bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole blood impedance aggregometry for the assessment of platelet function in patients with congestive heart failure (EPCOT Trial)
Authors: Serebruany V.L. , McKenzie M.E. , Meister A.F. , Fuzaylov S.Y. , Gurbel P.A. , Atar D. , Gattis W.A. , O'Connor C.M. 
Published: October 2002

AbstractObjectiveData from small studies have shown the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of the whole blood aggregometry (WBA) in a random outpatient CHF population.MethodsBlood samples were obtained for measurement of whole blood aggregation, shear‐induced closure time, platelet contractile force, expression of GP IIb/IIIa, and P‐selectin in 100 consecutive patients with CHF.ResultsSubstantial inter‐individual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were divided by the incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Surprisingly, aspirin use did not affect instrument readings as well. Whole blood aggregometry correlates well with the closure time (r2‐0.587), and with GP IIb/IIIa expression (r2‐0.435). Significant but less strong correlation has been observed for the WBA with platelet P‐selectin expression (r2‐0.295), and no correlation was present for the platelet contractile force measures (r2‐0.030).ConclusionsDespite the fact that patients with heart failure enrolled in the EPCOT trial exhibited marginal, sometimes oppositely directed changes, in their platelet characteristics, whole blood impedance aggregometry is indeed capable to serve as a valuable diagnostic tool, and may be successfully used as an established screening device in this population. Ability of the whole blood aggregometry to predict clinical outcomes, or for the monitoring of anti‐platelet agents in CHF patients, will be evaluated in the ongoing clinical trials.
Clinical depression is common and significantly associated with reduced survival in patients with non‐ischaemic heart failure
Authors: Faris R. , Purcell H. , Henein M.Y. , Coats A.J.S. 
Published: October 2002

AbstractSeveral studies have shown that depression is an important predictor of morbidity and mortality in patients with ischaemic heart failure. We have investigated whether clinically recognised depression is linked to mortality in patients with non‐ischaemic heart failure due to dilated cardiomyopathy (DCM) in the Royal Brompton Hospital (RBH), a tertiary cardiac centre located in London, UK. We retrospectively examined a cohort of 396 consecutive adult patients with DCM who satisfied our inclusion and exclusion criteria identified from an echocardiographic database and the hospital medical records. Mean age was 53±15 years. In all, 83 patients (21%) were clinically depressed, the majority of which (60%) were taking antidepressant therapy. After a follow‐up period of 48 months, 83 (21%) patients died, 15 (4%) underwent cardiac transplantation and 130 (33%) were readmitted; 29 (35%) of the deaths and 40 (31%) of the readmissions were among clinically depressed patients. After 5 years, clinically depressed patients had significantly higher mortality and readmission rates than non‐depressed; 36 vs. 16% (hazards ratio for death, 3.0; 95% CI, 1.4–6.4;P‐0.004), and 87 vs. 74% (hazards ratio for readmission, 0.25; 95% CI, 0.07–0.90;P‐0.03), respectively. The risk of depression was greatly increased in the presence of other recognised adverse clinical variables at baseline. Depression increases the risk of death and readmission in patients with heart failure secondary to non‐ischaemic DCM. The risk associated with depression appears to be greatest among patients with milder disease, those with a shorter duration of symptoms and those demonstrating a lower systolic or diastolic blood pressure, renal impairment, or a restrictive left ventricular physiology on echocardiography. Interventions targeted at reducing depression warrant further study as a possible way to improve quality of life and/or outcome in patients with heart failure.
Between-days reliability of electromyographic measures of paraspinal muscle fatigue at 40, 50 and 60% levels of maximal voluntary contractile force
Authors: Arnall Frances A , Koumantakis George A , Oldham Jacqueline A , Cooper Robert G 
Published: October 2002

