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PubMed2004

Compartmentalization of human immunodeficiency virus type 1 between blood monocytes and CD4+ T cells during infection.

Distinct sequences of human immunodeficiency virus type 1 (HIV-1) have been found between different tissue compartments or subcompartments within a given tissue. Whether such compartmentalization of HIV-1 occurs between different cell populations is still unknown. Here we address this issue by comparing HIV-1 sequences in the second constant region through the fifth hypervariable region (C2 to V5) of the surface envelope glycoprotein (Env) between viruses in purified blood CD14(+) monocytes and CD4(+) T cells obtained longitudinally from five infected patients over a time period ranging from 117 to 3,409 days postseroconversion. Viral populations in both cell types at early infection time points appeared relatively homogeneous. However, later in infections, all five patients showed heterogeneous populations in both CD14(+) monocytes and CD4(+) T cells. Three of the five patients had CD14(+) monocyte populations with significantly more genetic diversity than the CD4(+) T-cell population, while the other two patients had more genetic diversity in CD4(+) T cells. The cellular compartmentalization of HIV-1 between CD14(+) monocytes and CD4(+) T cells was not seen early during infections but was evident at the later time points for all five patients, indicating an association of viral compartmentalization with the time course of HIV-1 infection. The majority of HIV-1 V3 sequences indicated a macrophage-tropic phenotype, while a V3 sequence-predicted T-cell tropic virus was found in the CD4(+) T cells and CD14(+) monocytes of two patients. These findings suggest that HIV-1 in CD14(+) monocytes could disseminate and evolve independently from that in CD4(+) T cells over the course of HIV-1 infection, which may have implications on the development of new therapeutic strategies.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude and latency, and the effect of activating synapses individually or simultaneously. Process location affects peak latency and voltage recorded at the heminode. A synapse on a calyceal process produced < or = 8% more depolarization and a 23% increase in peak latency compared with a synapse on a process of a neuron branch. For whole primary afferents, depolarization decreased 40% between simulations of the smallest and largest afferents. Simulations in which membrane resistivity and synaptic conductance were varied while afferent geometry was kept constant indicated that use of 5,000 omega cm2 and 1.0 nS produced results that best fit electrophysiological findings. Synaptic inputs activated simultaneously did not sum linearly at the heminode. Total depolarization was approximately 14% less than a simple summation of responses of synapses activated one at a time.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Maculae↗
PubMed1984

Differential compartmentation of magnesium and calcium in murine S49 lymphoma cells.

28Mg2+ influx studies in S49 murine lymphoma cells indicate that only 2-3% of total cell Mg2+ content can be exchanged at isotopic equilibrium, implying compartmentation of the newly transported Mg2+. The nature of this compartmentation was examined using selective permeabilization of the plasma membrane with the detergent, digitonin. Control experiments demonstrated that the digitonin permeabilization procedure did not release mitochondrial and lysosomal components, alter mitochondrial respiration, or significantly change cell morphology. Thus, under appropriate conditions, the digitonin permeabilization technique allows determination of the amount of a particular cell constituent within the solute space of the cytoplasm. In nonproliferating cells at an extracellular Mg2+ concentration of 0.1 mM, newly transported Mg2+ equilibrates within 2 h with a small cytoplasmic Mg2+ pool comprising about 3% of the total cytoplasmic Mg2+ (about 2% of total cell Mg2+). The pool of Mg2+ does not equilibrate with bulk cytoplasmic or cellular Mg2+ for at least 16 h. The Mg2+ pool size is dependent on extra-cellular Mg2+ concentration, is saturable with increasing extracellular Mg2+, and reaches a maximal size of 6-7% of total cell Mg2+ at 2 mM extracellular Mg2+. Unlike Mg2+, newly transported Ca2+ is quickly sequestered in noncytoplasmic compartments. In proliferating cells, however, newly transported Mg2+ exchanges extensively with cytoplasmic Mg2+ over the course of 4 h, suggesting that compartmentation of Mg2+ may be dependent on proliferative status.

Animals↗
PubMed1998

Compartmental analysis of dopa decarboxylation in living brain from dynamic positron emission tomograms.

