PubMed HealthSearch

Biomedical subjects

D E Wurster

Publications and source records attributed to D E Wurster.

At least 19 recordsLinked to original sources

Stability of undiluted and diluted adenosine at three temperatures in syringes and bags.

The stability of adenosine in various diluents in polypropylene syringes and polyvinyl chloride (PVC) bags at three temperatures was studied. Portions of pooled undiluted adenosine infusion (3 mg/ mL) were stored in 60-mL capped syringes, 20 for each storage condition. Adenosine infusions were prepared by mixing adenosine with 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer's injection, or 5% dextrose and lactated Ringer's injection to produce a concentration of 0.75 mg/mL. Samples of each infusion were stored in 60-mL capped syringes and 50-mL bags, 20 syringes and 20 bags for each storage condition. Syringes and bags were stored in the dark at 25, 5, and -15 degrees C. At various sampling times, three syringes and three bags of each infusion were removed for visual inspection, pH measurement, and high-performance liquid chromatographic analysis. At 10 and 16 days, fungal growth at 25 degrees C was suspected in the infusions prepared with 5% dextrose injection. For all other samples, there was no evidence of precipitation or change in pH. The concentration of adenosine remained constant in all samples at all storage conditions. Adenosine 3 mg/mL was stable in polypropylene syringes for 7 days at 25 degrees C, 14 days at 5 degrees C, and 28 days at -15 degrees C; adenosine 0.75 mg/ mL in 0.9% sodium chloride injection and in 5% dextrose injection was stable in polypropylene syringes and PVC bags for 16 days at 25, 5, and -15 degrees C; and adenosine 0.75 mg/mL in lactated Ringer's injection and in 5% dextrose and lactated Ringer's injection was stable in syringes and bags for 14 days at 25, 5, and -15 degrees C.

Adenosine

Significance of melanin binding and metabolism in the activity of 5-acetoxyacetylimino-4-methyl-delta2-1,3,4,-thiadiazolin e-2-sulfonamide.

5-Acetoxyacetylimino-4-methyl-delta2-1,3,4,-thiadiazoline -2-sulfonamide (compound (1)) is an ester prodrug that lowered intraocular pressure (IOP) in albino New Zealand rabbits, but was found to be inactive in pigmented Dutch Belt rabbits. In order to explain the differences in pharmacological activity for the two rabbit species, metabolism and melanin binding were studied. Depending on the initial concentration, the binding of compound (1) to natural melanin (Sepia officinalis) was 20-60%. The binding constant, K, at 37 degrees C was 4.32 x 10(5) M(-1) and the maximum moles bound to melanin, r(max), was 4.5 x 10(-7) mol/mg of melanin. From a determination of binding at temperatures between 25 degrees C and 47 degrees C, a van't Hoff plot was constructed to determine enthalpy and entropy changes accompanying the binding process, deltaH and deltaS, respectively. Values calculated from the plot were -12.7 and -15.4 kcal/(mol deg), respectively. Negative values for these parameters are consistent with charge transfer interactions and therefore suggest that this may be an operative mechanism between compound (1) and melanin. The in vitro incubation of compound (1) was also studied with various ocular tissues from both albino and pigmented rabbits which were iris-ciliary body, intact cornea, stroma/endothelium and aqueous humor. A major metabolite, MET 1, was identified and also observed from in vivo analyses of the same tissues following topical application. The metabolite was isolated and subjected to mass spectroscopy and proton nuclear magnetic resonance spectroscopy analysis. From these analyses, it was hypothesized that the formation of MET 1 involved a GSH conjugation mechanism which displaced the sufonamide (-SO2NH2) group. The metabolism was found to be less extensive in the pigmented rabbit than in the albino rabbit and suggested that the binding affinity of compound (1) for melanin was a better explanation for the lack of IOP activity in the pigmented rabbit than differences in metabolism.

Animals

Use of Fourier transform infrared (FTIR) spectroscopy to follow the adsorption of heptane and 1,4-dioxane vapors on a zinc oxide surface.