Objective: To ascertain which percentage of maximal voluntary contractile force of the paraspinal muscles, when tested in a functional position, is most reliable for assessing electromyographic (EMG) fatigue changes. Subjects: Ten healthy volunteers with no history of low back pain (six males). Main outcome measures: The surface EMG signal during 60-second isometric contractions of the paraspinal muscles at 40, 50 and 60% levels of maximal voluntary contractile force was captured and analysed. Each contraction level was assessed on two occasions, at least three days apart. The initial median frequency, the decline in median frequency slope and the increase in root mean square values were assessed for between-days reliability, using intraclass correlation coefficients (ICCs) and standard errors of measurements (SEM). Normalized median frequency and root mean square values were also assessed. Results: At 40% of maximal voluntary contraction, little or no EMG fatigue changes occurred in any of the observed parameters. At 50% maximal voluntary contraction the initial mean frequency and root mean square changes proved highly reliable, with ICCs ranging from 0.74 to 0.86 and 0.75 to 1.00 respectively. Normalizing the root mean square data reduced the reliability, but this was still acceptable with ICCs 0.70–0.83. The median frequency decline slope proved less reliable with ICCs 0.24–0.74 for raw and 0.26–0.77 for normalized data. At 60% maximal voluntary contraction the initial mean frequency proved as reliable as initial median frequency at 50% with ICCs 0.70–0.89. The raw and normalized root mean squares (ICCs 0.43–0.89 and 0.30–0.87 respectively) and raw and normalized median frequency (ICCs 0.27–0.51 and 0.24–0.53 respectively) changes were less reliable than at 50% MVC. Overall, the reliability is better at the L4/5 than at the L2/3 level. Conclusion: Outcome measures taken at 50% maximal voluntary contraction are the most reliable in functional testing the paraspinal muscles of healthy volunteers. With initial median frequency and root mean square values being more reliable parameters than median frequency decline. At the L4/5 level, however, all parameters were acceptably reliable at 50% of maximum effort. However the between-subject variability of the median frequency decline and root mean square incline slopes suggest that these parameters are not yet fully suitable for monitoring fatigue changes during prolonged isometric contraction.
Water structure theory and some implications for drug design
Authors: Plumridge T H , Waigh R D 
Published: October 2002

Abstract
The development of theories of water structure has been hindered in the past by the difficulty of experimental measurement. Both measurement and computer modelling studies have now reached the stage where theoretical treatments of water structure are converging to a broadly acceptable model. In current understanding, water is a mixture of randomly hydrogen-bonded molecules and larger structures comprised of tetrahedral oxygen centres which, when hydrogen-bonded to each other, lead to five-membered and other rings which can aggregate to form three-dimensional structures. Evidence is taken from studies of the ices, from clathrates and other solid solutions, as well as from liquid solutions, that certain motifs occur very frequently and have relatively high stability, such as the (H2O)20 cavity-forming structure known from studies on clathrates. The implications of recent models of water structure for an understanding of biological events, including the interactions of drugs with receptors, are profound. It is becoming clear that modelling of aqueous solutions of any molecule must consider the explicit interactions with water molecules, which should not be regarded as a continuum: water itself is not a continuum. Solute molecules which possess hydrogen-bonding groups will provoke the formation of further hydrogen-bonding chains of water molecules: if these can form rings, such rings will tend to persist longer than chains, giving the solute a secondary identity of associated water which may play a role in molecular recognition. Solutes that do not have hydrogen-bonding capability, or regions of solutes which are non-polar, may also produce partial cage-like water structures that are characteristic of the solute.
The classification of many solutes as structure makers or structure breakers has relevance to the interactions between ligands and large biomolecules such as proteins. While it is generally accepted that sulfate and urea, respectively structure maker and breaker, may alter protein conformation through effects on water, it has not been recognised that bioactive ligands, which also change the conformation of proteins, may do so by a related, but more selective, mechanism. Very early studies of cell contents suggested that the associated water might be different from bulk water, a concept that lost support in the mid-20th century. Current theories of water structure may invite a reappraisal of this position, given the observation that structuring may extend for many molecular diameters from an ordered surface.
A novel insulin formulation can keep providing steady levels of insulin for much longer periods in-vivo
Authors: Takenaga Mitsuko , Yamaguchi Yoko , Kitagawa Aki , Ogawa Yasuaki , Mizushima Yutaka , Igarashi Rie 
Published: October 2002

