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[Hyperaluminemia in chronic hemodialysis patients. Evaluation of the respective roles of dialysate aluminum and oral aluminum hydroxide].

UNLABELLED: In order to evaluate the respective role of dialysate aluminium and of oral aluminium hydroxide in the occurrence of hyperaluminemia in patients on chronic hemodialysis, plasma aluminium was measured in 19 of them selected for their reliability, before and then 6 and 12 months after the use of a double step reverse osmosis system which allowed to have dialysate aluminium always below 20 micrograms/l, whereas before it was between 20 and 120 micrograms/l. No significant decrease of their plasma aluminium concentration was observed (81 +/- SEM 12, 81 +/- 12 and 75 +/- 12 micrograms/l respectively). But a significant correlation between plasma aluminium and the total or daily prescribed dose of Al (OH)3 was found before and after 12 months of reverse osmosis. A significant negative correlation was observed between plasma aluminium and the mean corpuscular volume, before and 12 months after reverse osmosis. No correlation was found between plasma aluminium and the plasma PTH levels or with the administration of active vitamin D metabolites. CONCLUSIONS: These data suggest that oral Al (OH)3 plays a predominant role in the hyperaluminemia of hemodialyzed patients and that hyperaluminemia may contribute to their microcytic anemia.

Administration, Oral↗

Water states and water gates in osmotic processes, and the inoperative concept of molfraction of water.

An historical account is given of concepts regarding the mechanism of osmosis and imbibition, starting with Lord Kelvin's gravitational column, where he pointed out that a capillary standing in a dish of water within an isothermal enclosure must have a lowered vapor pressure at its elevated meniscus so as to match that emanating from the surface in the dish, otherwise distillation would violate the Second law. A brilliant sequence to this simple idea followed through Poynting, Arrhenius, Noyes and culminated with Hulett, who in 1901 formulated the "solvent tension theory" of osmosis, stating in essence that the thermal motion of the solute molecules by impact with the free solvent surface put the solvent under tension. This lowers the vapor pressure and thereby also its freezing point. Perrin, in famous experiments on Brownian motion, demonstrated solute-solvent independence within a solution and further support came through Herzfeld, Mysels and Duclaux. We measured negative pressures in salt-free sap of mangroves and other plants matching the osmotic pressure in the leaf cells. A series of measurements on magnetic and gravitational effects on osmotic pressure likewise bore out the tension theory. The fashionable "water concentration theory" is left experimentally contradicted and in violation of the Second law.

Capillary Action↗

Aquaporin-1 in the peritoneal membrane: Implications for water transport across capillaries and peritoneal dialysis.

Peritoneal dialysis (PD) is an established mode of renal replacement therapy, based on the exchange of fluid and solutes between blood in peritoneal capillaries and a dialysate that has been introduced in the peritoneal cavity. The dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. Computer simulations predicted that the membrane contains ultrasmall pores (radius < 3 A) responsible for the transport of solute-free water across the capillary endothelium during crystalloid osmosis. The distribution of the water channel aquaporin-1 (AQP1), as well as its molecular structure ensuring an exquisite selectivity for water perfectly fit with the characteristics of the ultrasmall pore. Treatment with corticosteroids induces the expression of AQP1 in peritoneal capillaries and increases water permeability and ultrafiltration in rats, without affecting the osmotic gradient and the permeability for small solutes. Studies in knockout mice provided further evidence that osmotically-driven water transport across the peritoneal membrane is mediated by AQP1. AQP1 and endothelial NO synthase (eNOS) show a distinct regulation within the endothelium lining peritoneal capillaries. In acute peritonitis, the upregulation of eNOS and increased release of NO dissipate the osmotic gradient and result in ultrafiltration failure, despite the unchanged expression of AQP1. These data illustrate the potential of the peritoneal membrane to investigate the role and regulation of AQP1 in the endothelium. They also emphasize the critical role of AQP1 during peritoneal dialysis and suggest that manipulating AQP1 expression may be used to increase water permeability across the peritoneal membrane.

Animals↗

Release performance of a poorly soluble drug from a novel, Eudragit-based multi-unit erosion matrix.