Vapor adsorption isotherms of two nonpolar model compounds, heptane and 1,4-dioxane, were determined for a very small particle size zinc oxide (ZnO) powder (median particle size approximately 23 nm) in the lower relative vapor pressure (P/Po) region. The ZnO samples for all adsorption measurements were dried at 400 degrees C for 4 h. A new method, which employed an FTIR spectrometer with a long path gas cell (IR path length of 3.0 m), was developed for the organic vapor adsorption measurements. The amount adsorbed was determined by mass balance. This method allows accurate quantification of organic vapors and is sensitive to very low P/Po values. The heptane and 1, 4-dioxane vapor adsorption isotherms appeared to exhibit the expected Type II behavior. The surface areas obtained for ZnO from BET analyses of the heptane and 1,4-dioxane vapor adsorption isotherms (36.9 and 30.3 m2/g) compared reasonably well to the surface area obtained from BET analysis of the nitrogen vapor adsorption isotherm (32.6 m2/g). The amount of vapor adsorbed by ZnO at P/Po equal to 0.1, in terms of number of moles, was observed to decrease in the order: water10 >> 1,4-dioxane > heptane. It was inferred that, while heptane was only adsorbed via a dipole-induced dipole interaction, 1,4-dioxane was physically adsorbed via an interaction dominated by the oxygen lone-pair orbital. Presumably, this interaction was more comparable to a weak dipole-dipole interaction. These results are consistent with the expected strengths of interaction.

Dioxanes

The influence of tear proteins on the film stability of rabbit tear extracts.

This study was undertaken to gain an understanding of the significance of tear proteins in stabilizing the tear film. Either a sigma agonist, N,N-dimethyl-2-phenylethylamine HCl (AF2975), or a sigma antagonist, haloperidol, was administered to rabbit eyes in order to increase or decrease protein secretion, respectively. At 0, 10 and 60 minutes after instillation, tear proteins were extracted from Schirmer strips and measured for total protein. A portion of the extract was used for separating five major protein fractions using size-exclusion HPLC. Total protein extract or individual protein fractions were measured for surface tension by the horizontal capillary method and for in vitro break up time (in vitro BUT), a newly designed procedure. A statistically significant decrease was measured for surface tension and a concomitant increase was measured for in vitro BUT for the total protein samples at 10 and 60 minutes after instillation of AF2975 compared to the vehicle treated eye. The results for haloperidol yielded an increase in surface tension and an decrease in in vitro BUT. When the tear proteins were separated into five major fractions, only the 23 minute protein fraction was found to decrease surface tension and increase in vitro BUT following AF2975 administration. Haloperidol, a sigma antagonist, showed an exact opposite effect for the total protein and the 23 minute protein fraction.

Animals

Determination of diffusion coefficients of sodium p-aminosalicylate in sheep nasal mucosae and dialysis membranes by Fourier transform infrared horizontal attenuated total reflectance spectroscopy.

Fourier transform infrared horizontal attentuated total reflectance (FT-IR-H-ATR) spectroscopy was employed to determine the diffusion coefficients of sodium p-aminosalicylate (PAS) in sheep nasal mucosae and dialysis membranes. The system configuration, which comprises a closed system with an aqueous layer and a membrane layer, represents diffusion from a solution of limited volume. Data analysis involved fitting a truncated (seven term) Fourier series to the total mass transport into the membrane as a function of time. Comparison of diffusion coefficients of PAS in dialysis membranes obtained by this technique to those obtained by a standard steady-state permeation method showed excellent agreement. Apparent diffusion coefficients were approximately 4.33 (+/- 0.38) x 10(-7) and approximately 9.62 (+/- 5.30) x 10(-7) cm2/s for dialysis membranes and sheep nasal mucosae, respectively. These values are substantially smaller than the diffusion coefficient of PAS in aqueous solution, indicating that the rate-limiting step was diffusion in the membrane. The effect of purified gastric mucin solution (concentration up to approximately 6% w/v) on the apparent diffusion coefficient of PAS in the membranes was also investigated. The results showed no statistically significant change in the apparent diffusion coefficient in the presence of mucin for either sheep nasal mucosae or dialysis membranes. Although it was reported that mucin in solution retards the diffusion of PAS as compared to buffer alone, the mass transport within the membrane was the rate-limiting step for this hydrophilic compound.

Aminosalicylic Acid

Tear film stability of protein extracts from dry eye patients administered a sigma agonist.

