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Analysis of skin permeation-enhancing mechanism of iontophoresis using hydrodynamic pore theory.

The effects of constant DC iontophoresis (0-1.5 mA/0.966 cm(2)) on the permeation of three hydrophilic compounds, antipyrine (ANP, M.W. 188.23), sucrose (SR, M.W. 342.30) and 1-kestose (KT, M.W. 506.73), through excised hairless rat skin were evaluated using hydrodynamic pore theory. The electro-osmotic flow caused by iontophoresis was measured using deuterium oxide (D(2)O). The penetration-enhancing mechanism of iontophoresis was found to increase solvent flow through electro-osmosis and pore enlargement and/or new pore production in the skin barrier, together with enhancement of electrochemical potential difference across the skin. These effects were closely related to the strength of the current applied. The electro-osmotic flow of D(2)O (J(D(2)O)) greatly enhanced the skin permeation clearance of all hydrophilic penetrants (CL(drug)). Pore production was classified into reversible and irreversible processes, which resulted from lower (0-0.5 mA/0.966 cm(2)) and higher (0.5-1. 5 mA/0.966 cm(2)) currents, respectively. Thus, the enhancing effects of iontophoresis on skin permeation of nonionic hydrophilic compounds can be explained by increase in pore size and higher solvent flow.

Administration, Topical↗

A history of psychiatric ethics.

In the not-far-distant past, ethics for all doctors was, at best, an ill-attended lecture or two on how to keep out of trouble; it was assumed the rest was absorbed by a form of social and professional osmosis. Although ethics has entered the undergraduate curriculum, continuing medical education programs, journals, and books, it still is in a state of flux. Although immense progress has been made in the last 30 to 40 years, much remains to be done. Trainees are often naïve, and the older generation is on a steep learning curve. An encouraging feature is the current lively debate on matters ethical and how they can best be incorporated into everyday clinical practice. The long-held notion of ethics resting complacently in the paternal arms of Hippocrates has, with almost brutal haste, been projected into a rapidly evolving modern world of technologic, moral, and societal change. Yet, at its core, ethics has to retain its humanism and guard against influences from every quarter that tries to make it a set of rules, thereby negating the diversity and uniqueness of our patients. Even as you read, there will be new influences and pressures on clinical practice that have an ethical dimension. For instance, we are adjusting to new privacy laws in Australia that allow patients, whether public or private, access to their psychiatric records. Globalization is not restricted to world trade; it also operates in the framework of societal change and the wider dissemination and implementation of libertarian views. If such "freedoms" are not currently available to patients, they soon will be. This brief historical foray in identifying some of these forces can assist in their early recognition so that as a profession, we are forewarned and forearmed and, in that respect, be ahead of both Henry Ford ("History is more or less bunk...") [42] and the Bourbons ("They learn nothing and they forget nothing") [43].

Ethics, Medical↗

Microbial contamination of dialysate and its prevention in haemodialysis units.

At the haemodialysis centres of nine hospitals in Japan, microbial contamination of treated water (reverse osmosis method), acid and bicarbonate concentrates, and dialysate was investigated. Among these fluids used in haemodialysis, the dialysate was most frequently contaminated and had the highest concentration of bacteria. Of 40 dialysate samples analysed, 42.5% showed a bacterial count of more than 2000cfu/mL, which was above the Association for the Advancement of Medical Instrumentation (AAMI) standard. However, among the 40 samples from 20 dialysis machines, all six dialysate samples from three dialysis machines that used an ultrafiltration membrane in the circuit before the entrance of the dialysate into the dialyser, showed a bacterial count of < or =10 cfu/mL. In addition, when an ultrafiltration membrane was used in the circuit before the entrance of the dialysate into the dialyser for four dialysis machines showing dialysate samples contaminated with 10(4)-10(5)cfu/mL the bacterial count in dialysate samples from these machines became zero. Because dialysis machines are susceptible to microbial contamination, it is necessary to take measures such as placing an ultrafiltration membrane into the circuit before the entrance of dialysate into the dialyser.

Colony Count, Microbial↗

Microbial contamination of 'sterile water' used in Japanese hospitals.