Abstract
We have recently succeeded in preparing insulin-loaded microcapsules that release the insulin in a strictly controlled manner with little initial rapid release in-vitro or in-vivo. We show here the superiority of the best formulation prepared with co-poly(d,l-lactic/glycolic) acids (PLGA) (mean MW 5800, L/G ratio 50:50) with a main diameter of 15 ˜ 30 μm in-vivo. When 3.2% insulin-loaded PLGA microcapsules were subcutaneously given as a single dose to streptozotocin-induced hyperglycaemic rats (250 U kg−1), plasma insulin levels gradually increased and constant levels (30.3–94.1 μL−1) were sustained. Rats receiving the formulation once a week showed not only steady plasma insulin levels, but also gained weight at a similar speed to normal rats. Meanwhile, daily treatment with Humulin U (25 U kg−1) caused a transient high insulin level (2723.9 μU mL−1 at 1 h) in plasma, but the body weight of the rats was little changed. A pharmacological study in female Cynomolgus monkeys also revealed that the microcapsular formulation provided a flat release of insulin for longer periods and showed no immunogenic activity. In the near future, therefore, this insulin formulation could become very beneficial as a provider of basal insulin levels for insulin-dependent diabetic patients.
Polymer-coated microparticles for the sustained release of nitrofurantoin
Authors: Liu Jita , Chan Sui Y , Ho Paul C 
Published: October 2002

Abstract
Suspensions of nitrofurantoin (NTF) microparticles for controlled release were investigated in this study. The microparticles were enteric coated with various combinations of the two polymers, cellulose acetate phthalate/cellulose acetate butyrate (CAP/CAB) by a modified solvent evaporation method. Ratios of NTF to the two polymers (NTF/CAP/CAB) ranged from 1.0:1.6:0.4, 1.0:1.0:1.0, 1.0: 0.4:1.6 to 1.0:0.0:2.0. The encapsulation efficiency, percentage yield, determined by comparing the final mass of the microparticles with the initial mass of the ingredients used, distribution of particle size and the in-vitro dissolution profiles of the microparticles were determined. Based on light photographs for the evaluation of the microparticle morphology, the drug crystals appeared to be encapsulated sufficiently by the enteric polymers. In our study, the microparticles enteric coated with CAP/CAB in the ratio of 0.4:1.6 displayed the most satisfactory in-vitro release profile (reduced release in the simulated gastric fluid and sustained release in the simulated intestinal fluid). Thus, microparticles with NTF/CAP/CAB in the ratio of 1.0:0.4:1.6 were formulated into a suspension for further bioavailability and ulcerogenicity studies in Sprague–Dawley rats, with the suspension of NTF crystals as a control. The bioavailability study was carried out in eight rats fed with either the free NTF or the corresponding microparticles in a cross-over design. The ulcerogenicity study was carried out in three groups of six rats each: one group received no drug treatment; the control group was treated with free NTF; and the third group was treated with enteric-coated NTF microparticles. The bioavailability of NTF from the microparticles was comparable with the control. More importantly, there was notably less ulceration of the gastric mucosa observed after dosing with the microparticle suspension compared with that after the administration of the control suspension.
Determinant of the distribution volume at steady state for novel quinolone pazufloxacin in rats
Authors: Hayakawa Hiroyoshi , Takagi Kyoko , Takano Yoko Fukushima , Kawamura Yasuhito , Tsuji Akira 
Published: October 2002

Abstract
The distribution properties of the novel quinolone pazufloxacin (PZFX) in rats were compared with those of sparfloxacin (SPFX) and ofloxacin (OFLX). Following intravenous administration of these quinolones to rats, the distribution volume at steady state (Vdss) of PZFX was found to be 0.945 L kg−1, whereas for OFLX and SPFX it was 1.83 and 3.42 L kg1, respectively. In order to understand this difference in Vdss, first the contribution of each tissue to the Vdss using pharmacokinetic parameters was estimated and it was found that the type of tissue contributing the most was muscle. Subsequently, we determined the extent of tissue binding and uptake clearance (CLuptake) in the muscle. The ratio of unbound fraction of plasma to unbound fraction of muscle was almost equal for all quinolones tested, with values of 1.60, 1.52 and 1.32 for PZFX, OFLX and SPFX, respectively. In contrast, the tissue CLuptake of PZFX in the muscle (0.012 mL min−1 g−1) was significantly lower than that of OFLX and SPFX (0.118 and 0.195 mL min−1 g−1, respectively). These results suggest that the low Vdss value for PZFX can be attributed to the low CLuptake in the muscle.
Prediction of the volume of distribution of a drug: which tissue-plasma partition coefficients are needed?
Authors: Björkman Sven 
Published: October 2002