Mechanisms governing the release of drugs from controlled delivery systems are mainly diffusion, osmosis and erosion. For poorly soluble drugs, the existing mechanisms are limited to osmosis and matrix erosion, that are commonly observed in single unit matrix dosage forms. This study reports formulation and dissolution performance of Eudragit L 100 55 and Eudragit S 100 based multi-unit controlled release system of a poorly soluble thiazole based leukotriene D(4) antagonist, that was obtained by an extrusion/spheronization technique. Effect of triethyl citrate, that was incorporated in the matrix, on the dissolution performance of the drug was also evaluated. In vitro matrix erosion and drug release from the pellets were determined by the use of USP Dissolution Apparatus I, pH 6.8 phosphate buffer, gravimetry and UV spectrophotometry, respectively. Results obtained demonstrated that matrix erosion and drug release occurred simultaneously from the pellets. Pellets eroded with a consequent reduction in size without any change in the pellet geometry for over 12 h. Matrix erosion and drug release followed zero order kinetics. Data obtained strongly suggested a polymer controlled, surface erosion mechanism.

Acrylic Resins↗

Electrolyte management for effective long-term electro-osmotic transport in low-permeability soils.

Electro-osmosis, a coupled-flow phenomenon in which an applied electrical potential gradient drives water flow, may be used to induce water flow through fine-grained sediments. Test cell measurements of electro-osmotic transport in clayey cores extracted from the 27-31 m depth range of the Lawrence Livermore National Laboratory site indicate the importance of pH control within the anode and cathode reservoirs. In our first experiment, pH was not controlled. As a result, carbonate precipitation and metals precipitation occurred near the cathode end of the core, with acidification near the anode. The combination of these acid and base reactions led to the decline of electro-osmotic flow by a factor of 2 in less than one pore volume. In a second experiment, long-term water transport (>21 pore volumes) at stable electro-osmotic conductivity (k(eo) approximately 1 x 10(-9) m2/s-V) was effected with anode reservoir pH > 8, and cathode reservoir pH < 6. Hydraulic conductivity (k(h)) of the same core was 4 x 10(-10) m/s under a 0.07 MPa hydraulic gradient without electro-osmosis. Stable electro-osmotic flow was measured at a velocity of 4 x 10(-7) m/s under a 4 V/cm voltage gradient, and no hydraulic gradient-3 orders of magnitude greater than the hydraulic flow. We also observed chloroform production in the anode reservoir, resulting from electrochemical production of chlorine gas reacting with trace organics. The chloroform was transported electro-osmotically to the cathode, without measurable loss to adsorption, volatilization, or degradation.

Chloroform↗

Transdermal iontophoresis of rotigotine across human stratum corneum in vitro: influence of pH and NaCl concentration.

PURPOSE: The aim of this study was to characterize the influence of pH and NaCl concentration on the transdermal iontophoretic transport of the dopamine receptor agonist rotigotine across human stratum corneum (HSC). METHODS: Rotigotine transport was studied in vitro in side by side diffusion cells according to the following protocol: 6 h of passive diffusion, 9 h of iontophoresis, and 5 h of passive diffusion. A current density of 0.5 mA cm(-2) was used. The influence of donor phase pH (4, 5, and 6) and different concentrations of NaCl (0.07 and 0.14 M) on rotigotine iontophoretic flux were examined. The acceptor phase was phosphate-buffered saline (PBS) at pH 7.4 except in one series of experiments aimed to study the effects of rotigotine solubility on its iontophoretic transport. In this study, PBS at pH 6.2 was used. In separate studies. 14C-mannitol was used as a marker to determine the role of electro-osmosis during iontophoresis. RESULTS: The estimated iontophoretic steady-state flux (Flux(ss)) of rotigotine was influenced by the pH of the donor solution. At a drug donor concentration of 0.5 mg ml(-1), the iontophoretic flux was 30.0 +/- 4.2 nmol cm(-2) h(-1) at pH 6 vs. 22.7 +/- 5.5 nmol cm(-2) h(-1) at pH 5. However, when the donor concentration was increased to 1.4 mg ml(-1), no significant difference in iontophoretic rotigotine transport was observed between pH 5 and 6. Increase of NaCl concentration from 0.07 M to 0.14 M resulted in a decrease of the rotigotine Flux(ss) from 22.7 +/- 5.5 nmol cm(-2) h(-1) to 14.1 +/- 4.9 nmol cm(-2) h(-1). The contribution of electro-osmosis was estimated less than 17%. Probably due to the lipophilic character of the drug, impeding the partitioning of rotigotine from HSC to the acceptor compartment, steady-state transport was not achieved during 9 h of iontophoresis. CONCLUSIONS: Both pH and NaCl concentration of the donor phase are crucial on the iontophoretic transport of rotigotine. Electro-repulsion is the main mechanism of the iontophoretic transport of rotigotine.

