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Short bacterial DNA fragments: detection in dialysate and induction of cytokines.

A number of bacterial cytokine-inducing substances (CIS) such as lipopolysaccharides (LPS) and exotoxins have been detected in dialysate and may contribute to inflammation in hemodialysis patients. Short DNA fragments, oligodeoxynucleotides (ODN) of 6 to 20 nucleotides, are able to bind to Toll-like receptors and are stimulatory on immune cells. ODN induce natural killer cell activity and induce IFN-gamma, TNF-alpha, and IL-6 from mononuclear cells. The presence of ODN in dialysate samples and bacterial cultures was investigated. ODN were extracted from fluids by adsorption to reverse-phase columns. ODN were detected in 18 of 20 investigated dialysate samples, in eight of 10 reverse-osmosis water samples, and in all cultures from various bacterial strains. The presence of bacterial DNA in dialysate was confirmed by PCR specific for bacterial tRNA gene sequences. Saline for intravenous use contained 0.02 +/- 0.01 microg/ml DNA, dialysate samples contained 0.28 +/- 0.02 microg/ml, and Pseudomonas cultures contained 1.0 +/- 0.03 microg/ml DNA. ODN from bacterial cultures were only partially removed by ultrafiltration and were able to diffuse through regular high-flux dialyzer membranes. Synthetic cytosine-guanosine dinucleotide-containing ODN were able to induce IL-6 in human mononuclear cells. It is concluded that short bacterial-derived DNA fragments are present in clinically used fluids, e.g., dialysate. These fragments are of sufficient small size to pass through dialyzer membranes. Bacterial DNA fragments may be an overlooked factor contributing to inflammation in hemodialysis patients.

Cytokines↗

Use of self-expanding, hydrophilic osmotic expanders (hydrogel) in the reconstruction of congenital clinical anophthalmos.

PURPOSE OF REVIEW: Rehabilitation of the congenitally anophthalmic orbit is frustrating to both the parents and physician. Traditional methods involve using progressively enlarging static acrylic conformers to expand the conjunctival socket, followed by placement of conventional static spherical orbital implants, dermis-fat grafts, or inflatable balloon expanders for orbital enlargement. Limitations of these methods typically result in less-than-optimal cosmetic outcomes, with retardation of bony orbital and overlying soft tissue growth adversely affecting midfacial growth and symmetry. Recent advances in tissue expansion technology may offer additional, novel alternatives to conventional therapies. RECENT FINDINGS: Hydrogel tissue expanders were recently adapted for use in congenital anophthalmia. The expanders are placed in their dry, contracted states, and expand gradually to their full size via osmosis of surrounding tissue fluid, with up to a 10-fold increase in volume. Offering the benefit of predictable and controllable self-expansion, hydrogel expanders may offer yet another alternative or adjunctive therapy to the early rehabilitation of the contracted socket. Separate appliances are used for conjunctival and orbital reconstruction. Initial results appear promising. Tempering the enthusiasm for their use, however-particularly in terms of implanted orbital expanders-is the recent spate of long-term complications reported from previous uses of hydrogels as scleral buckling material. SUMMARY: Self-expanding hydrogel tissue expanders appear to offer an intriguing reconstructive alternative to the frustrating condition of congenital anophthalmia. Long-term safety of the material as an orbital implant has not yet been demonstrated, but early results are promising.

Anophthalmos↗

Magnetic resonance imaging findings in substance abuse: alcohol and alcoholism and syndromes associated with alcohol abuse.

Alcohol abuse is common among the population and results in significant diseases that shorten life span. Ethanol may result in chronic brain changes such as atrophy but may also result in neurologic disease that may be acute or chronic and sometimes life threatening. Accompanying vitamin deficiencies may lead to Wernicke's encephalopathy and changes in serum osmosis may lead to several acute demyelinating disorders. In addition, pregnant women who consume alcohol place their babies at high risk for the fetal alcohol syndrome. In this article we review these disorders and emphasize their imaging features.

Alcohol-Induced Disorders, Nervous System↗

Characterizing uncommon Burkholderia cepacia complex isolates from an outbreak in a haemodialysis unit.

