A novel option for dosing of proton pump inhibitors: dispersion of lansoprazole orally disintegrating tablet in water via oral syringe.

BACKGROUND: A new formulation of lansoprazole, the lansoprazole orally disintegrating tablet, rapidly disintegrates in water eliminating the need for swallowing whole pills. AIM: To assess the effect that dispersing the lansoprazole orally disintegrating tablet in water would have on lansoprazole pharmacokinetics. METHODS: Forty healthy adult men and women (18-43 years) received two single 15 mg lansoprazole orally disintegrating tablet doses separated by 3 days (one administered directly onto the tongue without water and one dispersed in water and administered orally via syringe) in a randomized, crossover fashion. Serial plasma samples were determined from 0 to 12 h for each dose. Ratios of central values for peak plasma exposure (C(max)) and mean overall extent of exposure (area under the plasma concentration) were used to compare the bioavailability. RESULTS: The two dosing regimens were bioequivalent, with the point estimate for area under the plasma concentration equalling 1.080 (confidence interval 1.012-1.152) and the point estimate for C(max) equalling 1.082 (confidence interval 0.961-1.218). CONCLUSIONS: Dispersing the 15 mg lansoprazole orally disintegrating tablet in water and administering the dose orally via syringe is bioequivalent to the 15 mg intact lansoprazole orally disintegrating tablet with respect to lansoprazole area under the plasma concentration and C(max). This dosing route provides an additional, convenient dosing option for lansoprazole.

Factors influencing red expression in autumn foliage of sugar maple trees.

We evaluated factors influencing the development of autumn red coloration in leaves of sugar maple (Acer saccharum Marsh.) by measuring mineral nutrient and carbohydrate concentrations, water content, and phenology of color development of leaves from 16 mature open-grown trees on 12 dates from June through October 1999. Mean foliar nutrient and carbohydrate concentrations and water content were generally within the range published for healthy sugar maple trees. However, foliar nitrogen (N) concentrations were near deficiency values for some trees. The timing and extent of red leaf coloration was consistently correlated with both foliar N concentrations and starch or sugar concentrations, which also varied with N status. Leaves of trees with low foliar N concentrations turned red earlier and more completely than those of trees with high foliar N concentrations. Low-N trees also had higher foliar starch concentrations than high-N trees. During the autumn development of red leaf coloration, foliar starch, glucose and fructose concentrations were positively correlated with red leaf color expression. At peak red expression, the concentrations of glucose, fructose, sucrose and stachyose were all positively correlated with red color expressed as a percent of total leaf area.

Seasonal patterns of carbohydrate reserves in red spruce seedlings.

We studied seasonal dynamics of carbohydrate storage in red spruce (Picea rubens Sarg.) seedlings by measuring starch and sugar concentrations of old needles (>/= one year old), new needles (< one year old), stems, and roots in two stands in the Green Mountains of Vermont. Although the two stands differed in many site characteristics including percent slope, aspect, soil type, drainage, and 564 m in elevation, concentrations and seasonal patterns of carbohydrates were similar for the two stands. For all tissues, starch concentrations peaked in late spring, declined through summer, and reached a minimum in winter. Sugar concentrations were greater than starch concentrations in all months except May and June. Sugar concentrations peaked in winter, and old needles showed a significant increase in sugar concentration between February and March. This increase in sugar concentration occurred without any reduction in localized starch concentrations or reductions in sugar or starch concentrations in new needles, stems or roots. Because March measurements were made toward the end of a prolonged thaw, a time when increases in photosynthesis have been documented for red spruce, it is likely that the March increase in sugar concentrations resulted from photosynthesis during the thaw. Compared with stems and roots, needles generally contained the highest concentration of carbohydrates and exhibited the greatest seasonal change in carbohydrate concentration. Needles were also the largest reservoir of carbohydrates throughout the year, especially during winter. Because of the critical roles of needles in photosynthesis and storage of carbohydrates, we conclude that any factors that disrupt the accumulation or availability of carbohydrates in red spruce needles will greatly alter plant carbon relations.