We examined the following samples of water from 10 hospitals for microbial contamination: water obtained using an ultra filtration system (UF water), a reverse osmosis system (RO water), a water distillation system (distilled water) and tap water. UF water and RO water are used for handwashing before surgery, and distilled water for the preparation of drugs. All 10 samples of tap water examined were contaminated with < 10 colony forming units (cfu)/mL. Thirteen (68%) of 19 samples of UF water, nine (53%) of 17 samples of RO water and 15 (79%) of 19 samples of distilled water were contaminated with 10(1)-10(4) cfu/mL. The majority of micro-organisms were non-fermentative bacteria such as Sphingomonas paucimobilis and CDC gr. IV C-2. Japanese hospitals commonly use UF water and RO water for preoperative handwashing under the assumption that it is sterile. Our results suggest, however, that these types of water are inferior microbiologically to tap water. Distilled water from the dispensary was also contaminated with micro-organisms. The available chlorine content of tap water was 0.17-0.42 ppm and that of UF water (from tap water) 0-0.06 ppm. There was no available chlorine in RO water or distilled water (each from tap water). The reduction or disappearance of available chlorine appears to be associated with microbial contamination of UF water, RO water and distilled water.

Chlorine↗

New methods of nitrate removal from water.

Nitrate contamination in groundwater resources originates mainly from the excessive use of fertilisers and uncontrolled land discharges of treated wastewater. This can cause potential health hazards to infants and pregnant women, thus limiting the direct use of the groundwater resources for the human consumption in several parts of the world, including India. The conventional processes used to eliminate nitrate from water are ion exchange, reverse osmosis and electro-dialysis. The utility of these processes has been limited due to their expensive operation and subsequent disposal problem of the generated nitrate waste brine. This paper presents a comprehensive account of the methods/techniques used for the removal of nitrate ion from water during the last 10 years with special reference to the biological denitrification and fate of the metals in decontamination processes.

Fresh Water↗

High fluoride exposure in hemodialysis patients.

The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride.

Dialysis Solutions↗

The use of ion exchange to remove aluminum from water used in hemodialysis.

Since the established techniques for removing aluminum from the water used in dialysis (reverse osmosis and deionization) are relatively complex and expensive, it was decided to investigate a number of simple ion-exchange techniques. In 48 of 217 tap water samples obtained from 61 home hemodialysis patients in southeast Scotland, the aluminum content exceeded 2 mumol/L (54 micrograms/L)--a level that has been associated with dialysis dementia and fracturing osteodystrophy. Dialysate prepared from this water after softening had approximately half this aluminum content, but in 17 instances the concentration still exceeded 2 mumol/L. In vitro studies showed that the anion-exchange resin IRA 400 (Rohm-Haas, Philadelphia) in the chloride phase was very effective at removing aluminum. A commercial water softener was modified by the addition of this resin, and installed in the home dialysis training unit at the Princess Alexandra Hospital in Brisbane. Over a 12-month period in which the tap water aluminum content averaged over 10 mumol/L (270 micrograms/L), the product water had an aluminum content consistently under 2 mumol/L, being under 1 mumol/L (27 micrograms/L) on 19 out of 20 occasions. The modified softener was regenerated with a saturated sodium chloride solution at 2-week intervals, using the manufacturer's protocol for the unmodified softener. Provided that dialysate and plasma aluminum levels are monitored on a regular basis, it is felt that this simple technique of aluminum removal may be appropriate for many home hemodialysis situations.

Aluminum↗

Cortical v trabecular bone aluminum in dialyzed patients.

Differences among measurement of cortical and trabecular bone aluminum (AI) have been observed. Furthermore, its relationship to bone histology has been variable. In order to clarify these points, we have evaluated measurements of bone AI in relation to the source of AI and bone lesion in 25 hemodialysis patients. All patients were dialyzed in the same unit since commencement of dialysis and treated by the same physician. Age of the patients ranged from 29 to 66 years; mean duration of dialysis was 6.6 +/- 3.5 years. Dialysate water has been treated by reverse osmosis since 1980. Bone biopsy was performed in all patients after double tetracycline labeling. AI was measured biochemically in cortical bone (bCAI) and histochemically in trabecular (TAI) and cortical bone (CAI). Mean serum AI (36 +/- 21 micrograms/L) and bCAI (59 +/- 44 micrograms/g) were increased. There were significant correlations between: cortical AI and (1) serum AI (r = 0.71, p less than 0.001); (2) duration of dialysis with softened water (AI content, 55 +/- 21 micrograms/L, r = 0.65, P less than 0.001) but not with total duration of dialysis; and (3) AI ingested since commencement of dialysis (r = 0.57, P less than 0.01). Trabecular AI was not correlated with any of these parameters. None of cortical AI measurements were correlated with bone formation rates (BFR), osteoblastic surfaces (ObS), and resorption surfaces (RS) determined on trabecular bone. However, trabecular AI was inversely correlated with BFR (P less than 0.01) and ObS (P less than 0.05). Serum parathyroid hormone (PTH) was positively correlated with BFR (P less than 0.001) and RS (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Correction of microcytosis following elimination of an occult source of aluminum contamination of dialysate.