The trapping of decarboxylation products of radiolabelled dopa analogs in living human brain occurs as a function of the activity of dopa decarboxylase. This enzyme is now understood to regulate, with tyrosine hydroxylase, cerebral dopamine synthesis. Influx into brain of dopa decarboxylase substrates such as 6-[18F]fluorodopa and beta-[11C]dopa measured by positron emission tomography can be analyzed by solution of linear differential equations, assuming irreversible trapping of the decarboxylated products in brain. The isolation of specific physiological steps in the pathway for catecholamine synthesis requires compartmental modelling of the observed dynamic time-activity curves in plasma and in brain. The several approaches to the compartmental modelling of the kinetics of labelled substrates of dopa decarboxylase are now systematically and critically reviewed. Labelled catechols are extensively metabolized by hepatic catechol-O-methyltransferase yielding brain-penetrating metabolites. The assumption of a fixed blood-brain permeability ratio for O-methyl-6-[18F]fluorodopa or O-methyl-beta-[11C]dopa to the parent compounds eliminates several parameters from compartmental models. However, catechol-O-methyltransferase activity within brain remains a possible factor in underestimation of cerebral dopa decarboxylase activity. The O-methylation of labelled catechols is blocked with specific enzyme inhibitors, but dopa decarboxylase substrates derived from m-tyrosine may supplant the catechol tracers. The elimination from brain of decarboxylated tracer metabolites can be neglected without great prejudice to the estimation of dopa decarboxylase activity when tracer circulation is less than 60 minutes. However, elimination of dopamine metabolites from brain occurs at a rate close to that observed previously for metabolites of glucose labelled in the 6-position. This phenomenon can cause systematic underestimation of the rate of dopa decarboxylation in brain. The spillover of radioactivity due to the limited spatial resolution of tomographs also results in underestimation of dopa decarboxylase activity, but correction for partial volume effects is now possible. Estimates of dopa decarboxylase activity in human brain are increased several-fold by this correction. Abnormally low influx of dopa decarboxylase tracers in the basal ganglia is characteristic of Parkinson's disease and other movement disorders. Consistent with postmortem results, the impaired retention of labelled dopa is more pronounced in the putamen than in the caudate nucleus of patients with Parkinson's disease; this heterogeneity persists after correction for spillover. Current in vivo assays of dopa decarboxylase activity fail to discriminate clinically distinct stages in the progression of Parkinson's disease and are, by themselves, insufficient for differential diagnosis of Parkinson's disease and other subcortical movement disorders. However, potential new avenues for therapeutics can be tested by quantifying the rate of metabolism of exogenous dopa in living human brain.

Animals↗
PubMed1993

Antigenic compartmentation in the mouse cerebellar cortex: zebrin and HNK-1 reveal a complex, overlapping molecular topography.

Two monoclonal antibodies--anti-zebrin I and anti-HNK-1--have been used to study the compartmentation of the mouse cerebellar cortex. As in other species, the pattern of localization of the Purkinje cell specific antigen zebrin I is confined to a subset of Purkinje cells that are organized into parasagittal bands. The basic pattern consists of two abutting paramedian bands (P1+) and up to three additional vermal bands on either side (P2(+)-P4+). This pattern is altered in the vermal regions of lobules X and VI-VII where all Purkinje cells are immunoreactive. In the hemisphere there are three additional bands present (P5(+)-P7+) plus two shorter bands in the paravermal area (P4b+ and P5a+) that extend from the paramedian lobule through the lobulus simplex. This pattern is very similar, but perhaps not identical, to that previously described for the rat. These results suggest a common mammalian plan for the expression and localization of zebrin I. By using a monoclonal antibody to an epitope associated with HNK-1, we have now identified a novel pattern of compartmentation in mouse cerebellum. The HNK-1 epitope is expressed most notably on Purkinje cells and Golgi cells. The molecular layer immunoreactivity associated with the Purkinje cell dendrites varies in intensity in a systematic and reproducible fashion. This reveals a novel cerebellar compartmentation that is sometimes complementary, sometimes overlapping, to that revealed by anti-zebrin. As a result, it is now possible to subdivide the cerebellar cortex into a still finer mosaic of antigenic patches and bands than was possible by using zebrins alone.

Animals↗
PubMed1994

Functional and antigenic maps in the rat cerebellum: zebrin compartmentation and vibrissal receptive fields in lobule IXa.

