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At least 865 records · Page 48Linked to original sources
PubMed1994

Water transport across biological membranes.

The rate of the lateral diffusion of straight-chain phospholipids predicts the rate of water diffusion through bilayers. A new model of lipid dynamics integrates these processes. Substances such as cholesterol that reduce water diffusion proportionally reduce lateral diffusion. The model yields a number of predictions about the dynamics of the lipids at the Tm and suggests different mechanisms for how water diffuses across bilayers of other-than-straight-chain lipids, and how proteins bind to membranes. A second recent development in water transport across biological membranes is the discovery of a ubiquitous family of water transport proteins that facilitate large-volume water translocation. Like water diffusion through lipid bilayers, water transport by these proteins is directed by osmosis and is therefore under the control of ATP and ion pumps. The presence of water transport proteins in membranes is often regulated by hormones.

Biological Transport↗
PubMed1993

Two-layer membrane model for iontophoretic drug transport through excised rat skin.

Iontophoretic and passive transport of an ionized drug (sulfisoxazole) across excised rat skin was studied using a two-chamber cell with four electrodes under successive experimental conditions: without electrical current (stage-I) and with electrical current (stage-II). Two iontophoretic/diffusion models, i.e. a one-layer membrane model and a two-layer membrane model, in which a difference in the electrical potential gradient was taken into account between the stratum corneum and epidermis/dermis layer, were constructed to describe the non-steady-state drug permeation process during ionotrophoresis. The observed iontophoretic lag-time was two times greater than the calculated value based on the one-layer membrane model. According to the two-layer membrane model, the calculated ionotophoretic lag-time agreed with the observed value. It was revealed by model adaptation to the observed data that the stratum corneum fraction of the electro-chemical potential difference across the whole skin caused by the iontophoresis was around 90%. This result was consistent with the observation that the direct current resistance of whole skin was seven times greater than that of stripped skin.

Animals↗
PubMed2006

Evaluation of HO-1-u-1 cell line as an in vitro model for sublingual drug delivery involving passive diffusion--Initial validation studies.

The aim of this study was to provide preliminary validation of a new sublingual mucosal cell line (HO-1-u-1) for use as in vitro sublingual drug delivery screening of compounds involving passive diffusion. HO-1-u-1 cells were seeded on cell culture inserts. The ultrastructure and integrity of cell layers, inter-passage variation and directionality of drug transport, and apparent permeability coefficient (P(app)) of eight beta-blockers (representing compounds involving passive diffusion) were determined. HO-1-u-1 cells grown on inserts formed stratified and epithelial-like structure and maintained the typical histological features of normal human sublingual epithelium. The maximal integrity of the cell layer was reached in 23 days. No significant inter-passage variation was found at the passages ranging from 2 to 11 when measured by radiolabeled transcellular and paracellular markers (testosterone and mannitol, respectively). Bidirectional transport studies confirmed the passive diffusion as the mechanism of transport for these markers. The P(app) of eight beta-blockers across HO-1-u-1 cell culture ranged from 2.89+/-0.17 to 6.37+/-0.37x10(-6)cm/s and correlated well to the P(app) obtained from porcine sublingual mucosa (r(2)=0.647 and 0.83 when excluding propranolol). The above results indicate that the HO-1-u-1 cells grown on inserts may offer as a potentially in vitro model for screening sublingual drug permeation involving passive diffusion.

Administration, Sublingual↗
PubMed2004

Combining geometrical and dynamical disorder to enhance transport.

We look for the optimal way to distribute rectifiers in order to maximize their effect on the transport properties of Brownian particles. These rectifiers are introduced in the form of flashing asymmetric potentials distributed on a one dimensional lattice. We study the effects that different distributions of these rectifiers have on the generated current and on the energy cost of transport. Based on both analytical and numerical results, we observe an unexpected increase in the efficiency of the rectifiers and the magnitude of the current for the case in which geometrical and dynamical disorder are combined. We show that this effect is a direct consequence of the "hitchhiker" or "waiting time" paradox.

Biological Transport↗
PubMed2006

Modelling the dynamic air-water-sediment coupled fluxes and occurrence of polychlorinated biphenyls in a high altitude lake.

