22,359 research outputs found
Active regulation of the epidermal calcium profile
A distinct calcium profile is strongly implicated in regulating the multi-layered structure of the epidermis. However, the mechanisms that govern the regulation of this calcium profile are currently unclear. It clearly depends on the relatively impermeable barrier of the stratum corneum (passive regulation) but may also depend on calcium exchanges between keratinocytes and extracellular fluid (active regulation). Using a mathematical model that treats the viable sublayers of unwounded human and murine epidermis as porous media and assumes that their calcium profiles are passively regulated, we demonstrate that these profiles are also actively regulated. To obtain this result, we found that diffusion governs extracellular calcium motion in the viable epidermis and hence intracellular calcium is the main source of the epidermal calcium profile. Then, by comparison with experimental calcium profiles and combination with a hypothesised cell velocity distribution in the viable epidermis, we found that the net influx of calcium ions into keratinocytes from extracellular fluid may be constant and positive throughout the stratum basale and stratum spinosum, and that there is a net outflux of these ions in the stratum granulosum. Hence the calcium exchange between keratinocytes and extracellular fluid differs distinctly between the stratum granulosum and the underlying sublayers, and these differences actively regulate the epidermal calcium profile. Our results also indicate that plasma membrane dysfunction may be an early event during keratinocyte disintegration in the stratum granulosum
Determination of extracellular fluid volume in healthy and azotemic cats
BACKGROUND: Methods for determining extracellular fluid volume (ECFV) are important clinically for cats. Bromide dilution has been studied in cats to estimate ECFV. Markers of GFR also distribute in ECFV and can be used for its measurement. HYPOTHESIS/OBJECTIVES: The primary objective was to develop a method of determining ECFV from iohexol clearance in cats and evaluate agreement with that determined using bromide dilution. Additional objectives were to compare ECFV between azotemic and nonazotemic cats and evaluate appropriate methods of standardizing ECFV. ANIMALS: Client‐owned cats with varying renal function. METHODS: Validation of ECFV determined from slope‐intercept iohexol clearance was performed in 18 healthy nonazotemic cats. ECFV was then determined using the validated method and bromide dilution and agreement assessed. Appropriateness of standardization to body weight (BW) and body surface area (BSA) was evaluated. RESULTS: Extracellular fluid volume determined from slope‐intercept iohexol clearance and bromide dilution was 0.84 ± 0.32 L and 0.85 ± 0.19 L (mean ± SD), respectively. There were wide limits of agreement between the methods (−0.58 to 0.54 L) and therefore, agreement was considered to be poor. ECFV did not differ significantly between azotemic and nonazotemic cats (P = .177). BSA was found to be the best method for standardizing ECFV measurement in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: This study developed a method for determining ECFV from slope‐intercept iohexol clearance which provides simultaneous assessment of renal function and an estimate of ECFV. ECFV does not differ between azotemic and nonazotemic cats, which suggests fluid volume loss or overload is not an important clinical feature in cats with mild chronic kidney disease
Parathyroid hormone and calcitonin regulating calcium levels
Maintaining normal calcium levels within the body (8.5-10 mg dL -1) requires the action of two hormones in particular: Parathyroid Hormone (PTH) and calcitonin (http://www.bloodbook.com/ranges.html). In lower calcium levels, PTH is released and works in such a way as to increase the calcium back to the normal range. Calcitonin acts exactly in the inverse way by targeting osteoclasts and osteoblasts. A somewhat constant amount of calcium is lost from the body through fecal excretion. In the gut, absorption and secretion of calcium and phosphate occurs, depending on the free ionized calcium in the extracellular fluid. The amount of calcium in the extracellular fluid also influences excretion of calcium in the renal system. The largest pool of calcium is found in bone which is essential in calcium homeostasis. This is because through bone remodelling, calcium may be taken up from the extracellular fluid or given up to the extracellular fluid depending on the presence of hormones in a process known as osteolytic osteolysis. The processes mentioned before are mediated through PTH, calcitonin and 1,25-dihydroxycholecalciferol.peer-reviewe
In vivo monitoring of neuronal loss in traumatic brain injury: a microdialysis study
Traumatic brain injury causes diffuse axonal injury and loss of cortical neurons. These features are well recognized histologically, but their in vivo monitoring remains challenging. In vivo cortical microdialysis samples the extracellular fluid adjacent to neurons and axons. Here, we describe a novel neuronal proteolytic pathway and demonstrate the exclusive neuro-axonal expression of Pavlov’s enterokinase. Enterokinase is membrane bound and cleaves the neurofilament heavy chain at positions 476 and 986. Using a 100 kDa microdialysis cut-off membrane the two proteolytic breakdown products, extracellular fluid neurofilament heavy chains NfH476−986 and NfH476−1026, can be quantified with a relative recovery of 20%. In a prospective clinical in vivo study, we included 10 patients with traumatic brain injury with a median Glasgow Coma Score of 9, providing 640 cortical extracellular fluid samples for longitudinal data analysis. Following high-velocity impact traumatic brain injury, microdialysate extracellular fluid neurofilament heavy chain levels were significantly higher (6.18 ± 2.94 ng/ml) and detectable for longer (>4 days) compared with traumatic brain injury secondary to falls (0.84 ± 1.77 ng/ml, <2 days). During the initial 16 h following traumatic brain injury, strong correlations were found between extracellular fluid neurofilament heavy chain levels and physiological parameters (systemic blood pressure, anaerobic cerebral metabolism, excessive brain tissue oxygenation, elevated brain temperature). Finally, extracellular fluid neurofilament heavy chain levels were of prognostic value, predicting mortality with an odds ratio of 7.68 (confidence interval 2.15–27.46, P = 0.001). In conclusion, this study describes the discovery of Pavlov’s enterokinase in the human brain, a novel neuronal proteolytic pathway that gives rise to specific protein biomarkers (NfH476−986 and NfH476−1026) applicable to in vivo monitoring of diffuse axonal injury and neuronal loss in traumatic brain injury
