bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of trans-antisense transcripts in Arabidopsis thaliana
Authors: Wang Huan , Chua Nam-Hai , Wang Xiu-Jie 
Published: October 2006

Abstract
Background
Natural antisense transcripts (NATs) are coding or non-coding RNAs with sequence complementarity to other transcripts (sense transcripts). These RNAs could potentially regulate the expression of their sense partner(s) at either the transcriptional or post-transcriptional level. Experimental and computational methods have demonstrated the widespread occurrence of NATs in eukaryotes. However, most previous studies only focused on cis-NATs with little attention being paid to NATs that originate in trans.

Results
We have performed a genome-wide screen of trans-NATs in Arabidopsis thaliana and identified 1,320 putative trans-NAT pairs. An RNA annealing program predicted that most trans-NATs could form extended double-stranded RNA duplexes with their sense partners. Among trans-NATs with available expression data, more than 85% were found in the same tissue as their sense partners; of these, 67% were found in the same cell as their sense partners at comparable expression levels. For about 60% of Arabidopsis trans-NATs, orthologs of at least one transcript of the pair also had trans-NAT partners in either Populus trichocarpa or Oryza sativa. The observation that 430 transcripts had both putative cis- and trans-NATs implicates multiple regulations by antisense transcripts. The potential roles of trans-NATs in inducing post-transcriptional gene silencing and in regulating alternative splicing were also examined.

Conclusion
The Arabidopsis transcriptome contains a fairly large number of trans-NATs, whose possible functions include silencing of the corresponding sense transcripts or altering their splicing patterns. The interlaced relationships observed in some cis- and trans-NAT pairs suggest that antisense transcripts could be involved in complex regulatory networks in eukaryotes.
The Effect of Latent Hardening on the Texture of 3004 Aluminum Deformed in Plane Strain, Predicted by an Explicit Dynamic Finite Element Analysis
Authors: Young MJ , Choi SK , Thomson PF 
Published: October 2006

Abstract
Simulating plane strain compression of polycrystalline 3004 aluminum, representing a metal of high stacking fault energy (sfe), to 60% reduction by a finite element model permits prediction of the observed texture, in which the copper, S, and brass components co-exist (predicted by neither the Taylor nor the Sachs models). Modeling the rate of hardening on individual slip planes and latent hardening introduces additional shear strains and increases the volume fraction of the brass component, showing how the brass texture may develop in metals of high sfe, in the absence of twinning and shear banding as suggested by Leffers and Pedersen and by Engler.
Schubert's Sonata Forms and the Poetics of the Lyric
Authors: MAK SU YIN 
Published: October 2006

ABSTRACT
Although recent scholarship has witnessed a welcome disavowal of the view that Schubert's formal and tonal designs in sonata form compositions bespeak the song composer's inability to master large-scale instrumental genres, it remains a commonplace to characterize Schubert's unorthodox practice as “lyrical.” Yet the historical, theoretical, and aesthetic bases of this lyricism have received little critical attention. A systematic and historically grounded approach to the notion of lyrical form in Schubert may be established by appealing to the rhetorical distinction between hypotaxis and parataxis, which pervaded late 18th-century discussions of both music and language. In particular, parataxis, a style that deliberately omits syntactical connections and relies instead on juxtaposition and parallelism, offers a suggestive technical link between Schubert's instrumental practice and the discursive techniques of contemporaneous lyric poetry. There are also aesthetic connections between idealist views of the lyric and the composer's own artistic beliefs, as confirmed by biographical documents. Schubert's approach to form was as much informed by these literary sensibilities as by the Classical compositional tradition. Like poets for whom the lyric served both as an Arcadian ideal of song and as an alternative to the prosaic realities of the present, Schubert evoked the lyric within the context of the sonata as a means of reunifying the dissociated sensibility of the Enlightenment. In so doing, he secured a place for the poetic imagination in instrumental music.
Carbon‐Nanotube‐Based Hybrid Materials: Nanopeapods
Authors: Kitaura Ryo , Shinohara Hisanori 
Published: October 2006

