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PubMed1995

Structural identifiability and indistinguishability of certain two-compartment models incorporating nonlinear efflux from the peripheral compartment.

A two-compartment model is considered where both compartments are observed and where the transfer efflux from the peripheral compartment may take three different nonlinear forms. The structural identifiability of the set of unknown parameters of each possible model is examined using the similarity transformation approach. Using the recent extension of this approach the indistinguishability of pairs of the postulated systems is also considered.

Animals↗
PubMedDate not supplied

Computer-assisted image analysis techniques allow a characterization of the compartments within the basal ganglia. Focus on functional compartments produced by d-amphetamine activation of the c-fos gene and its relationship to the glucocorticoid receptor.

A new computer-assisted image analysis procedure was developed for the analysis of striatal compartments of the rats visualized in this case by means of c-fos immunocytochemistry after morphine and/or d-amphetamine treatments. In particular it has been shown that d-amphetamine can induce an activation of the c-fos early gene in various subregions of the neostriatum and that morphine treatment can antagonize this activation. A different pattern of morphine antagonistic action could be detected at the rostral versus the caudal striatal level. In fact, at the rostral level the morphine antagonistic action was very marked only in the dorsomedial striatum, while at the caudal level the morphine antagonistic action was marked in all subregions. The developed computer-assisted procedure can detect differences in the pattern of distribution of profiles present in a certain neuroanatomical area. Therefore, this procedure may represent a powerful tool to study integrative functional compartments in the neostriatum. In the present study high level integrative compartments appear to be created by D1/mu-opiate receptor interactions especially within the classical patch system.

Animals↗
PubMed1999

Apolipoprotein B stimulates formation of monocyte-macrophage surface-connected compartments and mediates uptake of low density lipoprotein-derived liposomes into these compartments.

Much of the cholesterol that accumulates in atherosclerotic plaques is found within monocyte-macrophages transforming these cells into "foam cells." Native low density lipoprotein (LDL) does not cause foam cell formation. Treatment of LDL with cholesterol esterase converts LDL into cholesterol-rich liposomes having >90% cholesterol in unesterified form. Similar cholesterol-rich liposomes are found in early developing atherosclerotic plaques surrounding foam cells. We now show that cholesterol-rich liposomes produced from cholesterol esterase-treated LDL can cause human monocyte-macrophage foam cell formation inducing a 3-5-fold increase in macrophage cholesterol content of which >60% is esterified. Although cytochalasin D inhibited LDL liposome-induced macrophage cholesteryl ester accumulation, LDL liposomes did not enter macrophages by phagocytosis. Rather, the LDL liposomes induced and entered surface-connected compartments within the macrophages, a unique endocytic pathway in these cells that we call patocytosis. LDL liposome apoB rather than LDL liposome lipid mediated LDL liposome uptake by macrophages. This was shown by the findings that: 1) protease treatment of the LDL liposomes prevented macrophage cholesterol accumulation; 2) liposomes prepared from LDL lipid extracts did not cause macrophage cholesterol accumulation; and 3) purified apoB induced and accumulated within macrophage surface-connected compartments. Although apoB mediated the macrophage uptake of LDL liposomes, this uptake did not occur through LDL, LDL receptor-related protein, or scavenger receptors. Also, LDL liposome uptake was not sensitive to treatment of macrophages with trypsin or heparinase. Cholesterol esterase-mediated transformation of LDL into cholesterol-rich liposomes is an LDL modification that: 1) stimulates uptake of LDL cholesterol by apoB-dependent endocytosis into surface-connected compartments, and 2) causes human monocyte-macrophage foam cell formation.

Apolipoproteins B↗
PubMed1998

Safety and efficacy of a two-compartment Bayesian feedback program for therapeutic tobramycin monitoring in the daily clinical use and comparison with a non-Bayesian one-compartment model.