Abstract
The aim of this study was to identify the tissue-plasma partition coefficients (Kp) needed for an initial prediction of the volume of distribution at steady state (Vdss) of a drug in humans. Values of Kp were collected from the literature. Only Kp values plausibly representing true steady state distribution were accepted, and data had to be available for muscle, fat, skin and at least five other organs. The apparent volume of distribution of a drug in an organ/tissue (Vapp) was calculated as Kp multiplied by the volume of the organ/tissue, and the Vdss as the sum of all available Vapp values. The percentage contribution of each Vapp to the Vdss was estimated. In addition, linear regressions were calculated between Kp values of all drugs in a specific organ/tissue and Kp in muscle or fat. Finally, the Vdss was re-calculated using (for basic drugs) the Kp in fat to calculate Vapp in fat and lungs and the Kp in muscle for the Vapp of all other organs/tissues. The two sets of estimates of Vdss were compared by linear regression. The same calculations were performed for acidic drugs, except that muscle Kp was used also for the lungs. Distribution to fat and muscle accounted for 84% (61–91%) (median and range) of the total estimated Vdss of the basic drugs (n = 17). The regressions between Kp in organs/tissues and muscle Kp were statistically significant except in the case of liver. For acidic drugs (n = 18), distribution to fat and muscle accounted for 65% (42–92%) of Vdss, and the regressions of Kp were significant for all organs/tissues except kidney and bone. For both types of drugs, correlations between organ/tissue Kp values and Kp in fat were generally worse. There were excellent linear correlations between Vdss calculated by means of only two Kp values and the originally calculated Vdss (r2 ≥ 0.99 for both basic and acidic drugs; slopes were not significantly different from unity). Thus, initial estimation of the Vdss of a new drug can normally be based on only two Kp values, those of muscle and fat. The muscle Kp can be used to represent all lean tissues, including the residual “carcass”, with the exception that fat Kp can be used for distribution of basic drugs to lungs.
The quantification of citral in lemongrass and lemon oils by near-infrared spectroscopy
Authors: Wilson Nicola D , Ivanova Maria S , Watt Robert A , Moffat Anthony C 
Published: October 2002

Abstract
Previous work has demonstrated the capability of near-infrared (NIR) spectroscopy to determine the cineole content (not less than 70% w/w) of eucalyptus oil with an accuracy comparable with that of the British Pharmacopoeia (BP) assay method. The aim of the present study was to determine if the same method was capable of quantifying other chemical constituents at similar levels in essential oils and also to ascertain if NIR spectroscopy can accurately quantify compounds present at much lower levels in essential oils. Lemongrass oil contains citral at concentrations of approximately 65–85% w/w, and lemon oil contains citral at a concentration of approximately 2–5% w/w. A total of 26 samples of pure lemongrass oil and 35 samples of pure lemon oil (both including samples that were “spiked” with citral to increase the calibration range) were scanned on the FOSS NIRSystems 6500 Rapid Content Sampler using a reflectance vessel as sample presentation method. The reference method for both types of oil was the BP monograph titration assay for the citral content of lemon oil and calibrations were constructed using these reference data. For the lemongrass oils, the mean accuracy was found to be 1.00% or less and the mean bias was 0.09% or less. For the lemon oils, the mean accuracy was found to be 4.28% or less and the mean bias was −0.71% or less. The NIR method developed was rapid, simple and non-destructive and may prove beneficial for the accurate determination of the citral content of lemongrass oils and for the approximate citral content of lemon oils.
The influence of lithium on the antidiuretic effect of desmopressin
Authors: Callréus Torbjörn , Holmquist Ing-Britt , Lundin Stefan , Höglund Peter 
Published: October 2002