An outbreak of bacteraemia in a haemodialysis unit where 65 episodes of infection involved 35 outpatients is reported. Burkholderia cepacia complex was the agent most frequently recovered from blood. Thirty-three environmental and clinical isolates of B. cepacia complex were characterized by whole-cell protein electrophoresis and recA-RFLP profile. Fourteen isolates were genomovar I and 16 isolates were not classifiable by their recA-RFLP pattern. Ribotyping, random amplification of polymorphic DNA (RAPD) and integron profile were used to explore the clonality of the isolates, and revealed multiple strain genotypes. Four ribotypes and RAPD types and three integron patterns were identified. The water supply was identified as the source of the outbreak, and inappropriate cleaning and a leak in the reverse osmosis tubing connection were the probable causes of contamination. B. cepacia complex was still recovered from blood of patients even after apparently adequate measures were taken and water quality standards were met, suggesting that higher standards for water quality should be adopted in haemodialysis units. The genomovars recovered here were distinct from those commonly reported for cystic fibrosis isolates.

Burkholderia Infections↗

Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. II. A linear double-layer analysis

Frequency-dependent fluid flow in electrolytes on microelectrodes subjected to ac voltages has recently been reported. The fluid flow is predominant at frequencies of the order of the relaxation frequency of the electrode-electrolyte system. The mechanism responsible for this motion has been termed ac electro-osmosis: a continuous flow driven by the interaction of the oscillating electric field and the charge at the diffuse double layer on the electrodes. This paper develops the basis of a theoretical approach to this problem using a linear double layer analysis. The theoretical results are compared with the experiments, and a good correlation is found.

Journal Article↗

Electro-osmotically induced convection at a permselective membrane

The paper is concerned with convection at an ion exchange electrodialysis membrane induced by nonequilibrium electro-osmosis in the course of concentration polarization under the passage of electric current through the membrane. Derivation of nonequilibrium electro-osmotic slip condition is recapitulated along with the linear stability analysis of quiescent electrodiffusion through a flat ion exchange membrane. Results of numerical calculation for nonlinear steady state convection, developing from the respective instability, are reported along with those for a slightly wavy membrane. Besides these results, we report those of time dependent calculations for periodic and chaotic oscillations, resulting from instability of the respective steady state flows, and also the results of recent experiments with modified membranes. These latter rule in favor of electro-osmotic versus bulk electroconvective origin of overlimiting conductance through ion exchange membranes.

Journal Article↗

Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. III. Observation of streamlines and numerical simulation.

The application of a nonuniform ac electric field to an electrolyte using coplanar microelectrodes results in steady fluid flow. The flow has its origin in the interaction of the tangential component of the nonuniform field with the induced charge in the electrical double layer on the electrode surfaces. Termed ac electro-osmosis, the flow has been studied experimentally and theoretically using linear analysis. This paper presents experimental observations of the fluid flow profile obtained by superimposing images of particle movement in a plane normal to the electrode surface. These experimental streamlines demonstrate that the fluid flow is driven at the surface of the electrodes. Experimental measurements of the impedance of the electrical double layer on the electrodes are also presented. The potential drop across the double layer at the surface of the electrodes is calculated numerically using a linear double layer model, and also using the impedance of the double layer obtained from experimental data. The ac electro-osmotic flow at the surface of the electrodes is then calculated using the Helmholtz-Smoluchowski formula. The bulk fluid flow driven by this surface velocity is numerically calculated as a function of frequency and good agreement is found between the numerical and experimental streamlines.

Journal Article↗

Thin double layer approximation to describe streaming current fields in complex geometries: analytical framework and applications to microfluidics.

We set up an analytical framework that allows one to describe and compute streaming effects and electro-osmosis on an equal footing. This framework relies on the thin double layer approximation commonly used for description of electroosmotic flows, but rarely used for streaming problems. Using this framework we quantitatively assess the induction of bulk streaming current patterns by topographic or charge heterogeneities on surfaces. This too also permits analytical computation of all linear electrokinetic effects in complex microfluidic geometries, and we discuss a few immediate applications.