Capillary electrophoresis and capillary electrochromatography of organic pollutants.

Capillary electrophoresis (CE) has a unique capability for separation of analytes of environmental concern, particularly those that are more polar and ionic, based on the complementary separation principle of electrophoresis. In the past few years, CE has been selectively used to analyze various classes of compounds having current or potential environmental relevance. This review outlines the current status of CE for the determination of environmental pollutants, based predominantly on research results published from the beginning of 1997 to early 1999. Covered are environmental pollutants of all types except pesticides and inorganics. Certain naturally produced toxins are also covered because of their significant impacts upon human health and the environment. CE methods, as with all methods, must be judged on their ability to provide approaches that are reliable, sensitive, selective, and rapid, while meeting "green chemistry" initiatives for pollution prevention. We also compare CE methods to benchmark environmental techniques involving gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and high performance liquid chromatography (HPLC).

Capillary electrophoresis/laser-induced fluorescence detection of fluorescein as a groundwater migration tracer.

Capillary electrophoresis (CE) has been applied to the determination of the groundwater migration tracer dye fluorescein based on laser-induced fluorescence (LIF) detection and compared to determinations obtained with traditional spectrofluorimetry. Detection limits of injected dye in the low parts per trillion (ppt) ranges have been accomplished with both CE/LIF based on the Ar ion laser and with a spectrofluorimeter. This approach was used for a real-world problem in determining groundwater migration between adjacent Resource Conservation and Recovery Act (RCRA) and Superfund sites by the Environmental Sciences Division in response to regional needs and as application of new analytical tools under development. Fluorescent dye was injected into source wells and then was determined in monitoring wells by extracting pads that adsorbed the dye or by directly determining the dye in the water using solid-phase extraction (SPE), a preconcentration technique. The approaches based on CE/LIF exhibits increased specificity over existing approaches due to the separation and unique migration time of the dye. Additional studies were aimed at achieving sub-ppt levels in the water using solid-phase extraction and field-amplified injection techniques.

Identification of pollutants in a municipal well using high resolution mass spectrometry.

An elevated incidence of childhood cancer was observed near a contaminated site. Trace amounts of several isomeric compounds were detected by gas chromatography/mass spectrometry (GC/MS) in a concentrated extract of municipal well water. No matching library mass spectra were found and Fourier transform IR and NMR analyses were not feasible due to the low concentration of the compounds. Mass peak profiling from selected-ion-recording data (MPPSIRD) provided the sensitivity and scan speed necessary to acquire mass peak profiles at mass resolutions of 10,000 to 20,000 for the molecular ion (M+) and 10 fragment ions as capillary GC peaks eluted. Using a profile generation model (PGM), the elemental composition of the molecular ion was determined from the exact masses and abundances of the M, M + 1 and M + 2 profiles. Fragment ion compositions were determined from their exact masses based on the elements in the molecular ion. Exact mass differences between the molecular and fragment ions corresponded to unique combinations of atoms for the neutral losses. Consequent reduction of the number of possible structures for the fragment ions simplified mass spectral interpretation. After inspecting library mass spectra for smaller molecules, isomeric structures were hypothesized with cyano and alkylcyano groups attached to tetralin. A literature search found such isomers produced by an industrial polymer synthesis. Three isomers in a standard form polymerization of styrene and acrylonitrile provided the same mass spectra and GC retention times as isomers in the extract.

Photosynthetic capacity of red spruce during winter.