Abstract
The objective of this study was to investigate the graded influence from lithium on the antidiuretic effects of desmopressin. Eight healthy male subjects participated in this open, randomised cross-over study with two periods comprising 6 days each. For each subject, one of the study days (6th day) was preceded by a period of lithium treatment. On the study days the subjects were orally water loaded to achieve a state of overhydration with a high urine flow rate. When a steady-state diuresis was achieved after approximately 2 h, 0.396 μg of desmopressin was administered intravenously as a bolus injection. An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fitted to the urine osmolarity data. The effects of the independent variables, Uflow (baseline) (baseline urine flow rate), R0 (baseline osmolarity) and serum lithium concentration, on IC50 (concentration producing 50% of the maximum inhibition) could be expressed by multiple linear regression. In conclusion, we found that an indirect-response model can be a useful tool in investigating and describing the pharmacodynamic interaction between drugs, in this particular case, between lithium and desmopressin.
Simultaneous detection of monohydroxybenzo[a]pyrene positional isomers by reversed‐phase liquid chromatography coupled to electrospray ionization mass spectrometry
Authors: Sasaki Hideki , Yonekubo Jun , Kanai Michiko , Toriba Akira , Kizu Ryoichi , Hayakawa Kazuichi 
Published: October 2002

AbstractA liquid chromatographic (LC) method has been developed for the separation of 11 monohydroxybenzo[a]pyrenes (OH BaPs) positional isomers, and for their detection using electrospray ionization mass spectrometry (ESI‐MS). All OH BaPs isomers were separated on an octadecylsilyl (C18)‐bonded amorphous organosilica column utilizing gradient elution with acetonitrile–water and triethylamine (TEA) at pH 11.0 and determined by MS, except 2‐ and 8‐OH BaPs which were coeluted. The lower detection limits were in the range from 1.6 µg/L for 12‐OH BaP to 12 µg/L for 5‐OH BaP without any sample enrichment. The relative standard deviations of area response were in the range from 1.8% (9‐OH BaP) to 4.9% (12‐OH BaP) except for 9.4% (7‐OH BaP). The developed method was successfully applied to incubation mixtures of BaP and CYP1A1/epoxide hydrolase. This method identified 1‐, 3‐ and 9‐OH BaPs as the major metabolites, and 2‐ (and/or 8‐) and 12‐OH BaPs as the minor metabolites in the incubation mixture. Copyright © 2002 John Wiley & Sons, Ltd.
Inner arm dynein 1 is essential for Ca++‐dependent ciliary reversals in Tetrahymena thermophila
Authors: Hennessey Todd M. , Kim Daniel Y. , Oberski Danial J. , Hard Robert , Rankin Scott A. , Pennock David G. 
Published: October 2002

AbstractCilia in many organisms undergo a phenomenon called ciliary reversal during which the cilia reverse the beat direction, and the cell swims backwards. Ciliary reversal is typically caused by a depolarizing stimulus that ultimately leads to a rise in intraciliary Ca++ levels. It is this increase in intraciliary Ca++ that triggers ciliary reversal. However, the mechanism by which an increase in intraciliary Ca++ causes ciliary reversal is not known. We have previously mutated the DYH6 gene of Tetrahymena thermophila by targeted gene knockout and shown that the knockout mutants (KO6 mutants) are missing inner arm dynein 1 (I1). In this study, we show that KO6 mutants do not swim backward in response to depolarizing stimuli. In addition to being unable to swim backwards, KO6 mutants swim forward at approximately one half the velocity of wild‐type cells. However, the ciliary beat frequency in KO6 mutants is indistinguishable from that of wild‐type cells, suggesting that the slow forward swimming of KO6 mutants is caused by an altered waveform rather than an altered beat frequency. Live KO6 cells are also able to increase and decrease their swim speeds in response to stimuli, suggesting that some aspects of their swim speed regulation mechanisms are intact. Detergent‐permeabilized KO6 mutants fail to undergo Ca++‐dependent ciliary reversals and do not show Ca++‐dependent changes in swim speed after MgATP reactivation, indicating that the axonemal machinery required for these responses is insensitive to Ca++ in KO6 mutants. We conclude that Tetrahymena inner arm dynein 1 is not only an essential part of the Ca++‐dependent ciliary reversal mechanism but it also may contribute to Ca++‐dependent changes in swim speed and to the formation of normal waveform during forward swimming. Cell Motil. Cytoskeleton 53:281–288, 2002. © 2002 Wiley‐Liss, Inc.