The predictive value of a two-compartment Bayesian feedback program for tobramycin dose optimization was retrospectively evaluated in 199 hospitalized patients and compared with that of a simple non-Bayesian one-compartment model. Before dose adjustment, 64% of the patients were underdosed indicating that tobramycin monitoring is still necessary to avoid ineffective antibiotic therapy. When physicians adhered to the dose instructions calculated with the Bayesian method, 90% of the patients had optimal concentration-time profiles as opposed to only 53% of the 43 patients in whom dose recommendations were not followed. In young patients with normal renal function, precision and accuracy of the Bayesian feedback and the one-compartment method were well correlated, whereas in elderly patients (> 60 years) and patients with impaired renal function (estimated creatinine clearance < 60 ml/minute), the Bayesian method was significantly more precise. Multiple regression analysis revealed that renal function was the only independent variable predicting the performance of the Bayesian program. The results of this study indicate that the Bayesian feedback method is a reliable method for the therapeutic tobramycin monitoring under clinical conditions and in particular, elderly patients in whom renal impairment is frequent.

Absorption↗
PubMed2006

Spermidine synthase is prominently expressed in the striatal patch compartment and in putative interneurones of the matrix compartment.

The ubiquitous polyamines spermidine and spermine are known as modulators of glutamate receptors and inwardly rectifying potassium channels. They are synthesized by a set of specific enzymes in which spermidine synthase is the rate-limiting step catalysing the formation of the spermine precursor spermidine from putrescine. Spermidine and spermine were previously localized to astrocytes, probably reflecting storage rather than synthesis in these cells. In order to identify the cellular origin of spermidine and spermine synthesis in the brain, antibodies were raised against recombinant mouse spermidine synthase. As expected, strong spermidine synthase-like immunoreactivity was obtained in regions known to express high levels of spermidine and spermine, such as the hypothalamic paraventricular and supraoptic nuclei. In the striatum, spermidine synthase was found in neurones and the neuropil of the patch compartment (striosome) as defined by expression of the micro opiate receptor. The distinct expression pattern of spermidine synthase, however, only partially overlapped with the distribution of the products spermidine and spermine in the striatum. In addition, spermidine synthase-like immunoreactivity was seen in patch compartment-apposed putative interneurones. These spermidine synthase-positive neurones did not express any marker characteristic of the major striatal interneurone classes. The neuropil labelling in the patch compartment and in adjacent putative interneurones may indicate a role for polyamines in intercompartmental signalling in the striatum.

Animals↗
PubMedDate not supplied

A compartment model to calculate time-dependent concentration profiles of topically applied chemical compounds in the anterior compartments of the rabbit eye.

Hitherto, none of the existing in vitro methods has been convincingly demonstrated to be suitable as a replacement for the Draize rabbit eye irritation test. We examine the hypothesis that one reason for this is that insufficient consideration has been given to the differences in the effective concentrations at which chemicals operate in vitro and in vivo. When a chemical is applied topically to the eye, the strength of the observed irritation that it elicits depends both on its toxic potential toward cells or tissues, and its effective concentration in the tissues of the eye. Most of the existing in vitro methods are based on isolated cells or tissues, and thus may be useful in assessing the cytotoxic potentials of chemicals. However, a reliable approach to assessing the effective concentrations of chemicals within the various tissues of the eye is lacking. A simplified compartment model is presented for calculating the time-dependent, intra-ocular concentration profiles of topically applied chemicals. The model encompasses the outer surface of the eye, three distinct segments of the cornea (subdivided into the epithelium, stroma and endothelium) and the conjunctiva. Transport through the membranes of these compartments is described as passive diffusion. For the transport coefficients, rate equations are established that contain, as free parameters, the molecular size and the partition coefficient of the chemical, as well as some intrinsic membrane parameters, such as thickness, viscosity and pore density. Numerical values for the unknown membrane parameters were estimated by fitting the theoretical rate equations to measured permeability coefficients. The compartment model was applied to an independent set of 52 test chemicals compiled from the European Commission/UK Home Office validation study. The calculated passage times (required to let 95% of the chemical reach the posterior eye tissues) varied between 0.33 minutes and 50.6 minutes, and are generally much shorter than the typical duration of observed impairments in the cornea or conjunctiva. This finding suggests that short-term contacts of the eye tissues with a chemical are sufficient to elicit long-term eye irritation. An example is given, showing how the conventional approach of using in vitro endpoints as predictors of eye irritation can be improved significantly by incorporating into the prediction the calculated intra-ocular concentration of a chemical.