Fourteen dry eye volunteers placed one to two drops of 0.15% AF2975 (N,N-dimethyl-2-phenylethylamine HCl) in one eye and the vehicle in their other eye four times a day for 21 days. AF2975 is a sigma agonist known to stimulate the release of tear proteins after instillation in rabbit eyes and was tested for its ability to stabilize protein film extracted from dry eye volunteers. After day 7 and again after day 21, Schirmer test strips were inserted in each eye for 5 minutes, measured for wetting, and stored at -20 degrees C for protein analysis. A volume of 600 microliters was used to extract total protein. A portion of the extract was analyzed for total protein. The remainder was used to measure surface tension, to determine in vitro break up time (in vitro BUT) in a newly designed apparatus, and to further analyze for tear lipocalin, formerly known as presystemic tear albumin. Statistically significant differences were obtained between the drug treated eye and the vehicle treated eye for measurements determined for days 7 and 21. Tear extracts from the drug treated eye showed statistically significant decreases in surface tension and increases in in vitro BUT. Extracts from the drug treated eye also showed statistically significant increases in protein content and tear lipocalin. The results suggest that AF2975 may be able to stabilize the tear film by increasing the concentration of proteins in human tears.

Adult

The effect of composition on the tableting indices of binary powder mixtures.

The purpose of this study was to investigate the effect of the composition of a binary powder mixture on the bonding index, the brittle fracture index, and the strain index, as defined by Hiestand. The studies involved tensile strength and dynamic indentation hardness determinations of square compacts, the solid fractions of which were 0.83. The mixtures were such that both components consolidated by plastic deformation, both components consolidated by brittle fracture, or one component was brittle while the other was plastic. The measured quantities were then used to compute the bonding index, the brittle fracture index, and the strain index. The bonding indices and tensile strengths of the individual plastic materials were greater than those of the individual brittle materials. It was concluded that the bonding indices were linearly related to composition when both materials consolidated by the same mechanism. It was further concluded that the bonding indices were related to compact composition by a second-degree polynomial equation for mixtures with one brittle and one plastic component. This latter relationship was consistent for four pairs of components.

Lactose

Pressure-induced activity loss in solid state catalase.

The pressure-induced reductions in the activities of a number of enzymes in the solution state, and more recently in the solid state, have been reported. To further investigate the effect of pressure on proteins in the solid state, the enzyme catalase was used as a model. Compacts containing 150.0 +/- 0.2 mg of catalase powder were prepared on instrumented laboratory presses using various compaction pressures between 0 and 669 MPa. After compaction, a spectrophotometric assay was utilized to determine the pseudo-first-order rate constants for the catalase-catalyzed decomposition of hydrogen peroxide. These rate constants were used to calculate the change in catalase activity. Results indicated a loss in catalase activity of up to 30% at compaction pressures of 251 MPa or greater. While the mechanism which produces the loss of enzyme activity is not clear, a strong linear correlation between enzyme activity and compaction pressure was seen over the range of pressures (0-251 MPa) where the decrease in activity occurred. In addition, compact densities were calculated and correlated to enzyme activity values. This correlation did not appear to be as strong.

Animals

Determination of the mechanism for the decrease in zinc oxide surface area upon high-temperature drying.

High-temperature drying is required to remove chemisorbed water from the zinc oxide surface. High-temperature drying of a very small particle size zinc oxide powder (median particle size approximately 23 nm) resulted in a substantial decrease in the surface area. The surface areas (BET analysis of 77 K nitrogen vapor adsorption data) of ZnO samples dried at 500 degrees C decreased continually as the drying time was increased. Although the surface area decrease was fastest during the first 5 h, a 64% decrease in surface area was found after 20 h. The decrease in surface area was not due to a collapse of pore structure. Comparison of nitrogen vapor adsorption and desorption isotherms as well as geometric calculations of surface area indicated that both the original and final particles were nonporous. X-ray diffractograms of the original powder and of powders dried at two temperatures were all identical. Thus, no change in crystal structure occurred as a result of drying at 500 degrees C. Atomic force microscopy provided substantial evidence that the surface area decrease was due to a shift in the particle size distribution to a larger mean size. It was verified using two different experiments that ZnO exhibited significant sublimation at 500 degrees C. It was concluded that the increase in particle size was due to a sublimation/condensation process that obeyed the Kelvin equation. The effect of ZnO particle size on the vapor pressure ratio in the Kelvin equation was modeled at 500 degrees C for several different assumed solid surface tensions. Drying conditions for ZnO were then selected which balanced maximum removal of chemisorbed water and minimum surface area decrease. Water vapor adsorption isotherms for ZnO at 25 degrees C were subsequently obtained. Differences in the isotherms resulting from the presence or absence of a chemisorption contribution could clearly be demonstrated.

