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PubMed2005

Compartmental pressure in adults with tibial fracture.

Acute compartment syndrome is associated with tibial fractures and failure to diagnose it leads to grave consequences. This study was conceived with the aim of determining the intra-compartmental pressure in adults with closed tibial fractures and intended to provide early diagnosis of acute compartment syndrome. The Whitesides injection method was used, using hospital [corrected] available materials. The intra-compartmental pressure in the anterior and deep posterior compartments of 52 patients with closed tibial fractures was measured at presentation and 4 hourly for 24 h. In three patients, the pressure was very high, and the differential pressure (i.e. the difference between the diastolic blood pressure and the intra-compartmental pressure) was less than or equal to [corrected] 30 mmHg, which was diagnostic of acute compartment syndrome. They were all treated by fasciotomy. It is concluded that Whitesides' [corrected] method can be used to diagnose acute compartment syndrome. The apparatus is easy to set up, cheap [corrected] and therefore ideal for use in our environment where sophisticated devices of tissue pressure measurement are not available.

Adolescent↗
PubMed2005

Increased computational accuracy in multi-compartmental cable models by a novel approach for precise point process localization.

Compartmental models of dendrites are the most widely used tool for investigating their electrical behaviour. Traditional models assign a single potential to a compartment. This potential is associated with the membrane potential at the centre of the segment represented by the compartment. All input to that segment, independent of its location on the segment, is assumed to act at the centre of the segment with the potential of the compartment. By contrast, the compartmental model introduced in this article assigns a potential to each end of a segment, and takes into account the location of input to a segment on the model solution by partitioning the effect of this input between the axial currents at the proximal and distal boundaries of segments. For a given neuron, the new and traditional approaches to compartmental modelling use the same number of locations at which the membrane potential is to be determined, and lead to ordinary differential equations that are structurally identical. However, the solution achieved by the new approach gives an order of magnitude better accuracy and precision than that achieved by the latter in the presence of point process input.

Computer Simulation↗
PubMed2005

Compartmentation of lactate originating from glycogen and glucose in cultured astrocytes.

Brain glycogen metabolism was investigated by employing isofagomine, an inhibitor of glycogen phosphorylase. Cultured cerebellar and neocortical astrocytes were incubated in medium containing [U-(13C)]glucose in the absence or presence of isofagomine and the amounts and percent labeling of intra- and extracellular metabolites were determined by mass spectrometry (MS). The percent labeling in glycogen was markedly decreased in the presence of isofagomine. Surprisingly, the percent labeling of intracellular lactate was also decreased demonstrating the importance of glycogen turnover. The decrease was limited to the percent labeling in the intracellular pool of lactate, which was considerably lower compared to that observed in the medium in which it was close to 100%. These findings indicate compartmentation of lactate derived from glycogenolysis and that derived from glycolysis. Inhibiting glycogen degradation had no effect on the percent labeling in citrate. However, the percent labeling of extracellular glutamine was slightly decreased in neocortical astrocytes exposed to isofagomine, indicating an importance of glycogen turnover in the synthesis of releasable glutamine. In conclusion, the results demonstrate that glycogen in cultured astrocytes is continuously synthesized and degraded. Moreover, it was found that lactate originating from glycogen is compartmentalized from that derived from glucose, which lends further support to a compartmentalized metabolism in astrocytes.

Amino Acids↗
PubMed1977

A computer program for the analysis of controllability, observability and structural identifiability of biological compartmental systems.

A computer program to check structural identifiability of biological compartmental systems, that is the priori possibility of estamating all unknown system parameters through a multi input-multi output tracer experiment is presented. The procedure, as based only on the adopted compartmental structure and the chosen input-output experiment, is independent of the numerical values of the parameters: therefore the program can be usefully employed before parameter estimation algorithms, to assure that all the unknown parameters evidenced in the model can be estimated from the experimental data. After a short review on compartmental models, controllability observability and structural identifiability are defined and techniques to check them are provided. The digital computer implementation of the whole procedure is discussed in detail. Some typical program runs regarding the application to biological systems are given.

Computers↗
PubMed1990

Horizontal compartmentation in the germinal matrices and intermediate zone of the embryonic rat cerebral cortex.