4-Butyrolactone↗
PubMed2003

Comparing the methods of measuring compartment pressures in acute compartment syndrome.

The objectives of this study were to compare the reliability and accuracy of published methods of measuring intramuscular compartment pressures. A muscle compartment model was constructed. Pressure was standardized using a water column exerting pressure on a muscle slab. The following three methods of intracompartmental pressure were used to measure the pressure within the muscle slab of the model: (1) Stryker, (2) manometric IV pump, and (3) Whitesides method. The Stryker and IV pump methods were similarly accurate compared with the "standard pressure." The Whitesides method was not reliable in measuring a reproducible pressure. The IV pump method is comparable to the Stryker instrument in terms of accuracy and ease of use. If a Stryker instrument is unavailable, the IV pump method can serve as a suitable and satisfactory alternative.

Acute Disease↗
PubMed1980

Accumulation in the peripheral compartment of a linear two-compartment open model.

Accumulation factors for the peripheral compartment in a two-compartment open model are derived. These expressions are contrasted with some previously published statements concerning drug accumulation. The utility of the new indices of accumulation is illustrated by reference to studies of gentamicin tissue.uptake and its proposed relation to nephrotoxicity.

Gentamicins↗
PubMed2001

Body fat measurement among Singaporean Chinese, Malays and Indians: a comparative study using a four-compartment model and different two-compartment models.

This cross-sectional study compared body fat percentage (BF%) obtained from a four-compartment (4C) model with BF% from hydrometry (using 2H2O), dual-energy X-ray absorptiometry (DXA) and densitometry among the three main ethnic groups (Chinese, Malays and Indians) in Singapore, and determined the suitability of two-compartment (2C) models as surrogate methods for assessing BF% among different ethnic groups. A total of 291 subjects (108 Chinese, seventy-six Malays, 107 Indians) were selected to ensure an adequate representation of age range (18-75 years) and BMI range (16-40 kg/m2) of the general adult population, with almost equal numbers from each gender group. Body weight was measured, together with body height, total body water by 2H2O dilution, densitometry with Bodpod and bone mineral content with Hologic QDR-4500. BF% measurements with a 4C model for the subgroups were: Chinese females 33.5 (sd 7.5), Chinese males 24.4 (sd 6.1), Malay females 37.8 (sd 6.3), Malay males 26.0 (sd 7.6), Indian females 38.2 (sd 7.0), Indian males 28.1 (sd 5.5). Differences between BF% measured by the 4C and 2C models (hydrometry, DXA and densitometry) were found, with underestimation of BF% in all the ethnic-gender groups by DXA of 2.1-4.2 BF% and by densitometry of 0.5-3.2 BF%). On a group level, the differences in BF% between the 4C model and 2H2O were the lowest (0.0-1.4 BF% in the different groups), while differences between the 4C model and DXA were the highest. Differences between the 4C model and 2H2O and between the 4C model and DXA were positively correlated with the 4C model, water fraction (f(water)) of fat-free mass (FFM) and the mineral fraction (f(mineral)) of FFM, and negatively correlated with density of the FFM (D(FFM)), while the difference between 4C model and densitometry correlated with these variables negatively and positively respectively (i.e. the correlations were opposite). The largest contributors to the observed differences were f(water) and D(FFM). When validated against the reference 4C model, 2C models were found to be unsuitable for accurate measurements of BF% at the individual level, owing to the high errors and violation of assumptions of constant hydration of FFM and D(FFM) among the ethnic groups. On a group level, the best 2C model for measuring BF% among Singaporeans was found to be 2H2O.

Absorptiometry, Photon↗
PubMed2003

Bayesian two-compartment and classic single-compartment minimal models: comparison on insulin modified IVGTT and effect of experiment reduction.