The mammalian cerebellum is compartmentalized, both structurally and biochemically, into an array of parasagittal bands. In the adult rat, bands can be shown by immunocytochemical staining of a Purkinje cell subset with the monoclonal antibody antizebrin II. In contrast to the bands revealed by the zebrin II distribution, electrophysiological maps of tactile representations show an apparently quite different organization, a patchwork somatotopy of interwoven small receptive fields. We have compared zebrin II compartmentation with the distribution of vibrissal receptive fields in the dorsal face of lobule IXa. Nine adult rats were studied. Zebrin II immunocytochemistry revealed a zebrin II+ band at the midline (P1+) and three others (P2+, P3+, P4+) arrayed laterally, separated by the P1-, P2-, and P3- bands of unstained Purkinje cells. The only significant source of variability was that P3- was sometimes ill defined, making the P3+ and P4+ difficult to distinguish. Electrophysiological recording in the granular layer of lobule IXa identified two reproducible vibrissal receptive fields on each side of the midline (V1 and V2), with a third, more laterally, identified occasionally (V3). When receptive field maps were constructed and aligned with the zebrin II compartment maps from the same individuals, the V1 receptive field was centered on P1-, V2 on P2-, and V3 on P3-. However, the receptive fields typically extended beyond the P- band into the neighboring P+ to each side. Thus there is a simple, reproducible vibrissal receptive field organization in lobule IXa that bears a constant relationship to the Purkinje cell compartmentation revealed by zebrin II immunocytochemistry. The biochemical parcellation of the cortex may serve to organize the afferent and efferent projection topography and thus to align the sensory and motor maps in the cerebellum.

Animals↗
PubMed1995

Molecular compartmentation expressed in cerebellar cultures in the absence of neuronal activity and neuron-glia interactions.

The purpose of the study was to determine if zebrin compartmentation developed in permanently isolated cerebellar cultures, in the presence of agents that block neuronal activity and in the absence of myelination and astrocytic ensheathment of Purkinje cells. Parasagittally oriented organotypic cultures derived from newborn mice and carefully undercut at explantation to exclude extracerebellar afferents were subjected to three conditions: 1) Some were maintained in standard nutrient medium; 2) some were chronically exposed to tetrodotoxin and elevated levels of magnesium to block neuronal activity; and 3) some were exposed to cytosine arabinoside for the first 5 days in vitro (DIV) to destroy granule cells and oligodendrocytes and functionally compromise astrocytes, so that the astrocytic survivors did not ensheath Purkinje cells. Cultures fixed as whole-mount preparations were reacted with antibody to zebrin II. Cultures that were cryostat sectioned were dually reacted with antibody to zebrin II and calbindin. Groups of zebrin+ and zebrin- Purkinje cells were evident after 14 DIV in all of the experimental conditions, indicating that zebrin compartmentation developed 1) in isolated cerebellar explants, 2) in the absence of neuronal activity, and 3) in the absence of neuron-glia interactions such as myelination and glial ensheathment of Purkinje cell somata and dendrites. These results are consistent with the concept that expression of the zebrin+ and zebrin- phenotypes is an intrinsic property of Purkinje cells. The fact that zebrin expression seems to depend on an intrinsic program of differentiation in Purkinje cells suggests some role for zebrin compartmentation in cerebellar function.

Animals↗
PubMed2004

Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes.

Differences in the composition of the hepatitis C virus (HCV) quasispecies between plasma and blood mononuclear cells (BMC) strongly suggest that BMCs support viral replication. We examined the frequency of such compartmentalization, the cell types involved, the constraints exerted on the different variants, and the role of immunoglobulin-complexed variants. We screened the hypervariable region (HVR1) of HCV isolates from 14 HBsAg- and HIV-seronegative patients with chronic HCV infection. HCV RNA was amplified and cloned from plasma, the immunoglobulin G (IgG)-bound fraction, and total and sorted BMCs (CD19+, CD8+, CD4+, and CD14+ cells). Compartmentalization was estimated using a matrix correlation test. The ratio of nonsynonymous/synonymous substitutions (d(N)/d(S) ratio) was calculated for each compartment. HCV RNA was detected in 3/3 BMC, 11/11 CD19+, 10/11 CD14+, 4/11 CD8+ and 0/11 CD4+ cell samples. HVR1 sequences were significantly different between plasma and at least one cellular compartment in all nine cases analyzed, and between B cells (CD19+) and monocytes (CD14+) in all five available cases. IgG-bound variants were distinct from cellular variants. D(N)/d(S) ratios were similar (n = 3) or lower (n = 6) in cellular compartments compared with plasma and the IgG-bound fraction. In conclusion, HCV compartmentalization is a common phenomenon. B cells and monocytes harbor HCV variants showing a low rate of nonsynonymous mutations, a feature that might contribute to the persistence of HCV infection.

Adult↗
PubMed1984

Retinoic acid alters subcellular compartmentalization of ATP pools in 3T3 cells but not in HeLa cells.