Journal Article↗

Negative pressures produced in an artificial osmotic cell by extracellular freezing.

A rigid artificial osmotic cell has been constructed using reverse osmosis membranes that were supported by metal grids from both sides to yield a high elastic modulus of the system. The cell could be subjected to changes of external water potential either by evaporation or by application of hypertonic solutions so that negative internal pressures or tensions (i.e. pressures smaller than atmospheric) could be built up. Negative pressures were also obtained by freeze-induced dehydration when the cell was cooled to -1.5 degrees C and ice was formed on the outer surface. Tensions of up to -0.7 megapascals (-7 bars) could be established in the different types of experiments. Smaller tensions could be kept in the cell for several hours. Cavitations caused the pressure to increase instantaneously to values of about -0.1 megapascals (relative to atmospheric pressure) as theoretically expected. Cavitations could be reversed by pressurizing the system. The cell could be cooled to subzero temperatures while the cell solution was under tension. Intracellular freezing could be easily detected from an instantaneous increase in pressure. When the membrane was not supported by a grid from the inside (analogous to the situation in plant cells), no tensions could be built up in the system. The results support the idea of the incidence of negative pressures during freezing, if the wall is sufficiently rigid to prevent cell collapse and if the membrane does not separate from the cell wall.

Journal Article↗

Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine-induced itch and flare response in human skin in vivo.

BACKGROUND: In a previous study, iontophoresis of nedocromil sodium into human skin in vivo was shown to reduce histamine-induced itch and flare. In asthma, the Na+/K+/2Cl- cotransporter inhibitors, frusemide and bumetanide, have been reported to have many similar actions to nedocromil sodium. OBJECTIVE: To compare the effects of these drugs in the histamine-induced itch, flare and weal response in human skin in vivo and elucidate their site of action. METHODS: Nedocromil sodium, frusemide bumetanide and reversed osmosis water (control), were introduced by iontophoresis into the forearm skin of 10 volunteers in each of two single-blind studies. In study 1, histamine (20 microL of 100 microM) or vehicle was injected into the area of iontophoresis 10 min later. In study 2, histamine or vehicle was injected 5 mm outside the area of iontophoresis so the flare developed over the area of iontophoresis. Itch was scored on a visual analogue scale every 20 s for 5 min, flare areas were assessed using scanning laser Doppler imaging up to 10 min and weal was assessed by planimetry at 10 min. RESULTS: In study 1, nedocromil sodium, frusemide and bumetanide reduced itch scores by 36%, 48% and 34%, respectively, and flare areas by 17%, 26% and 15% respectively (all P<0.05). Weal areas and blood flux in the flare were unaffected. In study 2, itch scores, flare areas and weal areas were not inhibited. Also, blood flux values in areas of drug and water iontophoresis were not different. CONCLUSION: This study has provided evidence to support the hypothesis that nedocromil sodium, frusemide and bumetanide inhibit sensory nerve activation to reduce the itch and flare responses induced by histamine in human skin in vivo. It is likely that inhibition of a Na+/K+/2Cl- cotransporter in the sensory nerve membrane is a possible mechanism of action.

Adult↗

Assessment of an Australian medical internship.

The work patterns of interns were observed, recorded and analysed into categories descriptive of service and training functions. As would be expected, the service component predominated, while only 7-13% of interns' time could be identified as educative. Interns make little use of formal postgraduate educational sessions and visit the library rarely. They acquire the necessary clinical skills and attitudes to fit them for future practice largely by osmosis and from discussions with residents and registrars. Consultants play only a small role in their education . Non-formal education, which is acquired as part of the service function, has the most potential for effective training. Its unsystematic character, however, may present a problem for both interns and their supervisors since neither may have a comprehensive view of what requires to be learned or what progress is being made. There is a need for interns and their supervisors to identify the learning objectives and experiences which they should attain during each term.

Australia↗

Oxidative gating of water channels (aquaporins) in corn roots.

