Switchable long-range double layer force observed in a protic ionic liquid.

A repulsive double layer force has been measured for ethylammonium nitrate (EAN) at 373 K and 393 K, which is absent at lower temperatures. This temperature-tuneable change in behaviour is the opposite of recent observations which challenge traditional views of ionicity. This finding thus widens the debate about the very nature of ionic liquids.

Tribotronic control of friction in oil-based lubricants with ionic liquid additives.

Atomic force microscopy (AFM) reveals that tribotronic control of friction using an external potential applied to a gold surface is possible for ionic liquid (IL) concentrations as low as 5 mol% in hexadecane. The IL used is trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate, in which both the cation and anion have surfactant-like structures, and is miscible with hexadecane in all proportions. For IL concentrations less than 5 mol% friction does not vary with applied potential, but for 5 mol% and above changing the potential changes the composition of the IL boundary layer from cation-enriched (negative potentials) to anion-enriched (positive potentials). As the lubricities of the cation-rich and anion-rich boundary layers differ, this enables active control of friction in oil-based lubricants.

Tactile friction of topical formulations.

BACKGROUND: The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. METHODS: Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. RESULTS: The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. CONCLUSION: The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations.

Can Cobalt(II) and Chromium(III) Ions Released from Joint Prostheses Influence the Friction Coefficient?

Cobalt chromium molybdenum alloys (CoCrMo) are commonly used as articulating components in joint prostheses. In this tribocorrosive environment, wear debris and metal ionic species are released and interact with proteins, possibly resulting in protein aggregation. This study aimed to investigate whether this could have an effect on the friction coefficient in a typical material couple, namely CoCrMo-on-polyethylene. It was confirmed that both Co(II) and Cr(III) ions, and their combination, at concentrations relevant for the metal release situation, resulted in protein aggregation and its concomitant precipitation, which increased the friction coefficient. Future studies should identify the clinical importance of these findings.

Note: Determination of torsional spring constant of atomic force microscopy cantilevers: combining normal spring constant and classical beam theory.

A technique has been developed for the calculation of torsional spring constants for AFM cantilevers based on the combination of the normal spring constant and plate/beam theory. It is easy to apply and allow the determination of torsional constants for stiff cantilevers where the thermal power spectrum is difficult to obtain due to the high resonance frequency and low signal/noise ratio. The applicability is shown to be general and this simple approach can thus be used to obtain torsional constants for any beam shaped cantilever.

Mixtures of n-dodecyl-beta-D-maltoside and hexaoxyethylene dodecyl ether--surface properties, bulk properties, foam films, and foams.

Mixtures of the two non-ionic surfactants hexaoxyethylene dodecyl ether (C(12)E(6)) and n-dodecyl-beta-D-maltoside (beta-C(12)G(2)) were studied with regard to surface properties, bulk properties, foam films, and foams. The reason for studying a mixture of an ethylene oxide (C(i)E(j)) and a sugar (C(n)G(m)) based surfactant is that despite being non-ionic, these two surfactants behave quite differently. Firstly, the physico-chemical properties of aqueous solutions of C(n)G(m) surfactants are less temperature-sensitive than those of C(i)E(j) solutions. Secondly, the surface charge density q(0) of foam films stabilized by C(n)G(m) surfactants is pH insensitive down to the so-called isoelectric point, while that of foam films stabilized by C(i)E(j) surfactants changes linearly with the pH. The third difference is related to interaction forces between solid surfaces. Under equilibrium conditions very high forces are needed to expel beta-C(12)G(2) from between thiolated gold surfaces, while for C(12)E(6) low loads are sufficient. Fourthly, the adsorption of C(12)E(6) and beta-C(12)G(2) on hydrophilic silica and titania, respectively, is inverted. While the surface excess of C(12)E(6) is large on silica and negligible on titania, beta-C(12)G(2) adsorbs very little on silica but has a large surface excess on titania. What is the reason for this different behaviour? Under similar conditions and for comparable head group sizes, it was found that the hydration of C(i)E(j) surfactants is one order of magnitude higher but on average much weaker than that of C(n)G(m) surfactants. Moreover, C(n)G(m) surfactants possess a rigid maltoside unit, while C(i)E(j) surfactants have a very flexible hydrophilic part. Indeed, most of the different properties mentioned above can be explained by the different hydration and the head group flexibilities. The intriguing question of how mixtures of C(i)E(j) and C(n)G(m) surfactants would behave arises organically. Thus various properties of C(12)E(6)+beta-C(12)G(2) mixtures in aqueous solution have been studied with a focus on the 1:1 mixture. The results are compared with those of the single surfactants and are discussed accordingly.