Retinoic acid (RA; beta-all-trans) inhibits the proliferation of both murine 3T3 cells and human HeLa cells. Flow cytometric analyses of exponentially growing cultures show that 3T3 cells are inhibited during the S phase of their cell cycle, while HeLa cells show only a small increase in G1 phase cells. RA (10 microM) causes a 50% increase in total cellular adenosine triphosphate (ATP) pools of 3T3 cells, but not of HeLa cells. We have previously demonstrated that the effects of RA on cellular ATP pools of 3T3 cells are directly related to its inhibition of cellular growth, and now report data which provide a biochemical basis for this process. Established procedures were utilized to investigate the effects of RA on the functional compartmentalization of the nuclear ATP pool which serves as a precursor for RNA synthesis in these cells, and which is shown to be a small pool in comparison with cytoplasmic ATP pools. Expansion of total cellular ATP pools by 1 mM of exogenously supplied unlabeled adenosine is ineffective in reducing the subsequent incorporation of [3H]adenosine into RNA of 3T3 cells. Similar treatment of HeLa cells yields a modest reduction in the incorporation of [3H]adenosine into RNA. RA treatment of HeLa cells does not affect the preferential uptake of exogenous [3H] adenosine into the immediate precursor ATP pool for RNA synthesis. RA treatment of 3T3 cells markedly reduces the incorporation of [3H] adenosine into RNA, indicating a lesser degree of functional compartmentalization of the nuclear ATP pool. Similar conclusions are drawn from correlations of the specific radioactivities of total cellular [3H] ATP pools and the levels of incorporation of radioactive label into cellular RNA. In addition, pulse-chase experiments show that RA-treated 3T3 cells continue to incorporate radioactive label from pools prelabeled with [3H]adenosine despite the presence of a large excess of unlabeled adenosine in the chase medium. Control 3T3 and both control and RA-treated HeLa cells cease to incorporate label immediately upon the start of the chase, suggesting that the functional precursor ATP pool for RNA synthesis is small and readily diluted. These data suggest that RA decreases the degree of functional compartmentalization for 3T3, but not HeLa cell ATP pools, and provides a probable mechanism for expansion of nuclear ATP pools of 3T3 cells. The expanded nuclear ATP pools may provide the biochemical mechanism for the inhibition of DNA synthesis during the S phase of the 3T3 cell cycle.

Adenosine↗
PubMed2001

Studies of metabolic compartmentation and glucose transport using in vivo MRS.

Organs consist of several types of cells with specialized functions. This cellular localization of function is often referred to as compartmentation. Due to the intrinsic low sensitivity of MR methods it is generally not possible in vivo to obtain images or spectra of single cells. Instead the MRS signal is the sum of the signal from millions of cells and multiple cell types. A major challenge in using MRS to study biological processes such as metabolism and transport is to devise measurements that provide cell-specific information from this mix. Fortunately nature has helped the MR scientist by in several cases nearly completely localizing metabolic pathways and their associated metabolites in specific cell types. The chemical specificity of MRS allows the concentrations and synthesis rates of these metabolites to be measured, providing information about the compartmentation of metabolism and function. In this review examples are presented from MRS studies of metabolic trafficking between neurons and astrocytes in the brain, brain glucose transport, and the role of muscle glucose transport in insulin resistance and diabetes. The concepts and approaches used in these studies are generally applicable for studying cellular metabolic compartmentation in a wide range of systems.

Astrocytes↗
PubMed2004

Compartmentation of glycolysis and glycogenolysis in the perfused rat heart.

Developing methods that can detect compartmentation of metabolic pathways in intact tissues may be important for understanding energy demand and supply. In this study, we investigated compartmentation of glycolysis and glycogenolysis in the isolated perfused rat heart using (13)C NMR isotopomer analysis. Rat hearts previously depleted of myocardial glycogen were perfused with 5.5 mm [U-(13)C]glucose plus 50 mU/mL insulin until newly synthesized glycogen recovered to new steady-state levels ( approximately 60% of pre-depleted values). After a short wash-out period, the perfusate glucose was then switched to [1-(13)C]glucose, and glycolysis and glycogenolysis were stimulated by addition of glucagon (1 microg/ml). A (13)C NMR multiplet analysis of the methyl resonance of lactate provided an estimate of pyruvate derived from glucose vs glycogen while a multiplet analysis of the C4 resonance of glutamate provided an estimate of acetyl-CoA derived from glycolytic pyruvate vs glycogenolytic pyruvate. These two indices were not equivalent and their difference was further magnified in the presence of insulin during the stimulation phase. These combined observations are consistent with functional compartmentation of glycolytic and glycogenolytic enzymes that allows pyruvate generated by these two processes to be distinguished at the level of lactate and acetyl-CoA.

