Transport of protein in the abdominal wall during intraperitoneal therapy. I. Theoretical approach.
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Intraperitoneal therapies such as peritoneal dialysis or regional chemotherapy use large volumes of solution within the peritoneal cavity. These volumes increase intraperitoneal hydrostatic pressure (P(ip)), which causes flow of the solution into tissues that surround the cavity. The goal of this paper is to integrate new experimental findings in a rigorous mathematical model to predict protein transport from the cavity into tissue. The model describes non-steady-state diffusion and convection of protein through a deformable porous medium with simultaneous exchange with the microcirculation and local tissue binding. Model parameters are dependent on local tissue pressure, which varies with P(ip). Solute interactions with the tissue in terms of local distribution volume (solute void space), local binding, and retardation relative to solvent flow are demonstrated to be major determinants of tissue concentration profiles and protein penetration from the peritoneal cavity. The model predicts the rate of fluid loss from the cavity to the abdominal wall in dialysis patients to be 94 ml/h, within the observed range of 60-100 ml/h. The model is fitted to published transport data of IgG, and the retardation coefficient f is estimated to be 0.3, which markedly reduces the rate of protein penetration and is far lower than previously published estimates. With the value of f = 0.3, model calculations predict that P(ip) of 4.4 mmHg and dialysis duration of 24 h result in several millimeters of protein penetration into the tissue. (+info)
Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients.
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BACKGROUND: Enhanced oxidative stress in haemodialysis (HD) patients may be considered as a risk factor for accelerated atherosclerosis. Reduced antioxidant defences include impairment in enzyme activities and decreased plasma levels of hydrophilic vitamin C (vit C), and cellular levels of lipophilic vitamin E (vit E). METHODS: We investigated plasma levels of vit C in 19 patients undergoing regular haemodiafiltration (HDF) (mean age 62+/-7 years) and in 1846 healthy elderly subjects (HS) (mean age 69+/-5 years). The contribution of convection and diffusion was determined using paired filtration dialysis (PFD), a modified HDF technique which physically separates convective from diffusive fluxes. Blood samples were collected before and after the HDF session; in addition at 60 min of HDF, samples were drawn from arterial lines (AL) and venous lines (VL), dialysate (D) and ultrafiltrate (UF). Blood levels of total vit C were determined using an HPLC fluorescence method. Markers of oxidative stress were also assessed in both populations as follows: levels of malondialdehyde (MDA) were determined by fluorometric assay, measurements of advanced oxidation protein products (AOPP) and glutathione peroxidase (GSH-Px) activity were performed by spectrophotometric assay, and plasma vit E content was obtained by an HPLC procedure. RESULTS: A significant reduction in plasma vit C level was observed in HDF patients when compared with HS (1.6+/-1.4 microg/ml in HDF vs 6.6+/-3.7 microg/ml in HS; P<0.01). The HDF session was associated with a dramatic reduction in vit C levels (1.87+/-1.57 microg/ml before HDF and 0.98+/-0.68 microg/ml after HDF); at 60 min of HDF, concentrations were as follows: AL=1.35+/-1.27 microg/ml; VL=0.37+/-0.31 microg/ml, D=0.40+/-0.34 microg/ml, UF=1.24+/-1.18 microg/ml; corresponding to a diffusive flux of 271 microg/min and a convective flux of 126 microg/min. Total loss of vit C could be assessed at 66 mg/session (8--230 mg/session). According to this loss of vit C, presence of an oxidative stress was demonstrated in HD population as shown by a significant increase in MDA (1.66+/-0.27 microM in HD vs 0.89+/-0.25 microM in HS; P<0.01) and AOPP (77.5+/-29.3 microM in HD vs 23.5+/-13.2 microM in HS; P<0.01) levels, and a decrease in GSH-Px activity (259.2+/-106.3 U/l in HD vs 661.2+/-92.2 U/l in HS; P<0.01). No change in plasma vit E between both populations (30.7+/-9.1 microM in HD vs 35.3+/-7.34 microM in HS) was observed. CONCLUSIONS: These results suggest that HDF with highly permeable membranes is associated with a significant loss of vit C. Diffusive transport is responsible for two-thirds whereas convective phenomenon accounts for only one-third of this loss. (+info)
Semi-volatile organic compounds at the leaf/atmosphere interface: numerical simulation of dispersal and foliar uptake.
