole body glycine kinetics accord well with previous studies in normal adults, using the stochastic model.

Adult↗