A higher prevalence of aluminum-associated microcytic anemia was noted in hemodialysis unit A (n = 67) compared to unit B (n = 39). This finding could not be explained by differences in the aluminum content of reverse osmosis (RO) water or intake of antacids containing aluminum by patients in the two units. An intermittent source of aluminum contamination was suspected when water aluminum and total dissolved solutes (TDS) were measured at several sites in the water treatment facility of unit A. A one-way valve that maintained unidirectional flow in an RO bypass circuit was found missing. Intermittent pressure changes in this circuit altered the direction of water flow causing mixing of partially purified water with RO water. Installation of the valve stopped contamination and resulted in a decrease in plasma aluminum concentration from 183 +/- 12 micrograms/L to 76 +/- 7.3 micrograms/L, erythrocyte aluminum concentration from 210 +/- 31 micrograms/L to 61 +/- 9 micrograms/L and microcytosis from 58% to 8% in patients (n = 48) when measured 6 months later. Because contamination was missed in spite of water testing at the RO site, these findings underscore the importance of measuring water aluminum and TDS content at the dialysis stations. Frequent water testing at dialysis stations, familiarity with the design of water treatment facilities, and recognition of aluminum overload can lead to early detection and correction if similar types of aluminum contamination should occur.

Aluminum↗

Plasma aluminum levels (unstimulated and stimulated): clinical and biochemical findings in 185 patients undergoing chronic hemodialysis for 4 to 95 months.

Plasma aluminum levels (unstimulated and stimulated by deferoxamine infusion), along with signs and symptoms associated with aluminum overload, were evaluated in 185 patients (97 men, 88 women; mean age, 58 +/- 8 years) who had been undergoing dialysis for 4 to 95 months and who were still receiving treatment in 1985 at a free-standing dialysis facility which has always used water purified by reverse osmosis. Monthly water aluminum levels never exceeded 15 micrograms/L; therefore, the major source of aluminum in these patients was oral phosphate binders. Unstimulated plasma aluminum levels ranged from 7 to 392 micrograms/L, averaged 81.5 +/- 56.4, and did not correlate with the duration of dialysis (r = 0.07; P greater than 0.31) or frequency of symptoms. Stimulated plasma aluminum levels increased in a linear fashion (r = 0.57; P less than 0.0001) with time on dialysis; however, there was no statistical association between the stimulated aluminum levels and a variety of nonspecific musculoskeletal or CNS symptoms, evidence of hyperparathyroidism, hematocrit, or calcium or phosphorus levels. These findings suggest that total body aluminum, as reflected in deferoxamine-stimulated serum aluminum levels, increases as a function of time undergoing dialysis.

Aluminum↗

Membrane-based hybrid processes for high water recovery and selective inorganic pollutant separation.

The removal of heavy metals (e.g. Pb(II), Cd(II), Cu(II), etc.) and oxyanions (e.g. nitrate, As(III, V), Cr(VI), etc.) is of immense interest for treatment of groundwater and other dilute aqueous systems. However, the presence of non-toxic components, such as hardness (Ca, Mg) and sulfate, can interfere with the separation of toxic species. For example, pressure-driven membrane processes, such as reverse osmosis (RO), have been limited for water treatment due to problems that these extraneous components cause with water recovery and ionic strength (osmotic pressure) of the retentate. In addition, nitrate rejection by RO is considerably lower than NaCl rejection, resulting in permeate concentrations that may be too high for groundwater recharging. Other separation systems that rely solely on sorption of toxic species (e.g. ion exchange resins) may not have sufficient selectivity for efficient use in the presence of competing ions. Hence, implementation of pressure-driven membrane separations and high capacity sorbents in hybrid processes shows much promise for remedying these difficulties. For example, selective separation of nitrate may be achieved by combining nanofiltration (NF) for sulfate removal, followed by RO or ion exchange for nitrate removal (see example 1). When small concentrations of toxic metals are present, the large retentate volumes of RO processes may be reduced by selective removal of toxic species with a high capacity sorbent, thus permitting disposal of a lower volume, non-toxic stream (see example 2). The use of microfiltration membrane-based sorbents containing multiple polymeric functional groups is a novel technique to achieve high metal sorption capacity under convective flow conditions. These sorbents are formed by the attachment of various polyamino acids (MW: 2500-10,000), such as polyaspartic acid (cation sorption), polyarginine (oxyanion sorption), and polycysteine (chelation exchange), directly on the membrane pore surfaces. Since these sorbents have also been found to have high selectivity over non-toxic metals, such as calcium, they are ideal candidates for hybrid processing with RO/NF.