A method for assessment of blood volume parameters in pregnant sheep using fluorescein-labelled dextran.

The assessment of blood volume parameters in clinical and research settings has been limited by methods that involve radioactivity, complex assays or are unreliable. We aimed to design a method for measuring blood volume parameters that was non-radioactive, simple, cheap and reliable. We have used a commercially available fluorescein-labelled 250kDa dextran, a large inert molecule, and have measured dilution of this through the intravascular space of pregnant ewes. From this estimation of plasma volume and measured hematocrit, we have calculated blood volume and red cell volume. The blood volume results are 6% lower than those obtained using radiolabelled red cells, but there is no significant difference in red cell volume between methods. The coefficient of variation for repeated measurements of plasma volume measurements is 3.8%. This is a simple, reliable, cheap and non-radioactive method for estimating blood volume parameters in pregnant sheep, and may prove useful in other settings.

Adhesion forces between protein layers studied by means of atomic force microscopy.

Adhesion forces between different protein layers adsorbed on different substrates in aqueous media have been measured by means of an atomic force microscope using the colloid probe technique. The effects of the loading force, the salt concentration and pH of the medium, and the electrolyte type on the strength, the pull-off distance, and the separation energy of such adhesion forces have been analyzed in depth. Two very different proteins (bovine serum albumin and apoferritin) and two dissimilar substrates (silica and polystyrene) were used in the experiments. The results clearly point out a very important contribution of the electrostatic interactions in the adhesion between protein layers.

Existence of hydration forces in the interaction between apoferritin molecules adsorbed on silica surfaces.

The atomic force microscope, together with the colloid probe technique, has become a very useful instrument to measure interaction forces between two surfaces. Its potential has been exploited in this work to study the interaction between protein (apoferritin) layers adsorbed on silica surfaces and to analyze the effect of the medium conditions (pH, salt concentration, salt type) on such interactions. It has been observed that the interaction at low salt concentrations is dominated by electrical double layer (at large distances) and steric forces (at short distances), the latter being due to compression of the protein layers. The DLVO theory fits these experimental data quite well. However, a non-DLVO repulsive interaction, prior to contact of the protein layers, is observed at high salt concentration above the isoelectric point of the protein. This behavior could be explained if the presence of hydration forces in the system is assumed. The inclusion of a hydration term in the DLVO theory (extended DLVO theory) gives rise to a better agreement between the theoretical fits and the experimental results. These results seem to suggest that the hydration forces play a very important role in the stability of the proteins in the physiological media.

Hydration forces between silica surfaces: experimental data and predictions from different theories.

Silica is a very interesting system that has been thoroughly studied in the last decades. One of the most outstanding characteristics of silica suspensions is their stability in solutions at high salt concentrations. In addition to that, measurements of direct-interaction forces between silica surfaces, obtained by different authors by means of surface force apparatus or atomic force microscope (AFM), reveal the existence of a strong repulsive interaction at short distances (below 2 nm) that decays exponentially. These results cannot be explained in terms of the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, which only considers two types of forces: the electrical double-layer repulsion and the London-van der Waals attraction. Although there is a controversy about the origin of the short-range repulsive force, the existence of a structured layer of water molecules at the silica surface is the most accepted explanation for it. The overlap of structured water layers of different surfaces leads to repulsive forces, which are known as hydration forces. This assumption is based on the very hydrophilic nature of silica. Different theories have been developed in order to reproduce the exponentially decaying behavior (as a function of the separation distance) of the hydration forces. Different mechanisms for the formation of the structured water layer around the silica surfaces are considered by each theory. By the aid of an AFM and the colloid probe technique, the interaction forces between silica surfaces have been measured directly at different pH values and salt concentrations. The results confirm the presence of the short-range repulsion at any experimental condition (even at high salt concentration). A comparison between the experimental data and theoretical fits obtained from different theories has been performed in order to elucidate the nature of this non-DLVO repulsive force.