AbstractThis review article focuses on the structures and properties of novel hybrid nanocarbon materials, which are created by incorporating atoms and molecules into the hollow spaces of carbon nanotubes (CNTs); thus they are called nanopeapods. After dealing with synthesis procedures, we discuss the structures and electronic properties of the hybrid materials based on high‐resolution transmission electron microscopy (HRTEM), electron energy‐loss spectroscopy (EELS), X‐ray and electron diffraction, scanning tunneling microscopy (STM), and field‐effect transistor transport measurements. Utilization of the low‐dimensional nanosized spaces of CNTs to produce novel low‐dimensional nanocluster, nanowire, and nanotube materials is also discussed.
Plasma levels of chlorodesmethyldiazepam in humans
Authors: Bo L. Dal , Marcucci F. , Mussini E. , Perbellini D. , Castellani A. , Fresia P. 
Published: October 2006

AbstractChlorodesmethyldiazepam (I) concentrations were followed for 72 h in the plasma of four volunteers given 2 mg of the drug orally. The drug appears to be well absorbed, reaching peak plasma levels of 20–30 ng ml−1 1–2 h after administration; 72 h after administration, plasma concentrations are still measurable (5 ng ml−1).The analytical method involved a single extraction of I from the plasma into benzene followed by centrifugation, evaporation, and gas‐chromatographic analysis of the samples.
The effect of displacement from protein binding on serum and tissue fluid levels of cephazolin
Authors: Polacek I. , Mühlbauer H. 
Published: October 2006

AbstractDisplacement of cephazolin, a highly protein‐bound β‐lactam antibiotic, by sulpha‐phenazole was studied in vitro and in vivo. In vitro, the sulphonamide was effective in displacing the antibiotic from its binding sites at the concentration 100–1000 μmol I−1. In vivo, both the serum and the tissue fluid concentration of free cephazolin increased significantly in rats concomitantly treated with sulphaphenazole.
Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects
Authors: Taylor T. , Chasseaud L. F. , Doyle E. , Darragh A. , O'Kelly D. A. , Fitzgerald D. 
Published: October 2006

AbstractPlasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5·0 mg h−1 for 150 min and after single equal oral doses of 12·5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady‐state plasma levels were 258 ng ml−1 and 514 ng ml−1 in the two subjects respectively. The half‐life of elimination of isosorbide dinitrate after termination of the infusion was 9–10 min. After oral doses, peak plasma levels of 26·6 ng ml−1 and 12·7 ng ml−1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half‐life of drug after the oral doses was much longer than the elimination half‐life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one‐compartment open model.The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0·32 1 min−1 and 0·161 min−1 were unexpectedly low for a drug of reported high liver extraction ratio.
A propranolol radioimmunoassay and its use in the study of its pharmaco‐kinetics following low doses
Authors: Mould G. P. , Clough J. , Morris B. A. , Stout G. , Marks V. 
Published: October 2006

AbstractA radioimmunoassay has been developed for propranolol with a sensitivity of 2.37nmol l−1 in unextracted plasma using a 50 μl sample. Plasma concentration measurements were made on samples from volunteers for up to 8 h after they had been given 5, 10, or 40 mg of propranolol by mouth. Analysis of the results showed that mean elimination half‐lives and total body clearances were similar following each of the doses and that the area under the curve was proportional to the dose. Steady‐state propranolol concentrations in 17 patients on regular propranolol treatment were linearly related to the dose over the range 20.640 mg d −1; the regression line extrapolated to the origin. These data indicate non‐saturable kinetics for the hepatic metabolism of propranolol within the dose ranges investigated and lead us to believe that there is no ‘oral‐threshold’ dose for propranolol. The radioimmunoassay may be useful in clinical practice for monitoring plasma propranolol concentrations and for detecting patient compliance.
Concentrations of N‐descyclopropyl‐methylprazepam in whole‐blood, plasma, and milk after administration of prazepam to humans
Authors: Brodie R. R. , Chasseaud L. F. , Taylor T. 
Published: October 2006