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The behaviour of (semi-)volatile organic compounds at the interface between the leaf surface and the atmosphere was investigated by finite-element numerical simulation. Three model systems with increasing complexity and closeness to the real situation were studied. The three-dimensional model systems were translated into appropriate grid structures and diffusive and convective transport in the leaf/atmosphere interface was simulated. Fenpropimorph (cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine) and Kresoxim-methyl ((E)-methyl-2-methoxyimino-2-[2-(o-tolyloxy-methyl)phenyl] acetate) were used as model compounds. The simulation showed that under still and convective conditions the vapours emitted by a point source rapidly form stationary envelopes around the leaves. Vapour concentrations within these unstirred layers depend on the vapour pressure of the compound in question and on its affinity to the lipoid surface layers of the leaf (cuticular waxes, cutin). The rules deduced from the numerical simulation of organic vapour behaviour in the leaf/atmosphere interface are expected to help in assessing how (semi-)volatile plant products (e.g. hormones, pheromones, secondary metabolites) and xenobiotics (e.g. pesticides, pollutants) perform on plant surfaces. (+info)
Modeling of impact of gas molecular diffusion on nitric oxide expired profile.
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Present descriptions of nitric oxide (NO) transport in the lungs use two compartment models: airway compartment without mixing and alveolar compartment with perfect mixing. These models neglect NO molecular diffusion in the airways. To assess the impact of axial diffusion on expired NO profile, we solved a transport equation that incorporated diffusion, convection, and NO sources in the symmetrical Weibel model of the lung. When NO parameters computed from experimental data with the two compartment models are used in our model as NO sources, simulated end-expired NO is 29-45 and 64-78% of experimental values at expiratory flows of 50 and 2,000 ml/s, respectively. These lower values are because of NO axial diffusion: During expiration, NO back diffusion (opposed to convection) prevents some NO from being expired, so a two- to fivefold increase of airway NO excretion is necessary to simulate end-expired NO consistent with experimental data. We conclude that, insofar as a significant amount of NO is produced in small airways, models neglecting NO axial diffusion underestimate excretion in the airways. (+info)
Spatial distribution of dialysate in patients and its implications to intradialysate diffusion.
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OBJECTIVE: To visualize and quantify the spatial distribution of dialysate in patients on continuous ambulatory peritoneal dialysis (CAPD) and, hence, estimate diffusion times for fluid "pockets" wherever intradialysate concentration gradients may not be dissipated by convective currents. DESIGN: Contrast medium was added to the dialysate of three supine CAPD patients before an exchange prior to computed tomographic (CT) scanning. Spatial information in the CT scanner was then downloaded to other computers and processed to produce impressive three-dimensional models of dialysate distribution using "wire frame technology." RESULTS: Models differed between patients but all demonstrated pooling of dialysate in the paracolic gutters, subphrenic space, and, especially, in the pelvic cavity. Some pockets of fluid were almost isolated. Quantitatively, the models can account for over 80% of the volume of the exchange (2.5 L), displaying an effective area of contact of 913-450 cm2 between parietal peritoneum and dialysate. This amounts to only 11% -21% of the anatomic area, again emphasizing the uneven distribution of dialysate. Ignoring very thin (< 0.1 mm) films of dialysate, the bulk (80%) had mean thicknesses ranging from 1.6 to 1.9 cm. Transcendental equations for bulk diffusion were then applied to these findings to determine a theoretical time for urea of about 2-3 hours to half-saturation, or 5-7 hours to 80% saturation, in the absence of convective currents. CONCLUSIONS: The distribution of dialysate within the peritoneal cavity is very uneven, resulting in long diffusion times in fluid pockets wherever convective currents may be minimal. Hence, intradialysate diffusion should not be ignored when modeling peritoneal dialysis. (+info)
Desiccation tolerance of spermatozoa dried at ambient temperature: production of fetal mice.