The BIODEP model in terms of atmosphere-lake interactions was developed. The model was applied to an oligotrophic, dimictic high altitude lake (Lake Redo, Pyrenees) for a range of polychlorinated biphenyl (PCB) congeners. High altitude lakes, which receive their contaminant inputs uniquely from the atmosphere through long-range atmospheric transport, provide ideal controlled environments for the study of the interactions between atmospheric depositional and water column biogeochemical processes. The BIODEP model was able to predict dissolved water concentrations and PCB accumulation in the lake sediment within a factor of 2. This shows that the BIODEP model captures the essential processes driving the sink of POPs in high altitude lakes and that POP occurrence in the lake is driven by direct atmospheric inputs with limited influence from the watershed. An important seasonal variability in water column concentrations is predicted which should have important implications in sampling strategies. Furthermore, it is shown that diffusive air-water exchange dominated the PCB dynamics in the lake, especially for the less chlorinated biphenyls.

Air↗
PubMed1998

Protein mediated magnetic coupling between lactate and water protons.

The magnetic coupling between methyl lactate protons and water protons in samples of cross-linked bovine serum albumin (BSA) is studied. Cross-relaxation spectroscopy shows efficient magnetization transfer from immobilized BSA to both water and methyl lactate protons. Transient and steady-state NOE experiments reveal a negative intermolecular NOE between methyl lactate and water protons. Lactate is indirectly detected by selectively saturating the methyl lactate protons and measuring the decrease in water proton magnetization. Indirect detection of methyl lactate protons is an order of magnitude more sensitive than direct detection in these model systems. Lactate was indirectly imaged, via the water proton resonance, with 1.1-microliter voxels in 2 min. Immobilized BSA reduces the intermolecular correlation time between water and lactate protons into the spin-diffusion limit where the NOE is negative. Possible molecular mechanisms for this coupling and applications to in vivo spectroscopy are discussed.

Animals↗
PubMed1976

Facilitated transport of di- and trinitrophenolate ions across lipid membranes by valinomycin and nonactin.

The conductance of black lipid membranes in the presence of 2,4,6-trinitrophenol (or 2,4-dinitrophenol) is considerably enhanced, if the cation carriers valinomycin, enniatin B or nonactin are added. The effect is, however, largely independent of the cation concentration and is identical for the cations Li+, Na+ and Ba2+. This finding, as well as the sign and magnitude of the diffusion potential in the presence of a gradient of picrate are consistent with the assumption that the transport of picrate anions is facilitated by the above-mentioned macrocyclic compounds, but that cations are not directly involved. A model is suggested which, based on the generation of mobile defect structures by the incorporation of large molecules, allows one to explain facilitated transport without the assumption of stable chemical bonds between a carrier and its transported substrate. If K+ is present in the aqueous phase, the conductance is largely determined by the permeation of the cation complexes of valinomycin and nonactin. The conductance is, however, increases by adsorption of picrate anions to the membrane surface. The negative surface potential generated by the adsorption layer seems to be responsible for the saturation of the conductance at high picrate concentrations in the absence of valinomycin and nonactin.

Anti-Bacterial Agents↗
PubMed1992

A distributed model of exchange processes within the osteon.

In order to understand various exchange processes within the osteon, a mathematical model to describe the system has been developed which allows for concentration gradients in the axial and radial directions as well as cellular consumption and binding to bone surface. The normal values for the model parameter are discussed and the effects of the model parameters on the behaviour of the model are investigated. This model supports the idea that diffusion alone may be an inefficient mechanism in transport between blood and osteocytes.

Biological Transport↗
PubMed1988

A physiologically based model of skeletal growth in the rat.

A model of the growing small animal skeleton has been developed. The model accurately reproduces a variety of different kinds of measurements made at different ages in different species, as well as reproducing a precise and detailed series of measurements in the growing guinea pig. Of the multiple mechanisms responsible for transfer of bone-seeking elements from blood to bone and back again, several are quantitatively insignificant on a skeletal scale. Surface (rapid) exchange, diffuse (slow) exchange, and secretion of new bone during growth are the principal determinants of skeletal metabolism. Bone blood flow can probably by satisfactorily modeled as a combination of a basal flow rate plus an increment that is directly proportional to formation rate of new bone.