An oxidative gating of water channels (aquaporins: AQPs) was observed in roots of corn seedlings as already found for the green alga Chara corallina. In the presence of 35 mM hydrogen peroxide (H2O2)--a precursor of hydroxyl radicals (*OH)--half times of water flow (as measured with the aid of pressure probes) increased at the level of both entire roots and individual cortical cells by factors of three and nine, respectively. This indicated decreases in the hydrostatic hydraulic conductivity of roots (Lp(hr)) and of cells (Lp(h)) by the same factors. Unlike other stresses, the plant hormone abscisic acid (ABA) had no ameliorative effect either on root LP(hr) or on cell Lp(h) when AQPs were inhibited by oxidative stress. Closure of AQPs reduced the permeability of acetone by factors of two in roots and 1.5 in cells. This indicated that AQPs were not ideally selective for water but allowed the passage of the organic solute acetone. In the presence of H2O2, channel closure caused anomalous (negative) osmosis at both the root and the cell level. This was interpreted by the fact that in the case of the rapidly permeating solute acetone, channel closure caused the solute to move faster than the water and the reflection coefficient (sigma s) reversed its sign. When H2O2 was removed from the medium, the effects were reversible, again at both the root and the cell level. The results provide evidence of oxidative gating of AQPs, which leads on to inhibition of water uptake by the roots. Possible mechanisms of the oxidative gating of AQPs induced by H2O2 (*OH) are discussed.

Abscisic Acid↗

Corneal endothelial changes in superficial epithelial keratopathy.

A series of five cases is described in which superficial punctate keratopathy was associated with endothelial cell changes. The most striking change was the presence of dark areas or blebs, usually two to four cell diameters in extent. There was also distortion and crumpling of the corneal endothelium, mild pleomorphism and polymegathism of the endothelial cells, with a reduced cell count in some cases. These blebs have previously been reported in hard and soft contact lens wearers and are due to intercellular oedema with separation of endothelial cells from Descemet's membrane. Anoxia and interference with osmosis have been proposed as possible mechanisms for the production of these blebs, but our cases demonstrate that fine disruption of the corneal epithelium can affect the integrity of the corneal endothelium and may lead to significant damage over a long period of time.

Adult↗

Infusion-free hemodiafiltration: simultaneous hemofiltration and dialysis with no need for infusion fluid.

A new simultaneous hemofiltration and dialysis system was developed which has no need of infusion fluid. The system employs two hemodiafilters in a direct series. An ultrafiltration rate and dialysate flow rate control system was employed to control the dialysate flow at the inlet and outlet, and the difference in volume was arranged to be the amount of water removed from the body. When the blood circuit was narrowed between the two hemodiafilters, the ultrafiltration was performed at the first hemodiafilter; at the second one, the dialysate moved to the blood side as a dilution fluid. To remove pyrogens and bacteria, tap water was subjected to activated charcoal, ion exchange and reverse osmosis treatment, followed by preparation of the dialysate. In clinical evaluation, this system showed marked improvement in clearance of middle and large molecules.

Adult↗

The efficacy and safety of the new heparin-induced extracorporeal low-density lipoprotein precipitation system (Plasmat Futura) in comparison with the currently used system (Plasmat Secura).

The aim of the present study was to examine whether the recently introduced heparin-mediated extra-corporeal low-density lipoprotein precipitation (HELP) apheresis system Plasmat Futura (since 2001) was comparable to Plasmat Secura system, used to date, in its efficiency to remove atherogenic components, its ease of handling and operating as well as clinical safety and patient compliance. Coronary heart disease (CHD) patients (N = 21) were first treated with Plasmat Secura system and 13 of them were then randomly switched over to the upgraded Plasmat Futura system. Eight patients remained on Secura system. All together, 40 Futura treatments and 40 Secura treatments were performed. Blood samples were collected immediately before and after each apheresis therapy. Our data showed no significant differences in the reduction of plasma low-density lipoprotein, lipoprotein (a) and fibrinogen by Plasmat Futura and Secura system (P > 0.05). However, the major advantages of Plasmat Futura system are the ready-to-use sterile dialysis solutions instead of reverse osmosis device in Plasmat Secura, which ensures flexibility and lower risk of cross infections. Long-term tolerance and safety parameters showed no significant difference (P > 0.05). On the basis of our studies. Plasmat Futura system is easy to use, shows no adverse events and is comparable to Plasmat Secura in its capacity to remove proatherogenic plasma factors.