Multiphase modelling of tumour growth and extracellular matrix interaction: mathematical tools and applications
Resorting to a multiphase modelling framework, tumours are described here as a mixture of tumour and host cells within a porous structure constituted by a remodelling extracellular matrix (ECM), which is wet by a physiological extracellular fluid. The model presented in this article focuses mainly on the description of mechanical interactions of the growing tumour with the host tissue, their influence on tumour growth, and the attachment/detachment mechanisms between cells and ECM. Starting from some recent experimental evidences, we propose to describe the interaction forces involving the extracellular matrix via some concepts coming from viscoplasticity. We then apply the model to the description of the growth of tumour cords and the formation of fibrosis
Multiphase modeling and qualitative analysis of the growth of tumor cords
In this paper a macroscopic model of tumor cord growth is developed, relying
on the mathematical theory of deformable porous media. Tumor is modeled as a
saturated mixture of proliferating cells, extracellular fluid and extracellular
matrix, that occupies a spatial region close to a blood vessel whence cells get
the nutrient needed for their vital functions. Growth of tumor cells takes
place within a healthy host tissue, which is in turn modeled as a saturated
mixture of non-proliferating cells. Interactions between these two regions are
accounted for as an essential mechanism for the growth of the tumor mass. By
weakening the role of the extracellular matrix, which is regarded as a rigid
non-remodeling scaffold, a system of two partial differential equations is
derived, describing the evolution of the cell volume ratio coupled to the
dynamics of the nutrient, whose higher and lower concentration levels determine
proliferation or death of tumor cells, respectively. Numerical simulations of a
reference two-dimensional problem are shown and commented, and a qualitative
mathematical analysis of some of its key issues is proposed.Comment: 34 pages, 18 figure
Macroscopic models of local field potentials and the apparent 1/f noise in brain activity
The power spectrum of local field potentials (LFPs) has been reported to
scale as the inverse of the frequency, but the origin of this "1/f noise" is at
present unclear. Macroscopic measurements in cortical tissue demonstrated that
electric conductivity (as well as permittivity) is frequency dependent, while
other measurements failed to evidence any dependence on frequency. In the
present paper, we propose a model of the genesis of LFPs which accounts for the
above data and contradictions. Starting from first principles (Maxwell
equations), we introduce a macroscopic formalism in which macroscopic
measurements are naturally incorporated, and also examine different physical
causes for the frequency dependence. We suggest that ionic diffusion primes
over electric field effects, and is responsible for the frequency dependence.
This explains the contradictory observations, and also reproduces the 1/f power
spectral structure of LFPs, as well as more complex frequency scaling. Finally,
we suggest a measurement method to reveal the frequency dependence of current
propagation in biological tissue, and which could be used to directly test the
predictions of the present formalism
Model of Low-pass Filtering of Local Field Potentials in Brain Tissue
Local field potentials (LFPs) are routinely measured experimentally in brain
tissue, and exhibit strong low-pass frequency filtering properties, with high
frequencies (such as action potentials) being visible only at very short
distances (10~) from the recording electrode. Understanding
this filtering is crucial to relate LFP signals with neuronal activity, but not
much is known about the exact mechanisms underlying this low-pass filtering. In
this paper, we investigate a possible biophysical mechanism for the low-pass
filtering properties of LFPs. We investigate the propagation of electric fields
and its frequency dependence close to the current source, i.e. at length scales
in the order of average interneuronal distance. We take into account the
presence of a high density of cellular membranes around current sources, such
as glial cells. By considering them as passive cells, we show that under the
influence of the electric source field, they respond by polarisation, i.e.,
creation of an induced field. Because of the finite velocity of ionic charge
movement, this polarization will not be instantaneous. Consequently, the
induced electric field will be frequency-dependent, and much reduced for high
frequencies. Our model establishes that with respect to frequency attenuation
properties, this situation is analogous to an equivalent RC-circuit, or better
a system of coupled RC-circuits. We present a number of numerical simulations
of induced electric field for biologically realistic values of parameters, and
show this frequency filtering effect as well as the attenuation of
extracellular potentials with distance. We suggest that induced electric fields
in passive cells surrounding neurons is the physical origin of frequency
filtering properties of LFPs.Comment: 10 figs, revised tex file and revised fig
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