Paget's disease of bone in New Zealand: continued decline in disease severity.

We have reported previously that severe Paget's disease of bone had become less common at our center between 1973 and 1993. Data from several countries support the view that there are important secular trends in the prevalence and severity of Paget's disease. In this paper we describe recent trends in the demography of newly referred patients with Paget's disease to determine if the secular trend toward milder disease has continued. A database of all newly referred patients (n = 1487) with Paget's disease (1973 to 2002 inclusive, 30 years) was examined. Of these, 832 subjects (56%) had scintiscans. Plasma total alkaline phosphatase (total ALP) activity, disease extent on scintiscan, and a derived index of average ALP activity of pagetic bone were used as indices of severity. The number of new referrals with Paget's disease declined sharply from 1994 onward and is currently at half the rate seen 20 years earlier, while the mean age at presentation has progressively increased by 4 years per decade (P < 0.0001). Total ALP at diagnosis, disease extent on scintiscan, and the number of bones involved were all negatively correlated with both date of birth (P < 0.0001) and year of presentation (P < 0.0001), indicating that more recently born and presenting subjects had substantially less severe bone disease. The average activity of pagetic bone was only weakly correlated with year of presentation, but not with year of birth or age at presentation. Although there are a number of potential biases, these data are consistent with a continued secular trend to presentation in older subjects with less extensive skeletal involvement, and a declining prevalence of Paget's disease.

Database deconvolution.

A new deconvolution technique is described. It regards the Rutland-Patlak plot as the integral of the retention function, and performs deconvolution by creating and then differentiating the Rutland-Patlak plot. The reasoning behind this approach is that in producing the Rutland-Patlak plot, both the content function and the integral of the input function are divided by the input function (i.e. the blood curve), and that this has the effect of producing data equivalent to that which would be produced if the input function did not vary (i.e. if there were a constant blood level of tracer). The concept was tested against data created by modelling techniques. It was able to reproduce retention functions with a variety of different shapes that were used to produce the artificial renogram data. The new deconvolution method is sufficiently simple to be used in either a database or a spreadsheet and does not require any special program units to be written. It does not appear to make any assumptions about the data nor the shape of the retention function, and does not appear to be vulnerable to the oscillating errors that sometimes occur in iterative deconvolution.

Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.

It has been claimed that the bisphosphonate space, a scintigraphic technique which simultaneously estimates bone uptake and renal clearance of bisphosphonate, can be used to predict the dose of bisphosphonate required to induce biochemical remission in Paget's disease. In a prospective study of 15 newly diagnosed patients with Paget's disease, bisphosphonate space measurements were made prior to treatment with intravenous clodronate. Treatment with clodronate 0.6 g was given four times weekly until the alkaline phosphatase (ALP) suppressed below the upper level of the reference range (120 u/l) or reached a plateau, and the cumulative dose required (1.8-7.8 g) was calculated. Overall, the bisphosphonate space correlated poorly with the total dose requirement (r = 0.441, P = 0.100), but the relationship was weakened by an outlier, who had the poorest renal function. Excluding this subject improved the correlation coefficient (r = 0.852, P <0.0001). The relationship between dose requirement and log10 initial ALP was not as strong (r = 0.672, P <0.01). However, for both ALP and the bisphosphonate space the 95% prediction intervals were wide. We conclude that the bisphosphonate space does relate to dose requirements for intravenous bisphosphonates, but that it is unreliable when renal function is poor, and may not offer much gain over the pretreatment ALP levels. Both ALP and the bisphosphonate space have wide prediction intervals, and are therefore poor guides to dose requirement.