Models describing plasma glucose and insulin concentration of an intravenous glucose tolerance test (IVGTT) allow a noninvasive cost-effective approach to estimate important indexes characterizing the efficiency of glucose-insulin control system, i.e., glucose effectiveness (S(G)) and insulin sensitivity (S(I)). To overcome some limitations of the classic single compartment minimal model (1CMM) of glucose kinetics , a two-compartment Bayesian minimal model (2CBMM) has been recently proposed for the standard IVGTT. This study aims to assess 2CBMM ability to describe the insulin-modified IVGTT (IM-IVGTT) which is the protocol of choice since it allows to study insulinopenic states. Both a full-length IM-IVGTT (240 min) as well as a reduced version (90 min) of it are studied. Results of the maximum a posteriori identification of IM-IVGTT (240 min) in 13 normals agree with those of standard IVGTT, i.e., a 42% decrease (P < 0.002) of S(G) and a 13% increase (P < 0.006) of S(I) with respect to ICMM. When identified from IM-IVGTT (90 min), 2CBMM not only provides S(G) and S(I) estimates 46% lower (P < 0.002) and 41% higher (P < 0.002) than 1CMM ones respectively, but also seems to overcome some limitations of the 240 min-based identification that probably arise because the minimal model is unable to properly account for the hyperglycemic hormonal response taking place in the second half of IM-IVGTT.

Bayes Theorem↗
PubMed1999

Increased extracellular water compartment, relative to intracellular water compartment, after weight reduction.

The hydration of fat free mass (FFM) and extracellular (ECW) and intracellular water (ICW) compartments were studied in 30 obese premenopausal women before and after a 3-mo weight-reduction program and again after a 9-mo weight-maintenance program. Body fat was determined by a four-compartment model. Total body water and ECW were determined by deuterium dilution and bromide dilution, respectively. After the weight-reduction period, mean weight loss was 12.8 kg, and body fat was reduced on average by 10.9 kg. During weight maintenance, changes in body mass and body fat were not significant. Before weight reduction, mean ECW/ICW ratio was relatively high (0.78 +/- 0.10). During the the study, total body water and ICW did not change significantly. ECW did not change significantly after weight reduction, but 12 mo after the start ECW was significantly increased by 1 liter. The ECW/ICW ratio increased to 0.87 +/- 0.12 (month 12). The hydration of the FFM increased from 74 +/- 1 to 77 +/- 2% during the weight reduction and remained elevated during weight maintenance. In conclusion, the ECW/ICW ratio and the hydration of the FFM, did not normalize during weight reduction and weight maintenance.

Adipose Tissue↗
PubMed1997

[Compartment syndrome. Exclusively the result of increased pressure in the muscular compartment?].

The compartment syndrome (cs) is characterized by an increased tissue pressure in a limited space. Pathophysiologically, it is a multifactorial disease that is potentially induced by an initial trauma and develops according to the existence of cofactors. Cofactors are, for instance, the circulation of the patient and the initial treatment of the impending cs. In particular, the microcirculation is altered with endothelial destruction, development of a capillary leak, protein loss from intravasal space and the development of an interstitial and intracellular third space. An impaired drainage of the lymphatic and venous system causes a venous infarction. An arterial infarction results if the tissue pressure exceeds the arteriolar pressure. An accompanying ischemia reperfusion mechanism increases the trauma load. In disadvantageous cases, the patients are in danger of developing a multi-organ deficiency syndrome (MODS) by an uncontrolled inflammatory reaction, by intravasal volume loss and by a myonephropathic systemic reaction. Clinically, the patients suffer a disproportionate amount of pain, followed by neurological signs. Especially in noncompliant patients, tissue pressure measurement is useful. Resuscitation of the circulation as well as splitting of casts is important. In case of a manifest cs, dermatofasciotomy has to be performed as an emergency operation. Even if cs is diagnosed early and fasciotomy is carried out early, the development of sequellae cannot be avoided in every single case.