Administration, Cutaneous↗

Prevention of biofilm formation in dialysis water treatment systems.

BACKGROUND: Biofilm formations in dialysis systems may be relevant because they continuously release bacterial compounds and are resistant against disinfection. The aim of the study was to compare the development of biofilm between a water treatment system based on a single reverse osmosis unit producing purified dialysate water [bacterial count, 350 colony-forming unit (CFU)/L] (center A) and a water treatment system based on double reverse osmosis and electric deionization, which is continuously disinfected with ultraviolet light and treated with ozone once a week (bacterial count, 1 CFU/L) (center B). METHODS: During a period of 12 weeks, biofilm formation was studied in the tubing segment between the water piping and the dialysis module, using four dialysis monitors in each center. On a weekly basis, tubing samples of 5 cm length (N = 96) were taken under aseptic conditions and investigated for microbiologic contamination [cystine lactose electrolyte-deficient (CLED) Agar], endotoxin levels [limulus amoeben lysate (LAL) gel test, cutoff value, 0.0125 EU/mL], and biofilm formation [electron scanning microscopy (SEM)]. RESULTS: In center A, tube cultures were positive (>100 CFU/mL) in 16% of samples at 22 degrees C and 37 degrees C, compared to 3% of samples of center B (P < 0.05; chi-square). Endotoxin levels were positive in 76% of the tubing samples of center A and negative in all of the samples of center B (P < 0.05). Biofilm was present in 91.7% of the samples of center A (Fig. 1), and only present in one sample (taken after 9 weeks) of center B (P < 0.05) (Fig. 2). In center A, biofilm formation was already observed after 1 week. CONCLUSION: In contrast to a standard water treatment system producing purified water, the use of a system producing highly purified water, which is also treated with regular disinfection procedures, leads to a significant reduction in biofilm formation, bacterial growth, and endotoxin levels in a highly vulnerable part of a water treatment system.

Biofilms↗

Pilot-scale evaluation of select nitrate removal technologies.

Due to the extensive application of artificial nitrogen-based fertilizers and animal manure on land, many water agencies face problems of increasing concentrations of nitrate in groundwater. The contamination of groundwater by nitrate may pose a significant public health problem. The threat of methemoglobinemia is well documented and reflected in the US drinking water standard of 10 mg/L as nitrate-nitrogen. Approximately 45% of Saskatchewan's population use groundwater for drinking purposes, out of which, approximately 23% (230,000) are rural residents. The water used is made available from over 48,000 privately owned wells in regions where there is an extensive application of chemical fertilizers. Biological denitrification, ion exchange, and reverse osmosis (RO) processes were selected for a field study. Field studies were conducted on these processes. The sulfur/limestone autotrophic denitrification (SLAD) process was selected to achieve biological removal of nitrate from groundwater. The feasibility of the system was evaluated under anaerobic conditions. An ion exchange study was conducted using Ionac A554 which is a strong anion exchange resin. In the case of groundwater containing low sulfate concentrations, A554 offered high nitrate removal. However, the disposal of regenerant brine can be a problem. A reverse osmosis unit with Filmtec membrane elements (FT30-Element Family) was used in the study on nitrate removal. The unit effluent average nitrate concentration was less than the maximum allowable concentration.

Bioreactors↗

A physical interpretation of the phenomenological coefficients of membrane permeability.

A "translation" of the phenomenological permeability coefficients into friction and distribution coefficients amenable to physical interpretation is presented. Expressions are obtained for the solute permeability coefficient omega and the reflection coefficient sigma for both non-electrolytic and electrolytic permeants. An analysis of the coefficients is given for loose membranes as well as for dense natural membranes where transport may go through capillaries or by solution in the lipoid parts of the membrane. Water diffusion and filtration and the relation between these and capillary pore radius of the membrane are discussed. For the permeation of ions through the charged membranes equations are developed for the case of zero electrical current in the membrane. The correlation of sigma with omega and L(p) for electrolytes resembles that for non-electrolytes. In this case omega and sigma depend markedly on ion concentration and on the charge density of the membrane. The reflection coefficient may assume negative values indicating anomalous osmosis. An analysis of the phenomena of anomalous osmosis was carried out for the model of Teorell and Meyer and Sievers and the results agree with the experimental data of Loeb and of Grim and Sollner. A set of equations and reference curves are presented for the evaluation of omega and sigma in the transport of polyvalent ions through charged membranes.

Biological Transport↗

Silicon and aluminium interactions in haemodialysis patients.