Mean transit times without deconvolution...reconsidered.

A new deconvolution technique is described. It is based on an earlier method which used a graphical technique to analyse the early stages of organ data and blood curves to obtain the background subtraction factor and the uptake constant for tracer uptake by the organ. In that initial application, those variables were then applied to a later point on the organ and blood curves to calculate a mean transit time without first producing a retention function. This new deconvolution technique performs that later step on all points of the organ data curve to produce a function showing how the mean transit time varies with time. This considered to be the area under the retention function (i.e. the integral of the retention function), and the retention function itself is then obtained by differentiation. Modelling techniques were used to create renogram shapes by convoluting known (input) retention functions with a calculated blood curve. The new deconvolution method was then used to recover the retention function from each artificial data curve. The recovery of that input data implies that the new deconvolution technique is sufficiently successful to justify further consideration. In addition, as a demonstration, iterative deconvolution and the new method were both used on renograms from an obstructed kidney and a kidney with normal outflow. Both methods produced similar shaped retention functions.

"FUR"--one size suits all.

This work used amalgamated data from previous projects in order to test the concept that when organ function is expressed in terms of tracer kinetics, the results are independent of patient size or gender. Dynamic gamma camera studies were analysed by measuring the rate of movement of tracers from the blood into various organs. These rates were expressed as a "fractional uptake rate" (FUR), which is the fraction of tracer in the blood taken up by the organ per unit time. As these values were small, it was convenient to express the FUR per million seconds. The FUR was calculated using the expression FUR = SLOPE (of Rutland-Patlak plot), multiplied by B(0) (the blood curve value back-extrapolated to time zero), and divided by the TOTAL amount of tracer injected. Data were used from adult patients between the ages of 20 and 49 years who had normal organ function. Organ/tracer groups studied were the skeletal uptake of 99mTc-MDP, the renal uptake of 99mTc-MAG3, the renal uptake of 99mTc-MDP, the renal uptake of 99mTc-DTPA, the hepatic uptake of 99mTc-colloid, the splenic uptake of 99mTc-colloid, and the hepatic uptake of 99mTc-DISIDA. Each organ/tracer group was divided into three subgroups according to patient size (smallest, middle and largest), and also into subgroups according to gender. Comparison of these subgroups did not show any significant size- or gender-related differences in FUR values. It is concluded that for patients with normally functioning organs the FUR is independent of patient size or gender. Thus, the FUR is a valuable way of expressing organ function, particularly in patients with unusual or rapidly changing body size, such as children.

Application of the JKR Method to the Measurement of Adhesion to Langmuir-Blodgett Cellulose Surfaces.

The JKR method has been applied for studying adhesion between poly(dimethylsiloxane) (PDMS) caps and Langmuir-Blodgett cellulose surfaces including the substrate, hydrophobized mica, and two flat mineral surfaces, bare mica and glass. The self-adhesion of PDMS caps and oxidized PDMS caps are included as a reference to compare with literature data. The results of the measurements have been compared with previous studies using the surface force apparatus and similar systems. A satisfactory agreement is obtained for simple systems showing no, or very limited, hysteresis between loading and unloading curves. In several cases, however, a large hysteresis is found between loading and unloading curves, with a larger adhesion measured from the pull-off force than from the JKR-curve determined on loading. This is, for instance, the case for PDMS against cellulose. The situation is analogous to that found in wetting studies showing a large hysteresis between advancing and receding contact angles. Copyright 2000 Academic Press.

Scintigraphic imaging of the hypoxia marker (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; prognox): noninvasive detection of tumor response to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid.