Animals↗
PubMed1998

Compartmental models: theory and practice using the SAAM II software system.

Understanding in vivo the functioning of metabolic systems at the whole-body or regional level requires one to make some assumptions on how the system works and to describe them mathematically, that is, to postulate a model of the system. Models of systems can have different characteristics depending on the properties of the system and the database available for their study; they can be deterministic or stochastic, dynamic or static, with lumped or distributed parameters. Metabolic systems are dynamic systems and we focus here on the most widely used class of dynamic (differential equation) models: compartmental models. This is a class of models for which the governing law is conservation of mass. It is a very attractive class to users because it formalizes physical intuition in a simple and reasonable way. Compartmental models are lumped parameter models, in that the events in the system are described by a finite number of changing variables, and are thus described by ordinary differential equations. While stochastic compartment models can also be defined, we discuss here the deterministic versions--those that can work with exact relationships between model variables. These are the models most widely used in discussions of endocrinology and metabolism. In this chapter, we will discuss the theory of compartmental models, and then discuss how the SAAM II software system, a system designed specifically to aid in the development and testing of multicompartmental models, can be used.

Blood Glucose↗
PubMed1989

Pattern of compartmentation in human seminiferous tubules showing dislocation of spermatogonia.

The pattern of compartmentation of the seminiferous epithelium was investigated, using a lanthanum tracer technique, in human testicular biopsies of adult infertile men (age 27 to 44 years), where dislocation of spermatogonia from the basal lamina occurred. Spermatogonia type A and B were found in a two- or three-layered arrangement, in aberrant locations throughout the seminiferous epithelium, and in intratubular positions associated with fragments of Sertoli cell cytoplasm. Tracer impregnation was found around spermatogonia in a multilayered arrangement, indicating the extension of the basal compartment in a luminal direction. Single spermatogonia within the second or third layer of the seminiferous epithelium were regularly found to be surrounded by tracer. The junctional complex between the lateral membranes of adjacent Sertoli cells was devoid of tight junctions. Tracer penetration around spermatogonia in a more luminal position was prevented by intact Sertoli cell junctional complexes; tracer was also absent from intraluminal located spermatogonia associated with cytoplasmic fragments of Sertoli cells. The luminal extension of the basal compartment associated with the dislocation of spermatogonia clearly differs from the pattern of compartmentation during the movement of primary spermatocytes within undisturbed epithelium. There is a strong incidence of elevated serum levels of follicle-stimulating hormone (greater than 7 U/l), indicating a suppression of Sertoli cell function; this may be the cause for the dislocation of spermatogonia and the changes of compartmentation.

Adult↗
PubMed1986

Compartmentation of newly synthesized phosphatidylethanolamine in rat brain microsomes.

The compartmentation of the phosphatidylethanolamine newly synthesized in brain microsomes in vitro either by base exchange or net synthesis has been studied, using difluorodinitrobenzene as a chemical probe. The experimental results demonstrate that in rat brain microsomes the phosphatidylethanolamine molecules synthesized by base exchange and the bulk membrane lipid belong to different pools. Ca2+ bound to microsomes seems to be involved in the maintenance of the compartmentation of phosphatidylethanolamine. In the presence of Ca2+ the newly synthesized phosphatidylethanolamine molecules react with difluorodinitrobenzene as though they are organized in clusters. After biosynthesis in vivo or in vitro through the cytidine pathway, the compartmentation of the newly formed phosphatidylethanolamine appears less marked than after the synthesis through base exchange.

Animals↗
PubMed1989

Resistances and compliances of a compartmental model of the cerebrovascular system.

A lumped parameter compartmental model for the nonsteady flow of the cerebrovascular fluid is constructed. The model assumes constant resistances that relate fluid flux to pressure gradients, and compliances between compartments that relate fluid accumulation to rate of pressure changes. Resistances are evaluated by using mean values of artery and cerebrospinal fluid (CSF) fluxes and mean compartmental pressures. Compliances are then evaluated from clinical data of simultaneous pulse wave recordings in the different compartments. Estimate of the average CSF compartmental deformation, based on the compliance between the CSF and brain tissue compartments, proves to be of the order of magnitude of actual experimental measurements.