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

Aluminum↗

Onion root water transport sensitive to water channel and K+ channel inhibitors.

Transroot osmotic water flux (Jos) and radial hydraulic conductivity (Lpr) in onion roots were greatly increased by three means; infiltration of roots by pressurization, repetition of osmosis and chilling at 5 degrees C. Jos was strongly reduced by the water channel inhibitor HgCl2 (91%) and the K+ channel inhibitor nonyltriethylammonium (C9, 75%), which actually made the membrane potential of root cells less sensitive to K+. C9 decreased the rate of turgor reduction induced by sorbitol solution to the same extent as HgCl2. Thus, C9 is assumed to decrease the hydraulic conductivity (Lp) of the plasma membrane by blocking water channels, although possible inhibition of the plasmodesmata of the root symplast by C9 cannot be excluded. Onion roots transported water from the tip to the base in the absence of the osmotic gradient. This non-osmotic water flux (Jnos) was equivalent to Jos induced by 0.029 M sorbitol. Jnos increased when Jos was increased by repetition of osmosis and decreased when Jos was decreased by either HgCl2 or by C9. The correlation between Jnos and Jos suggests that non-osmotic water transport occurs via the same pathways as those for osmotic water transport.

Aquaporins↗

Osmotic flow equations for leaky porous membranes.

A basic set of equations describing the flows of volume (Jv) and solute (Js) across a leaky porous membrane, coupled to the differences of osmotic and hydrostatic pressures d pi and dP has been derived by using general frictional theory. Denoting the mean pore concentration of solute by c*s and the hydraulic and diffusive conductances by Lp and Ps/RT the equations take the form Jv = LpdP + sigma sLp d pi Js = c*s(1 - sigma f)Jv + Ps d pi/RT sigma s = theta (1 - DsVs/DwVw - Ds/Dos) sigma f = 1 - theta DsVs/DwVw - Ds/Dos in which Dw and Ds are the diffusion coefficients for water and solute in the pore and Dos that for free solution. The relation between the reflection coefficients sigma s and sigma f for osmosis and ultrafiltration is then given by sigma s = sigma f - (1- theta)(1 - Ds/Dos), where theta is the diffusive-driven:pressure-driven flow ratio. These equations follow from the fact that in leaky pores osmosis occurs by diffusion alone and that there cannot be any Onsager symmetry leading to sigma s = sigma f. Symmetry holds in the limits where either the pore is small, when sigma s = sigma f = 1, or where the pore is large when sigma s = sigma f = 0.

Biological Transport↗

Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit.

1. In order to study its role in steady state water transport, the Na+-glucose cotransporter (SGLT1) was expressed in Xenopus laevis oocytes; both the human and the rabbit clones were tested. The transport activity was monitored as a clamp current and the flux of water followed optically as the change in oocyte volume. 2. SGLT1 has two modes of water transport. First, it acts as a molecular water pump: for each 2 Na+ and 1 sugar molecule 264 water molecules were cotransported in the human SGLT1 (hSGLT1), 424 for the rabbit SGLT1 (rSGLT1). Second, it acts as a water channel. 3. The cotransport of water was tightly coupled to the sugar-induced clamp current. Instantaneous changes in clamp current induced by changes in clamp voltage were accompanied by instantaneous changes in the rate of water transport. 4. The cotransported solution was predicted to be hypertonic, and an osmotic gradient built up across the oocyte membrane with continued transport; this resulted in an additional osmotic influx of water. After 5-10 min a steady state was achieved in which the total influx was predicted to be isotonic with the intracellular solution. 5. With the given expression levels, the steady state water transport was divided about equally between cotransport, osmosis across the SGLT1 and osmosis across the native oocyte membrane. 6. Coexpression of AQP1 with the SGLT1 increased the water permeability more than 10-fold and steady state isotonic transport was achieved after less than 2 s of sugar activation. One-third of the water was cotransported, and the remainder was osmotically driven through the AQP1. 7. The data suggest that SGLT1 has three roles in isotonic water transport: it cotransports water directly, it supplies a passive pathway for osmotic water transport, and it generates an osmotic driving force that can be employed by other pathways, for example aquaporins.

Animals↗

Water pumps.