Cellular compartmentation was studied in the germinal matrices and the intermediate zone of the cerebral cortex of rat embryos that survived for 1 or more days after injection with [3H]thymidine. In contrast to the vertical compartmentation seen in the neuroepithelium with short-survival thymidine autoradiography, sequential-survival autoradiography revealed a horizontal compartmentation both in the germinal matrices and the intermediate zone. In the neuroepithelium of embryos that survived for 24 h, the differentially labeled cells form two distinct horizontal bands. The band overlapping with the mitotic zone is composed of heavily labeled cells, whereas the band overlapping with the synthetic zone is composed of lightly labeled cells. This indicates that there are two proliferative cell populations within the neuroepithelium, one turning over fast and the other more slowly. In the cortical intermediate zone of the same embryos several horizontal bands are present. Of these, the dispositions of two bands of heavily labeled cells--the superior band and the inferior band--were followed for several days. The superior band is apparently composed of glial cells that disperse in the direction of the internal capsule and the corpus callosum. In contrast, the inferior band (which overlaps with the subventricular zone where many cells are horizontally oriented) is apparently composed of sojourning young neurons. The cells of the inferior band resume their migration toward the cortical plate after a pause of 1-2 days. These observations call for a reappraisal of the view that young cortical neurons follow a direct radial path to the cortical plate.

Animals↗
PubMed1989

Hidden oscillations in generalized linear mammaillary compartmental models.

Oscillations due to complex eigenvalues, known to exist but difficult to detect, are sometimes totally hidden in the output of compartmental models, i.e., none of their modes appear in the output. An example is constructed of a class of linear compartmental models with complex eigenvalues, which have oscillating modes appearing in the output for some single-pool-input/single-pool-output (SpISpO) configurations, while for other such configurations all oscillations are totally hidden in the output. To generate the example, generalized mammillary compartmental models are defined in which a central pool exchanges with peripheral submodels called clusters, through individual connector pools, and their transfer functions are calculated corresponding to all SpISpO configurations. When such a model is repetitive, i.e., when it has identical peripheral clusters, and the input or the output is in the central pool, then it is zero-state equivalent, up to a multiplicative constant, with a reduced model having one peripheral cluster only. We analyze the visibility of an eigenvalue, i.e., whether or not the modes associated with it appear in the output, for repetitive generalized mammillary models. Sufficient conditions are given for such models to have oscillating modes appearing in the impulse response for some input/output configurations, while for other such configurations all oscillations are totally hidden, i.e., none appear in the output. A particularly interesting example is presented of a class of linear models with complex eigenvalues satisfying these conditions. This class has the structure of nonlinear models used to describe the process of protein synthesis and turnover.

Animals↗
PubMed1991

Indistinguishability and identifiability analysis of linear compartmental models.

Two compartmental model structures are said to be indistinguishable if they have the same input-output properties. In cases in which available a priori information is not sufficient to specify a unique compartmental model structure, indistinguishable model structures may have to be generated and their attributes examined for relevance. An algorithm is developed that, for a given compartmental model, investigates the complete set of models with the same number of compartments and the same input-output structure as the original model, applies geometrical rules necessary for indistinguishable models, and test models meeting the geometrical criteria for equality of transfer functions. Identifiability is also checked in the algorithm. The software consists of three programs. Program 1 determines the number of locally identifiable parameters. Program 2 applies several geometrical rules that eliminate many (generally most) of the candidate models. Program 3 checks the equality between system transfer functions of the original model and models being tested. Ranks of Jacobian matrices and submatrices and other criteria are used to check patterns of moment invariants and local identifiability. Structural controllability and structural observability are checked throughout the programs. The approach was successfully used to corroborate results from examples investigated by others.

Computer Simulation↗
PubMed1985

A technique for the long term measurement of intra-compartmental pressure in the lower leg.

The early diagnosis of an acute compartmental pressure syndrome is often difficult, but can be facilitated by long term, up to several days, measurement of intra-compartmental pressures. A measuring system has been developed, together with its associated surgical and operational procedures, which may be applied in a variety of situations, including an immobile patient or a patient mobilized following surgery. If the technique is adopted as soon as the patient enters hospital, or immediately postoperatively, an acute compartmental syndrome may be recognized early and measures taken to alleviate its consequences.

Biomedical Engineering↗
PubMed1994

A framework for building and simulating qualitative models of compartmental systems.

This paper describes a framework, called QCMF (Qualitative Compartmental Modeling Framework), which assists the user in formulating models of a pathophysiological system and in analyzing their behaviors through the simulation of the effects of a variety of pathogenetic mechanisms and therapeutical treatments. QCMF has adopted the compartmental theory as modeling ontology: a system is represented as a finite set of interacting compartments. The user enters, through an iconic language and menus, the compartmental structure of a pathophysiological system and the definition of the kinds of functional relationships describing the interactions between compartments. Then, QCMF automatically generates a behavior model of the system. Such a model consists of a set of ordinary differential equations, which are qualitatively expressed, and is directly coded into the language which is interpreted by the simulation algorithm. The system behavior can be obtained by simulating the model starting from an initial state which describes the perturbations acting on the system. The code defining the initial state is automatically built by QCMF as well. Finally, explanations of the predicted behavior are also automatically generated.