We measured the photosynthetic capacity (P(max)) of plantation-grown red spruce (Picea rubens Sarg.) during two winter seasons (1993-94 and 1994-95) and monitored field photosynthesis of these trees during one winter (1993-94). We also measured P(max) for mature montane trees from January through May 1995. Changes in P(max) and field photosynthesis closely paralleled seasonal changes in outdoor air temperature. However, during thaw periods, field photosynthesis was closely correlated with multiple-day temperature regimes, whereas P(max) was closely correlated with single-day fluctuations in temperature. There was a strong association between short-term changes in ambient temperature and P(max) during the extended thaw of January 1995. Significant increases in P(max) occurred within two days of the start of this thaw. Repeated measurements of cut shoots kept indoors indicated that temperature-induced increases in P(max) can occur within 3 h. Although significant correlations between P(max) and stomatal conductance (g(s)) or intracellular CO(2) concentration (C(i)) raised the possibility that increases in P(max) resulted from increases in stomatal aperture, fluctuations in g(s) or C(i) explained little of the overall variation in P(max). Following both natural and simulated thaws, P(max) increased considerably but plateaued at only 37% of the mean photosynthetic rate reported for red spruce during the growing season. Thus, even though shoots were provided with near-optimal environmental conditions, and despite thaw-induced changes in physiology, significant limitations to winter photosynthesis remained.

Modular methodology for determination of polychlorinated biphenyls in soil as Aroclors and individual congeners.

A comprehensive screening and confirmatory method was developed for monitoring polychlorinated biphenyls (PCBs), both as Aroclors and as individual congeners. This approach incorporates extraction, extract cleanup, and analysis modules designed to match cost, time, and data quality requirements. Soxhlet, sonication, supercritical fluid, and accelerated solvent extractions were evaluated. Carbon chromatographic cleanup procedures were used for separation of congeners on the basis of ortho substitutions, which permitted calculation of toxicity equivalents. Individual congener determinations, congener total histograms, and peak comparison techniques for Aroclor identification were elaborated by using high and low resolution mass spectrometric data. A screening procedure based on immunoassay using the Ohmicron PCB RaPID Assay kit gave results comparable to those obtained by gas chromatography with electron capture detection in the range 0.40-230 ppm, when the appropriate Aroclor calibrator was used.

Physiological changes in red spruce seedlings during a simulated winter thaw.

We evaluated net photosynthesis, respiration, leaf conductance, xylem pressure potential (XPP) and cold hardiness in red spruce (Picea rubens Sarg.) seedlings exposed to either a continuous thaw (CT) or a daytime thaw with freezing nights (FN) for 8 days during mid-winter. Physiological differences between CT and FN seedlings were evident for all measured parameters. However, the temporal expression of treatment differences varied among parameters. When compared to FN seedlings, CT seedlings had higher rates of respiration following 24 h of treatment, and a higher net photosynthetic rate, leaf conductance and XPP after 48 h of treatment. The CT seedlings were significantly less cold tolerant than the FN seedlings following 4 days of thaw, whereas FN seedlings did not deharden over the 8 days of treatment. Examination of temporal trends among thaw-associated changes in physiology suggested that, although greater carbon exchange occurred as stomatal conductance increased, the transition from negative to positive net photosynthesis was not the result of increases in conductance, but may have been associated with thaw-induced increases in XPP. Because thaw-associated changes in gas exchange and cold hardiness were offset in time, we conclude that, if changes in these processes are physiologically linked, the linkage is indirect.

Determination of elemental compositions from mass peak profiles of the molecular ion (m) and the m + 1 and m + 2 ions.

The relative abundances of M + 1 and M + 2 ions help to identify the elemental composition of the molecular ion (M). But scan speed, sensitivity, and resolution limitations of mass spectrometers have impeded determination of these abundances. Mass peak profiling from selected ion recording data (MPPSIRD) provided faster sampling and enhanced sensitivity, which permitted use of higher resolution. M + 2 profiles having only a few percent of the ion abundance of M were monitored at 20 000 resolution. The relative abundances, exact masses, and shapes of M, M + 1, and M + 2 mass peak profiles were determined. By applying five criteria based on these quantities, elemental compositions were determined even for ions too large (up to 766 Da) to be uniquely assigned from their exact mass and accuracy limits alone. A profile generation model (PGM) was written to predict these resolution-dependent quantities by considering all M + 1 and M + 2 ions for each candidate composition. The model also provided assurance that no other compositions were possible. Characterization of the M + 1 and M + 2 profiles by MPPSIRD and the PGM greatly expanded the practical ability of high-resolution mass spectrometry to determine elemental compositions.