Blood Component Removal↗

The water crisis in the gaza strip: prospects for resolution.

Israel and the Palestinian Authority share the southern Mediterranean coastal aquifer. Long-term overexploitation in the Gaza Strip has resulted in a decreasing water table, accompanied by the degradation of its water quality. Due to high levels of salinity and nitrate and boron pollution, most of the ground water is inadequate for both domestic and agricultural consumption. The rapid rate of population growth in the Gaza Strip and dependence upon ground water as a single water source present a serious challenge for future political stability and economic development. Here, we integrate the results of geochemical studies and numerical modeling to postulate different management scenarios for joint management between Israel and the Palestinian Authority. The chemical and isotopic data show that most of the salinity phenomena in the Gaza Strip are derived from the natural flow of saline ground water from Israel toward the Gaza Strip. As a result, the southern coastal aquifer does not resemble a classic "upstream-downstream" dispute because Israel's pumping of the saline ground water reduces the salinization rates of ground water in the Gaza Strip. Simulation of different pumping scenarios using a monolayer, hydrodynamic, two-dimensional model (MARTHE) confirms the hypothesis that increasing pumping along the Gaza Strip border combined with a moderate reduction of pumping within the Gaza Strip would improve ground water quality within the Gaza Strip. We find that pumping the saline ground water for a source of reverse-osmosis desalination and then supplying the desalinated water to the Gaza Strip should be an essential component of a future joint management strategy between Israel and the Palestinian Authority.

Conservation of Natural Resources↗

Transcapillary fluid movements in sympathectomized intestine and skin during hemorrhagic hypotension.

Net transcapilary fluid exchange in skin tissue (paw) and small intestine was observed during a 90 min period of hemorrhagic hypotension at 50 mm Hg in the cat. Reflex fluid transfer was prevented by regional sympathectomy and chi-adrenergic blockade. Early in hemorrhage, fluid absorption from the extravascular space occurred in both tissues, apparently caused by osmosis. The process was thus co-ordinated in time with a positive arterio-venous osmolar difference, in turn caused by a marked arterial hypersomolality. Experimetnal arterial hyperosomolality of similar magnitude, created by i.v. infusion of hypertonic glucose in non-bled animals, led to transcapillary fluid absorption in both intestine and skin and at rates similar to those in bleeding. Regional hypotsionen per se caused no fluid absorption. Later in hemorrhage (greater than 30 min), plasma fluid moved into the extravascular space both in skin and intestine, apparently due to a gradual increase of cappilary hydrostatic pressure. It is concluded that the arterial hypersomolality during bleeding can cause transcapillary fluid absorption in intestinal and skin tissues, as previously shown for skeletal muscle (Järhult 1973). The hemodynamic significance of this process for plasma volume regulation in hemorrhage is, however, much greater in skeletal muscle than in intestine and skin, mainly due to the much larger total mass of the muscle tissue.

Adrenergic alpha-Antagonists↗

Correlation between chloride flux via the mitochondria-rich cells and transepithelial water movement in isolated frog skin (Rana esculenta).

The coupling between net transepithelial Cl- influx and net water flow was investigated. Experiments were performed on isolated frog skin bathed in isotonic Cl- Ringer's solution in the presence of the Na+ channel blocking agent amiloride in the mucosal solution. The skins were voltage-clamped at -80 or -100 mV (with the serosal solution as reference). Under these conditions the current across the skin is carried by an influx of Cl-. In the absence of antidiuretic hormone the correlation between current and net water flow was low, but in the presence of the antidiuretic hormone, arginine vasotocin, there was a highly significant correlation between current and net water flow. The data presented here indicate that under steady state conditions about 70 molecules of water follow each Cl- ion across the skin. If the water influx is driven by electroosmosis one would expect that a change in current should result in an immediate change in the water flow. There was, however, a considerable time delay between the change in current and water flow. This indicates that the observed coupling between Cl- flux and water flow is caused by current-induced local osmosis and not electroosmosis.

Amiloride↗