Algorithms↗
PubMed1988

Evidence against major compartmentalization of H+ in ischemic rat brain tissue.

Ischemia leads to intracellular acidosis, the severity of which depends on the availability of glucose for production of lactate and H+. It has been suggested that major compartmentalization of H+ occurs, with glial cells becoming much more acidotic than neurons. Since this issue is of crucial importance for the understanding of mechanisms of ischemic brain damage, we induced complete ischemia by decapitation in hypo-, normo- and hyperglycemic awake rats, yielding brain tissue lactate contents varying between 4 and 27 mumol/g. Using phosphorus nuclear magnetic resonance (NMR) we explored whether a splitting of the phosphorus peak occurred as a reflection of compartmentalization. Forebrains were put in NMR tubes and spectra obtained 15 min after decapitation. Since no such splitting was observed, we conclude that major compartmentalization does not occur in ischemia at the degrees of lactic acidosis studied.

Animals↗
PubMed1989

Compartmental origins of striatal efferent projections in the cat.

Injections of the retrograde tracer, wheat germ agglutinated-horseradish peroxidase were placed in the substantia nigra, in adjoining dopamine-containing cell groups A8 and A10, and in the internal and external parts of the pallidal complex of 20 cats in order to identify the compartmental origins of striatal efferent projections to the pallidum and midbrain. Patterns of retrograde cell-labeling in the caudate nucleus were analysed with respect to its striosomal architecture as detected in sections stained for acetylcholinesterase. Where possible, a similar compartmental analysis of cell-labeling in the putamen was also carried out. In 15 cats anterograde labeling in the striatum was studied in the sections stained with wheat germ agglutinated-horseradish peroxidase or in autoradiographically treated sections from cases in which [35S]methionine was mixed with the wheat germ agglutinated-horseradish peroxidase in the injection solution. Predominant labeling of projection neurons lying in striosomes (usually with some labeling of dorsomedial matrix neurons) occurred in a subset of the cases of nigral injection, including all cases (n = 9) in which the injection sites were centered in the densocellular zone of the substantia nigra pars compacta [Jiménez-Castellanos J. and Graybiel A. M. (1987) Neuroscience 23, 223-242.] Dense labeling of neurons in the extrastriosomal matrix, with at most sparse labeling of striosomal neurons, occurred in all cases of pallidal injection (n = 8) and in two cases of nigral injection in which the injection sites were lateral and anterior to the densocellular zone. Mixed labeling of striosomal and matrical neurons occurred in a third group of cases in which the injection sites were lateral to the densocellular zone but close to it. In a single case with an injection site situated in the pars lateralis of the substantia nigra, there was preferential labeling of striosomal neurons in the caudal caudate nucleus but widespread labeling of neurons in both striosomes and matrix in the putamen. A second type of compartmental ordering of projection neurons was found in the extrastriosomal matrix of the striatum. In cases of pallidal and nigral injection, there were gaps in cell labeling that did not match striosomes precisely, and often clusters of labeled cells appeared that did not correspond to acetylcholinesterase-poor striosomes but, instead, to patches of matrix. Especially prominent were clusters beside striosomes. There was a topographic ordering of striatal projection neurons both in the striosomes and in the extrastriosomal matrix according to their dorsoventral and latitudinal positions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Heterogeneous and compartmental distribution of zinc in the striatum and globus pallidus of the rat.

The distribution of vesicular or chelatable zinc was analysed in the dorsal and ventral subdivisions of the striatum and globus pallidus of the rat with Danscher's selenium method. Acetylcholinesterase and Calbindin-D28k were used as striatal and pallidal markers in order to analyse the possible compartmentalization of the distribution of zinc in the striatum and globus pallidus. The main findings of this study are the following: (1) The distribution of vesicular zinc in the dorsal striatum was heterogeneous. A peripheral rim of tissue heavily stained for zinc was detected in the medial, dorsal and lateral striatal areas, along most of the rostrocaudal extent of the striatum. addition, patch-like zones intensely stained for zinc were prominent in the rostral half of the caudate-putamen complex. (2) In some regions of the rostral half of the caudate-putamen complex, the staining for zinc appeared to follow the well-known striatal patches (striosomes)/matrix organization. However, in other regions of the rostral half of the striatum such a relation was not detected. (3) The ventral striatum also showed a heterogeneous staining for zinc. Thus, in the most ventral part of the caudate-putamen complex, both subdivisions of the nucleus accumbens and parts of the olfactory tubercle displayed different patterns of compartmentalized distribution of zinc. In the dorsal half of the shell of the nucleus accumbens, some patches with an intense reaction for zinc seemed to overlap with acetylcholinesterase-poor patches. (4) There was a remarkable absence of staining for zinc in the globus pallidus. This histochemical study illustrates, on the one hand, the high content of vesicular zinc in the dorsal and ventral subdivisions of the striatum, which was distributed following different patterns of chemical compartmentalization, and on the other hand, the absence of vesicular zinc in the globus pallidus of the rat.