Adsorption↗

Selective removal of plutonium 238 from a canal sediment using a carbonate-chelant soil washing technology (ACT*DE*CON).

The Mound laboratory site in Miamisburg, OH, a former plutonium processing facility, contains approximately 40000 yd(3) (30,580 m3) of plutonium- and thorium-contaminated soils and sediments at levels that require remediation. Existing applicable remediation technologies are unsatisfactory, because they are expensive and do not provide volume reduction. ACT*DE*CON is a chemical soil leaching technology for the treatment of soils that utilizes contaminant dissolution via dilute selective solutions to remove radionuclides. In bench-scale tests, process parameters were developed for the optimal treatment of the Miami Erie Canal soil at the Mound site, combining the maximum plutonium removal with an acceptable amount of soil dissolution and minimizing the costs of reagents. Parameters evaluated included soil to extractant mass ratio, temperature, rinse solution composition, kinetics, and the application of several dewatering aids. Plutonium removal rates of >95% were achieved, and the residual plutonium in the treated soil proved to be very immobile-confirming that the process had removed the most accessible species of the radionuclide. Currently being tested at Mound is an engineering scale-up that includes an attrition scrubber, a counter-current extractor, and a reverse osmosis system. Economic evaluations based on bench-scale results put the treatment cost at US$278/yd(3) (US$364/m3), compared to US$350/yd(3) (US$458/m3) for the 'box-and-bury' baseline alternative treatment system.

Carbonates↗

[Plasma osmolarity and cerebral volume].

Under normal physiological conditions, the osmolarity of extracellular fluids (ECFs) and natremia are controlled by two regulatory mechanisms modulating the water balance and sodium outflow from information collected by the osmoreceptors and baroreceptors, respectively. As well, under normal physiological conditions, water and electrolytes of brain ECFs are secreted by the endothelial cells of brain capillaries. Furthermore, isotonicity is present on both sides of the blood-brain barrier. In the event of systemic osmolarity disorders, water transport subject to osmosis laws occurs at the level of the blood-brain barrier. In the case of plasmatic hyperosmolarity cerebral dehydration is observed, while cerebral edema occurs in the contrary case. However, plasmatic osmolarity disorders have less effect on the cerebral volume when their introduction is slow. Experimentation in acute conditions shows that measured variations of the cerebral water content are lower than calculated variations, thus suggesting the existence of an adaptive mechanism, that is, the cerebral osmoregulation which limits the variation of the volume of brain cells by modulating their osmoactive molecule content. These osmoactive molecules are, on the one hand, the electrolytes, which are early and rapidly mobilized, and, on the other hand, the organic osmoles (amino acids, etc.), whose secretion is slower and delayed. This phenomenon should be taken into account in the treatment of osmolarity disorders. Thus, the related-risk of treatment for natremia disorders is therapeutic reversal of the osmotic gradient at the level of the blood-brain barrier. This reversal, which corresponds to a second osmotic stress, requires the implementation of a new procedure of cerebral osmoregulation in the opposite direction of the preceding one. As successive osmotic stresses decrease the effectiveness of brain osmoregulation, the risk for cerebral dehydration and pontine myelinolysis increases when the treatment of chronic hyponatremia is too aggressive. Finally, the choices for infusion solutions in neurosurgery and treatment for osmolarity disorders are also based on the relationships that exist between plasmatic osmolarity and the brain.

Animals↗

Potential for detection of microorganisms and heavy metals in potable water using electronic nose technology.

Studies have been carried out to determine the potential for the detection of different microbial species (Enterobacter aerogenes, Escherichia coli, Pseudomonas aeruginosa), alone and in the presence of low concentrations of different heavy metals (As, Cd, Pb and Zn) in bottled, reverse osmosis (RO) and tap water, using an electronic nose. Studies show that it is possible to discriminate control water samples from water contaminated with 0.5 ppm of a mixture of metals. The presence of heavy metals may modify the activity of microorganisms and thus the volatile production patterns. Bacterial species at 10(2)-10(4) colony forming units (CFUs) ml(-1) could be detected after 24 h of incubation. Work is in progress to identify the limits of detection for a range of other microorganisms, including, fungi and cyanobacteria, and chlorinated phenols using electronic nose technology.