Software-based mass spectral enhancement to remove interferences from spectra of unknowns.

Gas chromatography-mass spectrometry data from the analysis of complex environmental samples were converted into ASCII text and imported into a personal computer spreadsheet. A macro was written to perform mass spectral enhancement by statistical and mathematical procedures to separate the spectra of compounds of interest from interfering mass spectral responses, such as those of broadly eluting hydrocarbons. The extracted mass spectra were compared to reference spectra, with the result that usually 80-90% of the ions common to those in the reference spectra were successfully extracted by using this method. This procedure improved mass spectral quality and the ability of the data system to perform successful library searches. The fitted quality parameters showed systematic improvements after the data were subjected to the spectral enhancement procedures. These procedures could help to identify unknowns by separating their spectra from other signals, such as those of background aliphatic hydrocarbons.

Photosynthetic and transpirational responses of red spruce understory trees to light and temperature.

Understory red spruce (Picea rubens Sarg.) trees, between 20 and 50 cm in height and 12 years or more in age, were collected from mid- and high-elevation stands in north-central Vermont and placed in a closed-cuvette system to measure photosynthetic and transpirational responses to photosynthetic photon flux density (PPFD) and temperature. Photosynthesis, dark respiration, transpiration and water-use efficiency of trees from both stands responded to changes in PPFD and temperature in similar ways. Trees from both stands exhibited maximum rates of net photosynthesis at temperatures between 15 and 20 degrees C, and exposure to higher temperatures resulted in reduced rates of photosynthesis and increased rates of respiration. Net photosynthetic rates generally increased with increasing light intensity but began to level off at 250 micro mol m(-2) s(-1). Water-use efficiency was maximal when temperature and PPFD were at 15 degrees C and above 400 micro mol m(-2) s(-1), respectively.

Winter photosynthesis of red spruce from three Vermont seed sources.

We evaluated winter (January through March) carbon assimilation of red spruce (Picea rubens Sarg.) from three Vermont seed sources grown in a common garden in northwestern Vermont. Although CO(2) exchange rates were generally low, net photosynthetic rates increased during two prolonged thaws. Significant correlations between CO(2) exchange rates and multiday air temperature means supported our observations of enhanced gas exchange during extended periods of elevated temperature. Increases in photosynthesis during thaws occurred before observed increases in leaf conductance, indicating that initial changes in photosynthesis were probably not associated with changes in stomatal aperture. Results of correlations between photosynthetic rates and PAR suggested that solar irradiance did not have a strong effect on winter carbon capture. Rates of net photosynthesis differed among seed sources. Trees from the Mt. Mansfield source had the highest average rates of photosynthesis and, at times, rates for individual trees from this source approximated those occurring during the growing season. Because seed sources differed in photosynthetic rates but not in leaf conductance, we conclude that differences in winter photosynthesis among seed sources were primarily attributable to factors other than changes in stomatal aperture.

Characterization of dibromopolychlorodibenzo-p-dioxins and dibromopolychlorodibenzofurans in municipal waste incinerator fly ash using gas chromatography/mass spectrometry.

Several fly ash samples from different countries were analyzed for dibromopolychlorodibenzo-p-dioxins and -dibenzofurans (DBPCDD/Fs) using capillary column gas chromatography/high-resolution mass spectrometry. Concentrations of these compounds ranged from low to high parts-per-trillion (pptr) depending on the location where the samples were collected. The mass spectrometer, operated at greater than 10,000 mass resolution in combination with the high resolving power of capillary column GC, permitted characterization of DBPCDD/Fs in municipal waste incinerator fly ash for the first time. The isomer patterns of tetra- through octa-congener groups of DBPCDD/Fs are remarkably similar regardless of where the fly ash originated, indicating common mechanisms of formation of these compounds in the incinerators.

Bromo- and bromochloro-polynuclear aromatic hydrocarbons, dioxins and dibenzofurans in municipal incinerator fly ash.