The transport of water across epithelia has remained an enigma ever since it was discovered over 100 years ago that water was transported across the isolated small intestine in the absence of osmotic and hydrostatic pressure gradients. While it is accepted that water transport is linked to solute transport, the actual mechanisms are not well understood. Current dogma holds that active ion transport sets up local osmotic gradients in the spaces between epithelial cells, the lateral intercellular spaces, and this in turn drives water transport by local osmosis. In the case of the small intestine, which in humans absorbs about 8 l of water a day, there is no direct evidence for either local osmosis or aquaporin gene expression in enterocytes. Intestinal water absorption is greatly enhanced by glucose, and this is the basis for oral rehydration therapy in patients with secretory diarrhoea. In our studies of the intestinal brush border Na+-glucose cotransporter we have obtained evidence that there is a direct link between the transport of Na+, glucose and water transport, i.e. there is cotransport of water along with Na+ and sugar, that will account for about 50 % of the total water transport across the human intestinal brush border membrane. In this short review we summarize the evidence for water cotransport and propose how this occurs during the enzymatic turnover of the transporter. This is a general property of cotransporters and so we expect that this may have wider implications in the transport of water and other small polar molecules across cell membranes in animals and plants.

Animals↗

Outer hair cell length changes in an external electric field. I. The role of intracellular electro-osmotically generated pressure gradients.

Brownell et al. [Science 227, 194-196 (1985)] observed that an isolated, cylindrically shaped cochlear outer hair cell can change its length when an electric field is applied. In their experiments, the cell was fixed at one end, and located between two electrodes which lie on the cell axis but were positioned far from the cell. Kachar et al. [Nature 322, 365-368 (1986)] had suggested that the cell's electrically evoked elongation could be caused by pressure gradients resulting from electro-osmosis of the intracellular fluid. A mathematical model is developed which predicts the length change that would result from electro-osmotically generated pressure gradients inside the cell. Estimated parameter values are included to demonstrate that the pressures generated by electro-osmosis inside the cell would result in elongations that are at least two orders of magnitude below the experimentally measured values.

Cytoplasm↗

Volume absorption in the pars recta. II. Hydraulic conductivity coefficient.

We evaluated the hydraulic conductivity (Pf, micron s-1) of superficial proximal straight tubules isolated from rabbit kidney. Tubules were perfused with hypotonic (270 mosmol/kg H2O) and bathed with isotonic (290 mosmol/kg H2O) NaCl buffers at 25 degrees C. Due to the tendency of transepithelial osmosis plus solute entry to produce osmotic equilibrium along the perfused length, we observed that the total net volume absorption ('JV, nl min-1) increased from 0.64 to 2.21 when the perfusion rate (VO, nl min-1) was increased from 11 to 45 in a group of tubules with an average length of 0.86 mm. From a 'JV of 2.21 nl min-1 at VO = 45 nl min-1 we computed a minimum Pf of 2,200 micron s-1. And extrapolation of the data to VO leads to infinity gave a Pf value of 5,200-7,600 micron s-1. The same perfusion rate dependence of 'JV in a group of tubules with an average length of 3.29 mm gave quantitatively similar results. A theoretical analysis of radial osmosis occurring simultaneously with axial osmotic equilibration showed that Pf values in the range of 3,000-4,000 micron s-1 accurately predicted the observed relations between VO, 'JV, and tubule length.

Absorption↗

Evolution and design of 'rate controlled' osmotic forms.

A new type of therapeutic system, the precision release osmotic form, has recently been developed. This new dosage form has been referred to in other publications as the gastro-intestinal therapeutic system (GITS). Its action is based on the principles of osmosis as a means of delivering precise amounts of drug over prolonged periods of time. The precision release form has evolved from a prototype design through a simplification and miniaturization process into the elementary osmotic pump, a simple, elegant delivery form that permits controlled drug release by osmosis. Sodium indomethacin trihydrate is the first drug to be incorporated into this precision release form ('Osmosin'). Comparisons with conventional drug forms have shown 'Osmosin' to produce more sustained and constant drug release profiles, thus aiming to improve the therapeutic applicability of a drug through a reduction in dose-related side-effects and allowing once-daily dosing.

Delayed-Action Preparations↗

Hyperosmosis of cerebral injury.

Changes in tissue osmolarity or cerebrospinal fluid osmolarity after cerebral injury have received little attention in the literature, but osmosis may be an important cause of early cerebral edema. This paper reviews concepts and terms relating to osmosis, and reviews the few papers in the literature which have studied osmolarity after cerebral injury. In studies of both traumatic brain injury and ischemia, tissue osmolarity is elevated. Osmolarity of cerebrospinal fluid has also been shown to increase with injury. There have been no human studies examining osmolarity of tissue or cerebrospinal fluid after cerebral injury. Theoretical implications of the osmotic gradient are discussed.

Animals↗