Adsorption

Computer modeling of adsorption on an activated charcoal surface.

The molecular modeling program SYBYL was used to simulate the adsorption of various barbiturates by an activated charcoal surface. The compounds barbituric acid (BA), barbital (B), phenobarbital (PB), mephobarbital (M), and primidone (Pr) were modeled, and their structures were energetically minimized. These structures agreed with literature reports for the conformations of these molecules in dimethyl sulfoxide-d6, methanol-d4, and chloroform-d. The activated charcoal surface was modeled using graphitic crystallites which had either no oxygen-containing functional group, a C-OH functional group, or a C = O functional group. The presence of the C-O (presumably C-OH) and C = O functional states on activated charcoal surfaces had been previously determined by X-ray photoelectron spectroscopy. It was assumed that the crystallite was locally flat. Upon docking, conformational changes were observed for barbital, phenobarbital, mephobarbital, and primidone. Estimates for the heat of adsorption ranged from -62.3 kJ/mol for barbituric acid to -91.1 kJ/mol for mephobarbital on the hydroxylated surface. Allowance for the heat of desorption of the required number of water molecules from the surface, also determined by SYBYL, gave heat of displacement values of -19.4 kJ/mol for barbituric acid and -32.6 kJ/mol for mephobarbital. These values compared well to the heat of displacement values obtained by isoperibol calorimetry, which were -20.3 kJ/mol for barbituric acid and -31.6 kJ/mol for mephobarbital. Previous laboratory studies had demonstrated the greater importance of the C-O functional state for barbiturate adsorption compared to the C = O functional state. The computer-modeled system predicted the same result.

Adsorption

The use of Fourier transform infrared (FT-IR) spectroscopy to determine the diffusion coefficients of alcohols in polydimethylsiloxane.

A variable long path gas cell was used to measure the sorption of organic vapors by a polymer slab. Unfilled polydimethylsiloxane (PDMS) slabs were cast and used to study the sorption of a series of aliphatic alcohols. The PDMS slab was suspended in the gas cell and exposed to low relative pressures of an alcohol vapor. The sorption rate of the alcohol vapor by the PDMS slab was obtained by measuring the decrease in the amount of free diffusant in the gas cell. The diffusion coefficients of the alcohols in the PDMS slab were then calculated from the curves of amount of diffusant sorbed versus time. The results show that the values of the diffusion coefficients at nearly infinite dilution, D0, for methanol, ethanol, 1-propanol, and 1-butanol are 1.01 x 10(-5), 0.61 x 10(-5), 0.54 x 10(-5), and 0.33 x 10(-5) cm2/sec, respectively. The isotherms for the sorption of the alcohols by the PDMS slab were also constructed from the data.

Adsorption

Phenobarbital removal characteristics of three brands of activated charcoals: a system analysis approach.

The in vivo phenobarbital removal characteristics of three brands of activated charcoal (Actidose, Charcoaid, Superchar) were studied in normal volunteers using a system analysis approach. The subjects received a 200-mg dose of oral or intravenous phenobarbital followed by a single oral dose of 30 g of one of the three charcoals in a randomized crossover design. The relative merits of the three charcoals in enhancing the removal of oral and intravenous phenobarbital were assessed using a system analysis approach. The removal clearance, time to peak (tp), peak removal clearance (Rmax), percentage of dose removed (PCT infinity), and phenobarbital removal clearance (CLr) were calculated for the oral and intravenous treatments. Superchar had a pulse-like effect, with the shortest tp and the largest Rmax. Actidose and Charcoaid had similar effects, with Actidose inducing slightly greater phenobarbital removal. Superchar has the highest surface area and relative percentage of surface hydroxyl groups, whereas Actidose has the lowest surface area and relative percentage of surface hydroxyl groups of the three charcoals studied. Although correlations between the in vitro and the in vivo phenobarbital adsorption characteristics of the three charcoals may be difficult due to the presence of preservatives and palatibility enhancers in the commercial preparations, it appears that the in vivo effectiveness decreases as the surface area and the concentration of surface hydroxyl groups decrease. The proposed system analysis approach requires fewer assumptions than methods based on compartmental or physiologic approaches and has the advantage of describing the phenobarbital removal in a dynamic manner.