Age Factors↗
PubMed1993

Ca2+ channel blocking activity of lacidipine and amlodipine in A7r5 vascular smooth muscle cells.

Inhibition of the K(+)-stimulated increase in cytosolic free Ca2+ by a series of 1,4-dihydropyridines was evaluated in A7r5 vascular smooth muscle cells loaded with the fluorescent Ca2+ indicator fura-2 acetoxymethyl ester. The IC50 of the drugs, added to suspended cells 3 min before 150 mM KCl, gave the following order of potency: lacidipine (2.76 nM) > nitrendipine (3.81 nM) > amlodipine (4.56 nM) > nifedipine (10.08 nM). A7r5 cells were also exposed to the 1,4-dihydropyridines, at their IC50, for 25 min, and then repeated washout cycles were performed before adding KCl. The Ca2+ channel blocking activity of nifedipine and nitrendipine gradually diminished, disappearing after four washout cycles 25, 55, 115 and 175 min after drug treatment. Amlodipine and lacidipine displayed slow onset and offset of antagonism, their activity becoming stronger with time, in spite of the repeated washes. [3H]Lacidipine was avidly and promptly entrapped in A7r5 cells and was not removed by washout. However, its potency as a Ca2+ channel blocker was not directly related to the amount of drug locked in the cell since it increased with time, indicating that lacidipine binds to the lipid bilayer of the cell membrane and then gradually diffuses towards a specific binding site. This model can, therefore, predict the Ca2+ blocking properties of 1,4-dihydropyridines with slow onset and offset of antagonism and could be employed to evaluate compounds selective for vascular smooth muscle.

Amlodipine↗
PubMed2005

Ability of static and statistical mechanics posturographic measures to distinguish between age and fall risk.

Traditional posturographic analysis and four statistical mechanics techniques were applied to center-of-pressure (COP) trajectories of young, older "low-fall-risk" and older "high-fall-risk" individuals. Low-fall-risk older adults were active 3 days per week in a cardiac rehabilitation program, while high-fall-risk older adults were diagnosed with perilymph fistula. Subjects diagnosed with perilymph fistula must have experienced two of the following vestibular findings: constant disequilibrium, positional vertigo and/or a positive fistula test. Non-parametric statistical tests were used to determine whether the posturographic measures could detect differences between the young and older "low-fall-risk" groups (age comparison) and between the older "low-" and "high-risk" groups (risk of falling comparison). The statistical mechanics techniques were more sensitive than the traditional measures: detecting significant differences between the young and older "low-risk" groups, while none of the traditional measures were significantly different. In addition, interpretation of the statistical mechanics techniques may offer more insight into the nature of the process controlling the COP trajectories. However, the methods offered slightly different explanations. For instance, the Hurst rescaled range analysis suggests that the movement of the COP is governed solely by anti-persistent behavior, whereas the stabilogram diffusion analysis suggests a short-term persistence balanced by a long-term anti-persistence. These discrepancies highlight the need for a model that incorporates the biological systems responsible for maintaining balance and experimental methods to directly quantify their status and roles. Until such a model exists, however, the statistical mechanics techniques appear to have some advantages over traditional posturographic measures for studying balance control.

Accidental Falls↗
PubMed1997

Ultrasound attenuation and backscatter in the liver during prednisone administration.

Ultrasound attenuation and backscatter changes resulting from glucocorticoid administration were investigated in a dog model. Ten beagle dogs were randomized into two groups: five were given 2 mg/kg/day IM injections of prednisone to induce steroid hepatopathy and five served as controls. Histology showed vacuolization in most hepatocytes of treated animals on the third day of treatment, and larger, midzonally distributed vacuoles from day 7 on. An increase in both ultrasonic attenuation and backscatter was observed in treated dogs during in vivo measurements. Pooled data from the two groups suggest that attenuation elevations precede backscatter changes. Attenuation was significantly higher in the treated animals than in the controls by day 7. Both attenuation and backscatter were significantly higher in livers of treated than untreated dogs when measured by direct application of the transducer on the liver following euthanasia. We conclude that attenuation and backscatter coefficients can detect early changes in the liver associated with steroid hepatopathy. This may be a useful model to investigate detection of diffuse liver disease with ultrasound tissue characterization.