AbstractAfter oral doses of 30 mg of prazepam to humans, N‐descyclopropylmethylprazepam (desalkylprazepam, N‐desmethyldiazepam) is the only major drug‐related compound in plasma. Neither the parent drug, nor its major urinary metabolites were detected in plasma. The overall concentration‐time profile of desalkylprazepamDesalkylprazepam is used as a simplified name for N‐descyclopropylmethylprazepam.
in the plasma of females was lower than, and significantly different (p< 0.001) from that in the plasma of males. However, the mean peak desalkylprazepam concentrations in the plasma of females (265 ng ml−1 ±60 S.D.) were not significantly different (p >0.05) from those in males (342ngml−1 ±60 S.D.). Concentrations declined in the plasma of either sex with similar half‐lives (mean 60 h, range 37–93 h). Apparent plasma desalkylprazepam clearances were also similar (mean 1.09 1 h−1, range 0.74–1.84 1 h−1).At 12 h after the last of multiple doses of prazepam (60 mg d−1 for 3 days) to lactating women, mean plasma concentrations of desalkylprazepam were 823 ng ml−1 ±200 S.D. and declined with a mean half‐life of about 60 h over the time‐course studied. There was only slight uptake of desalkylprazepam into blood cells; plasma : whole blood concentration ratios were constant at about 1.6. Concentrations of desalkylprazepam in milk were low at about 10 percent of the corresponding plasma levels (e.g. 86 ng ml−1 ±37 S.D. at 12 h). The data suggest that, expressed on a mg kg−1 basis, exposed neonates could receive about 4 per cent of the maternal dose of prazepam as desalkylprazepam.
The effect of antacid, metoclopramide, and propantheline on the bioavailability of metoprolol and atenolol
Authors: Regardh Carl G. , Lundborg Per , Persson Bengt A. 
Published: October 2006

AbstractConcomitant administration of antacid increased the maximum concentration (Cpmax) and the area under the plasma concentration‐time curve (AUC) of 100 mg oral dose of metoprolol by 25 per cent (p< 0.05) and 11 per cent (p < 0.1) respectively. For atenolol the opposite effect was observed and Cpmax and AUC were decreased by 37 and 33 per cent respectively (p< 0.02). In both cases the antacid did not affect the time‐course of the drug in the plasma. Pretreatment with metoclopramide did not affect the time‐course of atenolol in the plasma or its bioavailability. Propantheline prolonged the absorption phase of atenolol and the time of peaking (tmax) was shifted from 2.1 to 4.5 h. Cpmax of atenolol was essentially unchanged by propantheline pretreatment while the AUC was increased by 36 per cent. It is concluded that the negative effect of the antacid on the bioavailability of atenolol is caused by a reduction in the in vivo dissolution rate due to increased gastric pH. The positive effect of propantheline might be due either to more efficient absorption of atenolol in the upper part of the intestine or more extensive dissolution of the drug as a result of prolonged contact with gastric juice or a combination of these factors.
Pharmacokinetic evaluation of noreximide in rats
Authors: Koch Heinrich P. , Pischek Gertrude , Holzbecher Margarete , Ritschel Wolfgang A. 
Published: October 2006

AbstractThe pharmacokinetics of noreximide in the rat after i.v., p.o., and i.p. administration was studied. The biologic half‐life of approximately 8 h was found almost the same for all three routes. Upon p.o. administration the fraction of drug absorbed is 85 per cent, and the peak concentration in the blood is reached within approximately 4.5 h. Additional pharmaco‐kinetic parameters are listed.
Plasma propranolol concentrations in rats with adjuvant‐induced arthritis
Authors: Bishop Hilary , Schneider R. E. , Welling P. G. 
Published: October 2006

AbstractPrevious work has shown that after a single oral dose, plasma propranolol concentrations in patients with active inflammatory disease are significantly higher than those in healthy subjects.After oral administration of propranolol (2 mg) to arthritic rats, the area under the mean drug concentration‐time curve in plasma was approximately 10 times greater than that in control animals. After intravenous administration (0.25 mg) the area in arthritic rats was approximately doubled compared with that in controls.The mechanisms causing these changes are not known, but it is probable that increased drug binding to an acute phase reactant in plasma, together with decreased first‐pass hepatic clearance in arthritic rats after oral dosing, are involved.
Evidence for route dependent biotransformation of cyclobenzaprine hydrochloride
Authors: Till Alice E. , Constanzer Marvin L. , Demetriades Joan , Irvin John D. , Lee Robyn B. , Ferguson Roger K. 
Published: October 2006