Blood-Brain Barrier↗
PubMed2006

Within-patient variation of the pharmacokinetics of subcutaneously injected biphasic insulin aspart as assessed by compartmental modelling.

AIMS/HYPOTHESIS: Pharmacokinetics of s.c. administered insulin preparations have been widely studied, mostly using descriptive measures such as AUC, time to peak, or the peak plasma concentration. Several compartmental modelling studies of single-bolus s.c. insulin pharmacokinetics have also appeared, with contrasting results regarding the feasibility of insulin pharmacokinetics modelling and the appropriate level of detail for such models. In this paper, we used compartmental models to study the pharmacokinetics of biphasic insulin aspart administered by multiple s.c. injections. The main objective was to assess the magnitude of the inter-and intra-subject variation in the kinetics. MATERIALS AND METHODS: Analyses were performed on 24-h serum insulin concentrations measured in 20 type 1 diabetes subjects given three daily s.c. injections of biphasic insulin aspart. RESULTS: Preliminary analysis of the AUC:dose ratio showed that the apparent kinetics are not constant throughout the three daily injections of the compound. A simple and robust compartmental model was shown to be appropriate for interpreting the observations, provided that one of its parameters (the first-order rate constant for transfer from the s.c. depot to plasma) is allowed to vary between injections. CONCLUSIONS/INTERPRETATION: Population estimates of the chosen model show that intra-subject variations between injections is of the same order of magnitude as inter-subject variation, partially explaining the difficulties encountered when individually tailoring intensified insulin therapy. We conclude that the explicit consideration of a rather simple kinetic model will allow better experimental designs in the future study of s.c. insulin preparations.

Area Under Curve↗
PubMed2000

Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-alpha.

OBJECTIVES: To determine the effect on compartmentalization of the tumor necrosis factor (TNF)-alpha response in the lung and systemically after ventilation with high peak inspiratory pressure with and without positive end-expiratory pressure (PEEP). DESIGN AND SETTING: Prospective, randomized, animal study in an experimental laboratory of a university. SUBJECTS AND INTERVENTIONS: 85 male Sprague-Dawley rats. Lipopolysaccharide was given intratracheally or intraperitoneally to stimulate TNF-alpha production; control animals received a similar amount of saline. Animals were subsequently ventilated for 20 min in a pressure control mode with peak inspiratory pressure/PEEP ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E ratio 1:2, FIO2 = 1). MEASUREMENTS AND RESULTS: Blood gas tension and arterial pressures were recorded at 1, 10, and 20 min after start of mechanical ventilation. After killing of the animals pressure-volume curves were recorded, and bronchoalveolar lavage (BAL) was performed for assessment of protein content and the small/large surfactant aggregate ratio. TNF-alpha was determined in serum and BAL. TNF-alpha levels were significantly increased after lipopolysaccharide stimulation; furthermore ventilation without PEEP resulted in a significant shift of TNF-alpha to the nonstimulated compartment as opposed to ventilation with a PEEP level of 10 cmH2O. CONCLUSIONS: Ventilation strategies which are known to induce ventilation-induced lung injury (VILI) disturb the compartmentalization of the early cytokines response in the lung and systemically. Furthermore, the loss of compartmentalization is a two-way disturbance, with cytokines shifting from the vascular side to the alveolar side and vice versa. A ventilation strategy (PEEP level of 10 cmH2O) which prevents VILI significantly diminished this shift in cytokines.

Analysis of Variance↗
PubMed2006

Upper extremity compartmental anatomy: clinical relevance to radiologists.

Malignant tumors of the upper extremity are uncommon, and their care should be referred to specialized facilities with experience treating these lesions. The Musculoskeletal Tumor Society (MSTS) staging system is used by the surgeon to determine appropriate surgical management, assess prognosis, and communicate with other healthcare providers. Magnetic resonance imaging (MRI) is employed pre-operatively to identify a lesion's compartment of origin, determine extent of spread, and plan biopsy and resection approaches. Involvement of neurovascular structures may result in devastating loss of upper extremity function, requiring amputation. Violation of high-resistance compartmental barriers necessitates more extensive surgical resection. Biopsy may be performed by the radiologist using imaging guidance. Knowledge of compartmental anatomy allows the radiologist or surgeon to use an easily excisable biopsy approach and prevent iatrogenic spread to unaffected compartments. Case examples are presented to illustrate the importance of compartmental anatomy in the management of benign and malignant upper extremity tumors.

Bone Neoplasms↗