Animals↗
PubMed1998

Mode of action of site-directed irreversible folate analogue inhibitors of thymidylate synthase.

5,8-Dideazafolate analogues are tight binding but not irreversible inhibitors of thymidylate synthase (TS). However, when a chloroacetyl (ClAc) group is substituted at the N10-position of 2-desamino-2-methyl-5,8-dideazafolate (DMDDF), the resulting compound, ClAc-DMDDF, although still a reversible inhibitor (KI = 3.4 x 10(-3) M), gradually inactivates thyA-TS irreversibly at a rate of 0.37 min-1. The corresponding iodoacetyl derivative alkylated the enzyme somewhat slower (k3 = 0.15 min-1 ) than ClAc-DMDDF but was bound more tightly (KI = 1.4 x 10(-5) M), resulting in a second-order rate constant (k3/KI) of inactivation that was 100-fold greater than that of ClAc-DMDDF. A tryptic digest of the ClAc-DMDDF-inactivated enzyme yielded a peptide on HPLC, which revealed that cysteine-146, the residue at the active site that is intimately involved in the catalytic process, had reacted with ClAc-DMDDF to form a covalent bond. This derivative was confirmed indirectly by Edman analysis and more directly by mass spectrometry. Deoxyuridine 5'-monophosphate, a substrate in the catalytic reaction, protected against inactivation. Similar to previously described Lactobacillus casei TS inhibition studies with sulfhydryl reagents [Galivan, J., Noonan, J., and Maley, F. (1977) Arch. Biochem. Biophys. 184, 336-345], the kinetics of inhibition suggested that complete inhibition occurs on reaction of only one of the two active site cysteines, although sequence and amino acid analysis revealed that iodoacetate and ClAc-DMDDF had reacted with both active site cysteines. These studies demonstrate that a sulfhydryl reactive compound that is directed to the folate binding site of TS may diffuse to the active site cysteine, and form a covalent bond with this residue. How this inhibition comes about is suggested in a stereoscopic view of the ligand when modeled to the known crystal structure of Escherichia coli TS.

Amino Acid Sequence↗
PubMed2001

Emergence of taxis and synergy in angiogenesis.

Angiogenesis, the expansion of the vascular system feeding a tumor, is crucial to both primary tumors long-time growth and for the successful implantation of metastases. We formulate a model that relates the energetic requirements of the cancer cells to the production and diffusion of an angiogenic factor and to the ensuing evolution of neighboring endothelial cells. The model yields predictions for the development of neovascularization and for the increase in the blood flow to the tumor. We show that the directed growth of the vascular net is an emergent property and that therapies targeting different stages of the angiogenic process might have a synergistic effect.

Angiogenesis Inducing Agents↗
PubMed1999

Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin.

Evidence of synergism between combinations of vancomycin and beta-lactam antibiotics against 59 isolates of methicillin-resistant staphylococci (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus) for which vancomycin MICs ranged from 1 to 16 microg/ml were tested by broth microdilution checkerboard, disk diffusion, agar dilution, and time-kill antimicrobial susceptibility tests. The combination of vancomycin and oxacillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxicillin-clavulanate but not for aztreonam. Evidence of synergy correlated directly with vancomycin MICs. The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental endocarditis caused by three clinical isolates of glycopeptide-intermediate-susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in this model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffective for animals infected with HIP5827 or MU50. However, the combination of vancomycin and nafcillin resulted in a mean reduction of 4.52 log10 CFU/g of aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4. 15 log10 CFU/g for animals infected with MU50. Renal abscesses caused by HIP5827 were sterilized significantly better with the combination of vancomycin and nafcillin than by either treatment alone. We conclude that the combination of vancomycin and beta-lactams with antistaphylococcal activity is an effective regimen for the treatment of infections with clinical strains of staphylococci which demonstrate reduced susceptibility to glycopeptides.

Animals↗
PubMed2004

[Histologic and ultrastructural features of cell death both physiological and induced by two different teratogens in branchial arches of mouse embryo].