AbstractCyclobenzaprine hydrochloride was administered to healthy volunteers as a 10mg oral tablet, 10mg and 20mg intramuscular injections, and a 10mg intravenous injection. Urinary excretion and plasma level data for cyclobenzaprine together provide evidence for route dependent biotransformation. Urinary excretion of total cyclobenzaprine (unchanged plus the glucuronide conjugate) was greater for the oral treatment than for the parenteral treatments (i.m. and i.v.). Area under the plasma concentration‐time curve for unchanged cyclobenzaprine, however, was less for the oral treatment than for the parenteral treatments. Based on area calculations, the bioavailability of the 10 mg oral tablet, 10 mg i.m. and 20 mg i.m. injection was 0.33, 0.76, and 0.56, respectively, when compared to the 10mg i.v. injection of cyclobenzaprine hydrochloride. The four treatments were well tolerated and no clinically adverse effects were observed.
The pharmacokinetics and metabolism of 14C‐carprofen in man
Authors: Ray John E. , Wade Denis N. 
Published: October 2006

AbstractThree healthy male subjects received single 100mg oral doses of carprofen containing 20 μCi of 14C‐carprofen. Venous blood samples were drawn during the first 48 h after the dose and urine and feces were collected for 120h. Concentrations of carprofen and its metabolites in body fluids were determined by TLC and mass spectral analysis. After a lag time of 0.3±0.41h (mean ±S.D.), carprofen was absorbed rapidly and peak concentrations in the plasma were reached in 2.7 ± 1.3 h. The 14C plasma concentrations declined in a biphasic fashion. The mean half‐lives of the initial (α) and terminal (β) phases were 1.1 h and 20.6 ± 6.1 h, respectively. Biotransformation to a glucuronide metabolite appeared to be the major mechanism of carprofen clearance. In 48 h 74.0 per cent of administered radioactivity was recovered in urine and 14.1 per cent was recovered in feces. A glucuronide of carprofen comprised 85.0 per cent of the radiolabelled compounds in urine. The remaining radioactivity was comprised of parent drug (12.0 per cent) and un unidentified acid‐labile conjugate of the parent drug (3.0 per cent). This pattern of metabolism and excretion is different from that in the dog and rat and may explain species differences in drug activity and toxicity.
Comparison of gentamicin and tobramycin nephrotoxicity in patients receiving individualized‐pharmacokinetic dosing regimens
Authors: Pancorbo Salvador , Compty Christina , Heissler Joseph 
Published: October 2006

AbstractThe incidence of nephrotoxicity has been studied in 175 patients who received either gentamicin or tobramycin. All patients received individualized dosing regimens of the drugs based on pharmacokinetic parameters measured after the initial dose. Subsequent doses were calculated from the pharmacokinetic data to produce peak aminoglycoside levels of between 6 and 8 μg ml−1 and trough levels that were below 2 μg ml−1. Renal toxicity was defined as a 30 per cent or greater increase in the serum creatinine level above the baseline value. Five of the 125 patients (4 per cent) who received gentamicin, and 1 of the 39 patients (2.6 per cent) who received tobramycin developed signs of nephrotoxicity. This difference was not statistically significant.
The assessment of fractional drug removal by extracorporeal dialysis
Authors: Lee Ching‐San C. 
Published: October 2006

AbstractIt is generally concurred that the effectiveness of extracorporeal dialysis is best evaluated by fractional drug removal, i.e. the proportion of body burden of drug removed during the period of dialysis treatment. Two equations reported in the literature and five equations proposed in this article are examined for their validity in the assessment of fractional drug removal. Potential limitations and applicable conditions of these equations are discussed and compared. Calculations of fractional drug removal are demonstrated using both simulated and experimental data of ethambutol. Depending on the available kinetic measurements during dialysis and post dialysis, one may apply each equation separately or in conjunction with others to the calculation of fractional drug removal.
Pharmacokinetics of valproic acid and metabolites in mouse plasma and brain following constant‐rate application of the drug and its unsaturated metabolite with an osmotic delivery system
Authors: Nau Heinz , Zierer Rainer 
Published: October 2006