Absorption

The determination of diffusion coefficients in semisolids by Fourier transform infrared (FT-IR) spectroscopy.

A Fourier transform infrared (FT-IR) spectrometer with a horizontal attenuated total reflectance (ATR) cell was used to determine the diffusion coefficients of several liquids in two semisolid materials. The experimental setup was that of a system with one open and one closed boundary wherein the open boundary was maintained at constant concentration. While the liquid of interest was diffusing through the film of ointment, the concentration of liquid at the film surface in contact with the ATR crystal was determined at various times by means of IR absorption measurements. The depth of penetration of the IR radiation into the sample was approximately 0.6-0.9 microns at the wavelengths of analysis. Since the ointment thickness was 157 microns, it was reasonable to assume that only the penetrant reaching the lower boundary was being measured. The values of the diffusion coefficients were then calculated using an equation that appropriately modeled the aforementioned conditions. The liquids tested exhibited diffusion coefficients in anhydrous lanolin and in polyethylene glycol ointment that ranged from 0.56 to 7.2 x 10(-7) and 0.68 to 5.7 x 10(-7) cm2/sec, respectively. The expected molecular weight dependency was observed.

Diffusion

Surface characterization of activated charcoal by X-ray photoelectron spectroscopy (XPS): correlation with phenobarbital adsorption data.

X-ray photoelectron spectroscopy (XPS) was used to identify the functional states of carbon existing on the surfaces of various activated charcoals. The relative percentages of carbon, oxygen, and detectable trace elements comprising the activated charcoal surfaces were determined. Analysis of the carbon core-electron binding energy region revealed the existence of one hydrocarbon state (C-H, C-C are indistinguishable) and three oxygen-containing functional states. These states were hydroxyls or ethers (C-O), carbonyls (C = O), and carboxylic acids or esters (O-C = O). The C-O functional state contributed approximately 60-70% to the total percentage of oxygen-containing states. A very good correlation existed between the apparent areas occupied on the adsorbent surface per phenobarbital molecule and the relative percentages of the C-O functional state. Previously reported heat of displacement results for phenobarbital adsorption are now explained since the C-O state appears to be the primary site involved in the binding of phenobarbital by the activated charcoals.

Adsorption

Model selection for the adsorption of phenobarbital by activated charcoal.

Activated charcoal is known to adsorb a wide variety of substances from solution, and several equations have been used to fit the resulting adsorption data. The determination of the correct model to fit phenobarbital adsorption onto activated charcoal was made using a calorimetric method. The differential heats of displacement of water by phenobarbital for four activated charcoals were determined and found to be linearly related to the amount of phenobarbital adsorbed. The activated charcoals studied had statistically similar heats of displacement. The linear relationship between heat evolved and the amount of phenobarbital adsorbed is consistent with the assumptions implicit in the Langmuir model.

Adsorption

Catalysis of carbaryl hydrolysis in micellar solutions of cetyltrimethylammonium bromide.

Carbaryl hydrolysis was studied in micellar solutions of cetyltrimethylammonium bromide (CTAB) at pH 7.5 The hydrolysis followed first-order kinetics with respect to carbaryl concentration. Above the critical micelle concentration (CMC) the rate of hydrolysis increased with increasing CTAB concentration. A plateau was ultimately reached, at which the rate constant was 30 times the rate constant in an equivalent solution without CTAB. Entropies of activation were calculated to prove that the reaction mechanism did not change in the micellar environment. The binding constant of the micelle for carbaryl and the rate constant in the micellar pseudophase were determined from kinetic data using the pseudophase model. To verify this binding constant, a study of the solubility of carbaryl in CTAB solutions was performed. The results were found to be in very good agreement with those from the kinetic studies.

Algorithms