A fly ash sample found to contain polychlorinated dioxins and dibenzofurans was analyzed for brominated analytes. Bromochloro-polynuclear aromatic hydrocarbons, dioxins and dibenzofurans, as well as bromo PAH were found in ppt to ppb concentrations. Analytical results were confirmed by high-resolution mass spectrometric accurate mass determinations and by tandem mass spectrometry.

Ion abundance criteria for gas chromatographic/mass spectrometric environmental analysis.

Mass and intensity calibration of gas chromatograph/mass spectrometer (GC/MS) responses is an important quality assurance issue for chemical analysis. Ion abundance calibration with decafluorotriphenylphosphine (DFTPP) was applied in 1975 to standardize quadrupole spectra to resemble the ion abundances that were obtainable from magnetic sector mass spectrometers. Modern quadrupole mass spectrometers provide significantly greater high-mass sensitivity than allowed under the 1975 study. Thus, those recommendations were reevaluated with 2 approaches. First, an interlaboratory study was conducted using 15 different gas chromatography/mass spectrometry (GC/MS) systems. Second, the U.S. Environmental Protection Agency Contract Laboratory Program (EPA-CLP) quality assurance data base was searched and over 6500 DFTPP tune results were plotted and evaluated. Based on these approaches, updated ion abundance criteria recommendations have been developed, which contemporary instruments can meet, and which meet data quality objectives regarding identification and quantitative analysis of analytes.

Effects of helminth infection on the pre-weaning production of ewes and lambs: comparison between safe and contaminated pasture.

Comparison was made of the performances of cross-bred ewes and their lambs on pastures of low helminth infectivity ("safe" pastures) or contaminated pastures and at high or low stocking rates. Ewes grazing the safe, but not the contaminated, pastures were given a single pre-lambing drench. The largest difference in parasite infection between treatments was the level of exposure of sheep to Trichostrongylus spp, which was negligible on the safe pastures. The effects of parasite control on lamb growth were significant only in twins during the last 2 months before weaning. However, 22% of lambs on contaminated plots became soiled in the breech area and 38% were flystruck, compared with 8% and 10% respectively for lambs on the safe pastures. Ewe bodyweight gains were greater at low than at high stocking rate and were not affected by the parasite control treatments; differences in breech soiling and fly strike were similar to those in the lambs. Most importantly the parasite treatment produced a highly significant effect on ewe fleece weight at weaning. Ewes drenched and lambing on the safe pastures produced an extra 0.43 kg of wool, calculated to represent an increase of at least 40% during this period at the low-level of parasitic infection.

Effects of helminth infection on the pre-weaning production of ewes and lambs: evaluation of pre- and post-lambing drenching and provision of safe lambing pasture.

The pre-weaning production of ewes and lambs in spring on pastures grazed during the previous autumn and early winter by either weaner sheep, adult sheep, or cattle was investigated together with estimating the benefits of pre- and post-lambing drenches to ewes. These treatments were compared with one in which parasitism was uncontrolled in ewes lambing on pastures grazed previously by untreated weaner sheep, and another where parasitism was suppressed by 2-weekly drenching of the weaner sheep and also of the ewes and their lambs. Prior grazing by cattle effectively eliminated infection of pastures with intestinal Trichostrongylus and Nematodirus spp, but less so for Ostertagia spp. Worthwhile reductions in contamination were also achieved by grazing by adult sheep compared with grazing by undrenched weaners. Despite differences in the parasitological status of the pastures, there were no indications that pre-weaning growth rates of lambs were affected. However, wool growth in ewes was reduced by 10 to 20% by parasite infection. Wool growth of ewes on pastures grazed by cattle during the pre-experimental period exceeded that on any other treatment, and was significantly greater than that of ewes on pastures grazed by undrenched weaners. There was no production benefit in giving a pre-lambing drench to ewes on plots contaminated by weaners, or in giving the additional post-lambing drench to ewes grazing on plots contaminated by weaners, adult sheep or cattle.