Biomimetics↗

Replaceable polymers in DNA sequencing by capillary electrophoresis.

Much progress has been made in the development of replaceable sieving polymers and capillary coatings for high-performance DNA sequencing by capillary electrophoresis. Several studies of parameters that affect resolution, read length and reproducibility have begun to reveal the physical mechanisms acting on single-stranded DNA during electrophoresis through semidilute polymer solutions. Recently developed electro-osmosis-inhibiting matrix polymers have simplified the process of coating capillaries, facilitating the automation of high-throughput parallel systems for large-scale sequencing.

Biotechnology↗

Physicochemical considerations in the iontophoretic delivery of a small peptide: in vitro studies using arginine vasopressin as a model peptide.

Transdermal iontophoresis (TI) is a physical enhancement technique to facilitate the delivery of primarily charged molecules across the skin. TI of peptides is influenced by a complex interplay of several factors and one of the main issues in optimizing iontophoretic delivery of peptides is to improve the transport efficiency. From this perspective, this study investigates the effect of the physicochemical parameters on the TI of a peptide arginine vasopressin (AVP). The permeation of AVP showed a linear dependence on the concentration of drug in the donor medium. The iontophoretic flux of AVP was strongly influenced by the pH of the donor solution. Increasing the pH from 5.16 to 7.4 resulted in a decrease in the enhancement ratio by 4.5 times. When the ionic strength was increased by varying the amount of NaCl from 0.05 to 0.25 M the flux was found to decrease by 3.2 times. Replacing normal saline in the receptor compartment by HEPES buffer showed a resultant four times increase in drug permeation. The physiochemical parameters of the donor medium play a significant role in the efficiency of drug delivery by iontophoresis for a small peptide like AVP. Though electrorepulsion would be expected to be the main mechanism involved in the movement of charged molecules across the skin by iontophoresis, for peptides in the molecular weight range of AVP, other associated secondary effects like osmosis, electroosmosis and counter ion flow may also play a significant role in transport across the skin.

Administration, Cutaneous↗

Chloramine removal from water used in hemodialysis.

Several outbreaks of hemolysis in hemodialysis patients have occurred when chloramines in the public water supply have not been adequately removed by the dialysis unit's water purification system. Chloramines are not removed by reverse osmosis or deionization, and need to be either adsorbed by filtration through granular activated carbon (GAC) or neutralized by chemical reduction by ascorbic acid (vitamin C) added to the dialysate. Chloramine levels in the incoming water can fluctuate unpredictably, and failures of both systems have occurred when chloramines have exhausted their capacity. The medical and technical issues associated with both methods are explored in detail. Safety depends on critical care in the design of the system and rigorous testing more than once daily. Most dialysis units now depend on GAC filters, two of which should be placed in series so that chloramine breakthrough can be detected after the first one, before the second one fails. Comprehensive standards in force in California have not yet been applied universally.

Blood↗

Influence of temperature, pH, oxygenation, water-type and substrate on biomarker responses in the freshwater clam Corbicula fluminea (Müller).

We investigated the influence of abiotic factors on responses of components of detoxification metabolism of phases I and II, indicators related to oxidative stress and propionylcholinesterase, proposed as biomarkers of pollution in Corbicula fluminea. Combined effects of temperature (10 and 20 degrees C), water-type (water purified by reverse-osmosis, lake water from the collection site and tap water) and habitat substrate (presence and absence of sand) were assessed in a five-day experiment. Additionally, clams were exposed to hypoxia or submitted to acidic, neutral or alkaline conditions at 20 degrees C, in lake water, without sand, for five days. Responses of biomarkers were generally higher when clams were placed in tap water, except for level of peroxidised lipids (PL). Catalase (CAT) and NADH-cytochrome c reductase (NADH-red.) activities increased whereas propionylcholinesterase (PChE) activity decreased in absence of sand. Decreasing temperature resulted in depressing PChE and NADPH-cytochrome c reductase (NADPH-red.) activities. Hypoxia induced an increase of CAT activity and glutathione S-transferase activity towards ethacrynic acid and a decrease of PL level. CAT and NADH-red. activities as well as PL level were reduced when clams were exposed to acidic and/or alkaline conditions. These results indicate that effects of abiotic factors should be taken into account in environmental studies.

Analysis of Variance↗