Acetylcholinesterase↗
PubMed2006

Ultra-radical compartmentalized surgery in gynaecological oncology.

AIMS: To describe "ultra-radical" surgery in gynaecological oncology. This is multivisceral pelvic resection aimed at the eradication of locally advanced and recurrent gynaecologic cancer with microscopically tumour-free margins (R0). METHODS: Up-dated analysis of a prospective trial evaluating oncologic outcome and treatment-related morbidity of ultra-radical compartmentalized surgery carried out by the author. RESULTS: From 8/1996 until 9/2005 74 patients with locally advanced and recurrent gynaecologic tumours have been treated with ultra-radical compartmentalized surgery. Eighteen patients with central disease underwent exenteration as multimesovisceral excision, 56 patients with pelvic side wall disease received laterally extended endopelvic resection. In 72 of the patients the tumours were removed with microscopically free margins (R0). Two patients with advanced age and extensive comorbidity respectively, died during the early postoperative period. Moderate and severe treatment-related morbidity was 66%. At a median follow-up period of 29 months (1-112 months) 5-year overall and recurrence-free survival probabilities are 56% (95% CI: 42-69) and 56% (42-70). CONCLUSION: Ultra-radical compartmentalized pelvic surgery may salvage selected patients with locally advanced and recurrent gynaecologic malignancies including those with pelvic side wall disease traditionally not considered for surgical therapy.

Adult↗
PubMed2006

A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia.

There is much uncertainty about cancer risks at the high radiation doses used in radiotherapy (RT). It has generally been assumed that cancer induction decreases rapidly at high doses due to cell killing. However, this is not seen in all RT groups, and a model recently developed by Sachs and Brenner [2005. Solid tumor risks after high doses of ionizing radiation. Proc. Natl Acad. Sci. USA 102, 13040-13045] proposed a mechanism for repopulation of cells after radiation exposure that explained why this might happen, at least for solid tumours. In this paper, this model is generalized to allow for heterogeneity in the dose received, and various alternate patterns of repopulation are also considered. The model is fitted to the Japanese atomic bomb survivor leukaemia incidence data, and data for various therapeutically irradiated groups. Two sets of parameters from these model fits are used to assess the sensitivity of model predictions. It is shown that in general allowing for heterogeneity in dose distribution and haematopoietic stem cell migration results in lower risks than the same average dose administered uniformly and without such migration, although this does not hold in the limiting case of complete stem cell repopulation between radiation dose fractions. We also investigate the difference made by assuming a compartmental repopulation signal, and a global repopulation signal. In general we show that in the absence of stochastic extinction, compartmental repopulation always predicts a larger number of mutated cells than global repopulation. However, in certain dose regimes stochastic extinction cannot be ignored, and in these cases the numbers of mutated cells predicted with global repopulation can exceed that for compartmental repopulation. In general, mutant cell numbers are highly overdispersed, with variance much greater than the mean.

Cell Count↗
PubMed2005

GRP78 compartmentalized redistribution in Pb-treated glia: role of GRP78 in lead-induced oxidative stress.

Glucose-regulated protein of 78 kDa (GRP78) is an endoplasmic reticulum (ER) molecular chaperone functioning in protein folding, assembly and trafficking. GRP78 also plays a role in protection against cytotoxicity and apoptosis induced by environmental insults. Our previous study showed that lead (Pb) directly targets GRP78 by binding to the protein and increasing GRP78 levels. In this study, the effect of Pb on compartmentalized distribution of GRP78 in living cells was examined. A rat GRP78-EGFP fusion protein and EGFP were transiently expressed in astrocytoma cells exposed to 5 microM Pb acetate or 50 microM CuSO4 and fluorescence signals were captured. Control cells expressing EGFP showed a homogeneous distribution of EGFP that was not changed by Pb or Cu treatment. Cells expressing GRP78-EGFP showed a compartmentalized, non-homogeneous distribution of GRP78-EGFP in the cytosol. The redistribution of GRP78-EGFP fluorescent bodies was observed in cells exposed to Pb for 10 h, but not 5 h. Redistribution was also observed in cells exposed to 50 microM Cu for 5 or 10 h. To assess GRP78 function, GRP78 was depleted with dsRNAi oligos in rat C6 glioma cells. GRP78 depletion significantly increased the sensitivity of cells to Pb exposure as indicated by the generation of reactive oxygen species (ROS). These data suggest that Pb directly targets GRP78 and induces its compartmentalized redistribution in living cells and that GRP78 plays a protective role in Pb neurotoxicity.