Compartment Syndromes↗
PubMedDate not supplied

[Fascia compartment syndrome of the iliac-psoas compartment].

The iliacus compression syndrome has a kind of exceptional position--as to genesis, development and therapy--in comparison with the other compartment-compression syndromes of the limbs. Indeed there exist similar pathophysiological, rules, but the special anatomic facts enlarge the etiological, differential-diagnostic and therapeutic spectrum. Thus, concerning the frequency of causes, not the trauma but the spontaneous bleeding in coagulation disturbances takes the first place, and unusual causes, such as rupturing aortic aneurysms, have to be included in the differential diagnostic discussion. The finest diagnostic sign besides pain is the palsy of the Nervus Femoralis. As to the treatment, operative measures are possible. The exact knowledge of the anatomy is important for the understanding of the specialties mentioned above.

Adult↗
PubMed1993

Chronic exertional compartment syndrome: correlation of compartment pressure and muscle ischemia utilizing 31P-NMR spectroscopy.

In the past 5 years, a great deal of time and effort has been expended in an effort to better define clinical, anatomic, and laboratory parameters of CECS. It is now a well-recognized entity and one that can be readily resolved with fasciotomy. But the reasons for predisposition and the pathophysiologic mechanisms remain obscure. It appears, however, that basing the decisions for fasciotomy on clinical characteristics alone leads to overdiagnosis and excessive surgery. In this series, almost 50% of the referred subjects failed to demonstrate adequate laboratory criterion for the diagnosis of CECS. Fasciotomy in these patients may have effected a cure, but the reasons may be unrelated to increased intracompartmental pressure. Furthermore, in the laboratory diagnosis of CECS, the rate of return to resting compartment pressure following exercise seems more accurate than reliance on resting pressure alone. 31P-NMR has proved valuable in the dynamic assessment of muscle ischemia as reflected by relative PCr concentrations. Finally, although a mechanism explaining the source of pain has not been established by this study, it appears that ischemia is not a significant factor.

Chronic Disease↗
PubMed1997

Internalized plasma membrane cholesterol passes through an endosome compartment that is distinct from the acid vesicle-lysosome compartment.

Cholesterol from the plasma membrane of MA-10 Leydig tumor cells is internalized into the cell and either esterified or used as substrate for steroid hormone synthesis. In the present studies we show that chloroquine and sphinganine cause LDL cholesterol and cholesteryl esters to accumulate in the cells. A lysosome fraction contained the excess cholesterol and cholesteryl esters. Both inhibitors blocked the conversion of plasma membrane cholesterol into intracellular cholesteryl esters and caused dose-dependent inhibition of dibutyryl-cAMP-stimulated progesterone synthesis. Radiolabeled cholesterol applied to the plasma membrane of MA-10 cells accumulated in the lysosome fraction of chloroquine and sphinganine-treated cells. Evidence that these inhibitors did not require the Golgi was provided by experiments using brefeldin A. Experiments utilizing a fluorescent cholesterol analogue and a lysosomal marker indicated that cholesterol entered the cells in structures that were different than the acidic vesicle-lysosome compartment. Consistent with this observation was the observation that the peak fluorescence fractions of cells subjected to density gradient centrifugation was of lower density than the lysosome fraction.

4-Chloro-7-nitrobenzofurazan↗
PubMed2000

Comparison of plasma compartment versus two methods for effect compartment--controlled target-controlled infusion for propofol.

BACKGROUND: Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI. METHODS: One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured. RESULTS: The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II. CONCLUSION: Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.

Adolescent↗
PubMed1984

[The anterior tibial artery and vascularization of the muscles of the anterior compartment of the leg. Application to the anterior compartment syndrome of the leg].

The arterial vascularisation of the anterior loge of the leg is supply by the anterior tibial artery. Three muscles are contained in an inextensible space. Each of this muscles received an arterial supply proportional to his volume. The fragility to ischemy of the extensor hallucis longus is not explained by insufficiency of this arterial branches.

Angiography↗