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Long-term preservation of mouse sperm by desiccation is economically and logistically attractive. The current investigation is a feasibility study of the preservation of mouse sperm by convective drying in an inert gas (nitrogen). Mouse sperm from the B6D2F1 strain isolated in an EGTA-supplemented Tris-HCl buffer were dried using three different drying rates and were stored for 18-24 h at 4 degrees C. The mean final moisture content was <5% for all the protocols. After intracytoplasmic sperm injection (ICSI), the mean blastocyst formation rates were 64%, 58%, and 35% using the rapid-, moderate-, and slow-drying protocols, respectively. The slow-drying protocol resulted in a rate of development significantly lower than that observed using rapid- and moderate-drying protocols and indicated that a slower drying rate may be detrimental to the DNA integrity of mouse sperm. The transfer of 85 two- or four-cell embryos that were produced using rapidly desiccated sperm resulted in 11 fetuses (13%) on Day 15 compared with the production of 34 fetuses (40%) produced using the transfer of 86 two- or four-cell embryos that were produced using fresh sperm (P < 0.05). The results demonstrate the feasibility of using a convective drying protocol for the successful desiccation of mouse sperm and identifies some of the important parameters required for optimization of the procedure. (+info)
Intracellular convection, homeostasis and metabolic regulation.
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Two views currently dominate experimental approaches to metabolic regulation. The first, let us call it Model 1, assumes that cells behave like a watery bag of enzymes. The alternative Model 2, however, assumes that 3-dimensional order and structure constrain metabolite behavior. A major problem in cell metabolism is determining why essentially all metabolite concentrations are remarkably stable (homeostatic) over large changes in pathway fluxes-for convenience, this is termed the [s] stability paradox. During large-scale transitions from maintenance metabolic rates to maximally activated work, contrasting demands of intracellular homeostasis versus metabolic regulation obviously arise. Data accumulated over the last 3-4 decades now make it clear that the demands of homeostasis prevail: during rest-work transitions, metabolites such as ATP and O(2) are notably and rigorously homeostatic; other intermediates usually do not vary by more than 0.5- to threefold over the resting condition. This impressive homeostasis is maintained despite changes in pathway fluxes that can exceed two orders of magnitude. Classical or Model 1 approaches to this problem can explain metabolite homeostasis, but the mechanisms for each metabolite, each enzyme locus, are necessarily specific. Thus Model 1 approaches basically do not provide a global explanation for the [s] stability paradox. Model 2 takes a different tack and assumes that an intracellular convection system acts as an over-riding 'assist' mechanism for facilitating enzyme-substrate encounter. Model 2 postulates that intracellular movement and convection are powered by macromolecular motors (unconventional myosins, dyneins, kinesin) running on actin or tubulin tracks. For fast and slow muscle fibers, microfilaments are concentrated near the periphery (where convection may be most important), but also extend throughout the actomyosin contractile apparatus both in horizontal and vertical dimensions. To this point in the development of the field, Model 1 and Model 2 approaches have operated as 'two solitudes', each considering the other incompatible with its own experimental modus operandi. In order to finally assemble a model that can sensibly explain a realistic working range of metabolic systems, opening of channels of communication between the above two very differing views of metabolic regulation would seem to be the requirement for the future. (+info)
Ultrarapid, convection-enhanced intravascular hypothermia: a feasibility study in nonhuman primate stroke.
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BACKGROUND AND PURPOSE: Hypothermia has been shown to be neuroprotective in a variety of clinical settings. Unfortunately, poor delivery techniques and insufficient data in appropriate preclinical models have hampered its development in human stroke. To address these limitations, we have devised a 10F intravascular catheter capable of rapid systemic cooling of nonhuman primates. METHODS: Placed in the inferior vena cava via a transfemoral approach, the catheter was used to induce mild systemic hypothermia 3 hours after the onset of hemispheric stroke in baboons. RESULTS: Cooling was achieved at a rate of 6.3+/-0.8 degrees C/h. Target brain temperatures (32.2+/-0.2 degrees C) were reached at the same time (47.7+/-6.32 minutes) as target esophageal temperatures (32.0+/-0.0 degrees C). Hypothermia was maintained for 6 hours in all animals. Animals did not experience the infections, coagulopathy, or cerebral edema commonly seen with surface cooling methods in human stroke. CONCLUSIONS: These data suggest that a brief episode of mild core hypothermia instituted at a clinically relevant time point can be achieved in primate stroke and that our intravascular cooling technique provides safe, rapid, and reproducible hypothermia. (+info)