Animals↗
PubMed2006

Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated channel 2 and hyperpolarization-activated cyclic-nucleotide-gated channel 4 in thalamic reticular and thalamocortical relay neurons.

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels conduct a monovalent cationic current, I(h), which contributes to the electrophysiological properties of neurons and regulates thalamic oscillations in circuits containing the glutamatergic ventrobasal complex (VB) and GABAergic reticular thalamic nucleus (RTN). Four distinct HCN channel isoforms (HCN1-4) have been identified, and mRNAs and proteins for HCN channels have been detected in the RTN and VB, with HCN2 and HCN4 being the predominant isoforms. RTN and VB neurons have distinct electrophysiological properties, and those differences may reflect variable compartmental distribution of HCN channels. Whole cell patch clamp recordings from thalamic neurons in brain slices obtained from C57/Bl6 mice demonstrate that I(h) is much smaller in RTN than in VB neurons although the time constants for I(h) current activation are very similar. To study the compartmental distribution of the underlying channels, we performed qualitative and quantitative examination of HCN2 and HCN4 expression using fluorescent immunohistochemistry and confocal microscopy. HCN2-immunoreactivity (IR) on the somata of RTN neurons was approximately 10-fold less than that seen in VB neurons while HCN4-IR was detected on the somata of RTN and VB neurons to an equal degree. HCN2-IR in RTN and VB did not overlap with synaptophysin-IR, but strongly colocalized with cortactin-IR, indicating that HCN2 was not present in axon terminals but was present in dendritic spines. Although HCN2-IR in spines was more pronounced in VB than in RTN, the ratio of spinous to somatic expression in RTN was dramatically higher than that in VB, strongly suggesting that HCN2-IR in RTN is principally located in sites distal to the soma. In contrast, HCN4-IR did not colocalize with either synaptophysin or cortactin. The colocalization of HCN2-IR with HCN4-IR was greater in VB than in RTN. The results suggest that the distinct compartmental distribution of HCN2 channels in RTN and VB neurons contributes to the profound differences in the I(h)-dependent properties of these cells.

Animals↗
PubMed1998

Steady-state compartmentalization of lipid membranes by active proteins.

Using a simple microscopic model of lipid-protein interactions, based on the hydrophobic matching principle, we study some generic aspects of lipid-membrane compartmentalization controlled by a dispersion of active integral membrane proteins. The activity of the proteins is simulated by conformational excitations governed by an external drive, and the deexcitation is controlled by interaction of the protein with its lipid surroundings. In response to the flux of energy into the proteins from the environment and the subsequent dissipation of energy into the lipid bilayer, the lipid-protein assembly reorganizes into a steady-state structure with a typical length scale determined by the strength of the external drive. In the specific case of a mixed dimyristoylphosphatidylcholine-distearoylphosphatidylcholine bilayer in the gel-fluid coexistence region, it is shown explicitly by computer simulation that the activity of an integral membrane protein can lead to a compartmentalization of the lipid-bilayer membrane. The compartmentalization is related to the dynamical process of phase separation and lipid domain formation.

Computer Simulation↗
PubMedDate not supplied

Density functions of residence times for deterministic and stochastic compartmental systems.

A significant consideration in modeling systems with stages is to obtain models for the individual stages that have probability density functions (pdfs) of residence times that are close to those of the real system. Consequently, the theory of residence time distributions is important for modeling. Here I show first that linear deterministic compartmental systems with constant coefficients and their corresponding stochastic analogs (stochastic compartmental systems with linear rate laws) have the same pdfs of residence times for the same initial distributions of inputs. Furthermore, these are independent of inflows. Then I show that does not hold for non-linear deterministic systems and their stochastic analogs (stochastic compartmental systems with non-linear rate laws). In fact, for given initial distributions of inputs, the pdfs of non-linear determistic systems without inflows and of their stochastic analogs, are functions of the initial amounts injected. For systems with inflows, the pdfs change as the inflows influence the occupancies of the compartments of the system; they are state-dependent pdfs.

Kinetics↗