5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This study investigates, using mouse models, whether a new marker for tissue hypoxia, (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; Prognox)] has potential for the scintigraphic monitoring of tumor response to antivascular agents. Determination of radioactivity in dissected tissues 3 h after DMXAA (80 micromol/kg) or CA-4-P (227 micromol/kg) was injected indicated that both drugs inhibited blood flow (86RbCl uptake; 84 and 87%, respectively) and increased 99mTc-labeled HL-91 levels (350 and 300%, respectively) selectively in murine RIF-1 tumors. Planar imaging of 99mTc-labeled HL-91 3 h after DMXAA injection showed a dose-dependent increase in tumor levels above a threshold of 50 micromol/kg; this same threshold was observed for the inhibition of tumor blood flow (determined using Hoechst 33342). DMXAA also inhibited blood flow--and increased 99mTc-labeled HL-91 uptake--in MDAH-MCa-4 mouse mammary carcinomas and in NZMN10 human melanoma xenografts. Whether 99mTc-labeled HL-91 might also be useful as a biomarker for tumor cell killing was investigated by clonogenic assay of surviving cells 15 h after imaging 99mTc-labeled HL-91 in RIF-1 tumors. Log cell kill in individual tumors showed a statistically significant linear correlation (P < 0.001) with 99mTc-labeled HL-91 uptake after 60 micromol/kg (r2 = 0.79) and 70 micromol/kg (r2 = 0.44) but not at 80 micromol/kg DMXAA. The lack of correlation at high doses presumably reflects the insensitivity of the tumor-averaged 99mTc-labeled HL-91 signal to small regions in which tumor blood flow is preserved (which will limit log cell kill). The results indicate the potential of 99mTc-labeled HL-91 for the noninvasive imaging of tumor blood flow inhibition by antivascular drugs in humans.

Forces between Two Glass Surfaces with Adsorbed Hexadecyltrimethylammonium Salicylate.

Forces have been measured for hexadecyltrimethylammonium salicylate (C(16)TASal) layers on glass beads. During the inward process, hydrophobic attraction occurred at lower adsorption of C(16)TASal and electrostatic repulsion interactions happened at higher adsorption. While the jump-in phenomenon was observed for solutions of concentrations below the critical micelle concentration (cmc = 0.15 mM), the step-in phenomenon was characteristic for solutions at the cmc and above the cmc, suggesting the push-out of adsorbed C(16)TASal layers and/or inserted micelles. The remarkable pull-off phenomenon on the outward process occurred for all solutions, indicating a strong interaction between C(16)TASal molecules. For aqueous 0.15 mM C(16)TASal solutions of various NaSal concentrations, on the inward process, the electrostatic repulsive interaction decreased with adding NaSal. This is due to the electrostatic shielding by salt excess. The height of the force wall on the inward process reached a maximum at 0.01 M NaSal, but the interlocking between molecules on two surfaces during the outward process was minimized at 0.1 M NaSal. These tendencies, which are different from that of the electrostatic repulsion interaction, imply the strong cohesion between adsorbed C(16)TASal layers.

A comparison of the renal handling of 99Tcm-DTPA and 99Tcm-MAG3 in hypertensive patients using an uptake technique.

The renal uptake and outflow of 99Tcm-DTPA and 99Tcm-MAG3 were compared by analysing renal studies performed in two different departments, but with analysis techniques and computer programs using algorithms that were almost identical. Comparison was performed by a retrospective review of results from patients who were referred for renal investigations because of hypertension but who had apparently normal kidneys. The analysis of tracer outflow rates in the form of whole-kidney transit times and renal cortical transit times showed no significant difference between the two tracers. The fractional uptake rate of tracer for each patient (both kidneys) indicated that MAG3 was extracted from the blood 3.3 times faster than DTPA in patients aged 20-69 years, with a lower ratio above the age of 70. When used to measure relative renal function, there was no overall difference between the two tracers. The fractional uptake rates were also converted to flow rates, producing values of 95.8 +/- 28.0 ml.min(-1).1.73 m-2 for DTPA and 320 +/- 75 ml.min(-1).1.73 m-2 for MAG3, in hypertensive patients aged 20-40 years. These values showed a good correlation with other published GFR and MAG3 clearance rates (obtained using blood sampling methods) in normal patients of similar ages.