AIM OF THE STUDY: To observe and compare cell death process both physiological and associated with the administration of two different teratogens (irradiation and retinoic acid) inside cephalic mesectoderm. MATERIAL AND METHODS: Irradiated mice: 2 Gy were administered to E 9 embryos. Retinoic acid: 60 mg/kg were gave to E 8 or E 9 embryos. E 9 - 9.5 and E 10 embryos were removed. E 9 - E 9.5 and E 10 control specimens were collected. We used semi-thin sections and ultra-thin sections observed with transmission electron microscope. RESULTS: The major process is apoptosis, which is increased in experimental embryos compared to control specimens. However, autophagy was observed in retinoic acid-treated embryos, while necrosis can rarely occurs after irradiation. CONCLUSION: If the common process seems to be apoptosis, both teratological models differs owing to their respective secondary features. These differences should be explained by the specific pathogenesis of both teratological agents: ligand-receptor reaction and Hox system disruption in retinoic acid administration, direct aggression against DNA and diffuse cell death process following irradiation. Furthermore, congenital malformations induced by these teratogens are quite different. This can be partially explained by a specific blow of different cellular subpopulations.

Animals↗
PubMed2005

Transport of hydrocarbons from an emplaced fuel source experiment in the vadose zone at Airbase Vaerløse, Denmark.

An emplaced hydrocarbon source field experiment was conducted in the relatively homogeneous sandy geology of the vadose zone at Airbase Vaerløse, Denmark. The source (10.2 l of NAPL) consisted of 13 hydrocarbons (n-, iso- and cyclo-alkanes and aromates) and CFC-113 as a tracer. Monitoring in the 107 soil gas probes placed out to 20 m from the centre of the source showed spreading of all the compounds in the pore air and all compounds were measured in the pore air within a few hours after source emplacement. Seven of the fourteen compounds were depleted from the source within the 1 year of monitoring. The organic vapours in the pore air migrated radially from the source. The CFC-113 concentrations seemed to be higher in the deeper soil gas probes compared with the hydrocarbons, indicating a high loss of CFC-113 to the atmosphere and the lack of degradation of CFC-113. For the first days after source emplacement, the transport of CFC-113, hexane and toluene was successfully simulated using a radial gas-phase diffusion model for the unsaturated zone. Groundwater pollution caused by the vadose zone hydrocarbon vapours was only detected in the upper 30 cm of the underlying groundwater and only during the first 3 months of the experiment. Only the most water-soluble compounds were detected in the groundwater and concentrations decreased sharply with depth (approximately one order of magnitude within 10 cm depth) to non-detect at 30 cm depth. The groundwater table varied more than 1 m within the measurement period. However that did not influence the direction of the groundwater flow. Approximately 7 months after source emplacement the groundwater table rose more than 1 m within 1 month. That did not cause additional pollution of the groundwater.

Chlorofluorocarbons, Ethane↗
PubMed1988

Use of weak acids to determine the bulk diffusion limitation of H+ ion conductance through the gramicidin channel.

The addition of 2 M formic acid at pH 3.75 increased the single channel H+ ion conductance of gramicidin channels 12-fold at 200 mV. Other weak acids (acetic, lactic, oxalic) produce a similar, but smaller increase. Formic acid (and other weak acids) also blocks the K+ conductance at pH 3.75, but not at pH 6.0 when the anion form predominates. This increased H+ conductance and K+ block can be explained by formic acid (HF) binding to the mouth of the gramicidin channel (Km = 1 M) and providing a source of H+ ions. A kinetic model is derived, based on the equilibrium binding of formic acid to the channel mouth, that quantitatively predicts the conductance for different mixtures of H+, K+, and formic acid. The binding of the neutral formic acid to the mouth of the gramicidin channel is directly supported by the observation that a neutral molecule with a similar structure, formamide (and malonamide and acrylamide), blocks the K+ conductance at pH 6.0. The H+ conductance in the presence of formic acid provides a lower bound for the intrinsic conductance of the gramicidin channel when there is no diffusion limitation at the channel mouth. The 12-fold increase in conductance produced by formic acid suggests that greater than 90% of the total resistance to H+ results from diffusion limitation in the bulk solution.

Amides↗