AbstractHuman therapeutic valproic acid (VPA) levels could be maintained in the mouse for a period of 1 week by constant rate application via subcutaneously implanted osmotic minipumps. Also, the concentrations of VPA metabolites observed in mouse plasma were similar to those seen in human plasma. The drug application could be prolonged by replacing exhausted pumps with freshly‐filled devices. Removal of the implanted pumps and measurement of the decay of the drug levels revealed that the half‐life of the main plasma metabolite 2‐en(2‐propyl‐2‐pentenoic acid) exceeded that of VPA. This result was confirmed by constant‐rate application of this metabolite; the plasma clearance of 2‐en (as calculated from the steady‐state levels observed) was found to be lower than that of VPA. Brain levels of VPA and 2‐en during steady‐state were 3–10 per cent of corresponding plasma levels. The blood‐brain kinetics of 2‐en following administration of VPA were similar to those observed following application of 2‐en itself. VPA was cleared faster from the brain than from the plasma, while 2‐en was more persistent in the brain than in the plasma. Our results indicate that controlled, constant‐rate application of drugs such as VPA, via implantable osmotic minipumps, may be a valuable procedure for a number of pharmacological and toxicological studies, particularly where persistent drug levels must be maintained for extended time periods.
Pharmacokinetic evaluation of the blood‐to‐lymph transfer of cyclosporin a in rats
Authors: Ueda Clarence T. , Lemaire Michel , Misslin Pierrette 
Published: October 2006

AbstractThe blood‐to‐lymph transfer kinetics of cyclosporin A (CyA) were investigated in thoracic duct cannulated rats after a 3mg kg−1 i.v. bolus injection of tritium‐labelled drug. Blood CyA concentrations declined bi‐exponentially with a terminal half‐life of 13·1 ± 1·8 h. The appearance rate of CyA in the lymph was also bi‐phasic, initially rising and then declining in parallel with the concentrations of CyA in the blood. A pharmacokinetic model describing the blood‐to‐lymph transfer kinetics of CyA is presented. From the slopes of graphs relating the appearance rate of CyA in the lymph to the corresponding midpoint blood drug concentration, the estimated blood‐to‐lymph clearance rate of CyA (ClL)b was 0·262·0·132 mlh−1 (ClL)b was positively correlated with the average lymph flow rate (Q̄L) but was significantly less than Q̄L. On the other hand, the plasma‐to‐lymph clearance rate of CyA (ClL)P of 0·393 ± 0·198 mlh−1 was positively correlated and similar to Q̄L. Lymph concentrations of CyA were approximately 40–60 per cent of the corresponding blood concentrations. The results of this investigation showed the existence of an intervening compartment between the blood and lymph fluids which would be consistent with the presence of lymph nodes. It was shown that the blood‐to‐lymph transfer of CyA was dependent on the flow rate of the lymph and that CyA appeared to be cleared from the plasma (or serum) fraction of the blood.
Pharmacokinetic studies with atenolol in the dog
Authors: McAinsh James , Holmes Brian F. 
Published: October 2006

AbstractThe pharmacokinetics of the cardioselective β‐adrenoreceptor blocking agent atenolol have been determined following intravenous and oral dosing to the dog. After intravenous administration at 200 mg the blood levels of parent drug were found to decay tri‐exponentially with a final elimination phase half‐life of about 4–5 h. The volume of distribution for the central compartment was 40 per cent body weight and the whole body volume of distribution was 160 per cent body weight. The percentage urinary recovery of parent drug was 83 per cent.Following oral dosing at 400 mg (as a solution and as a clinical trial tablet) the percentage urinary recovery was 65 per cent and the half‐life extended slightly to between 5 and 6h. The peak blood levels were however very similar for the two formulations (17 and 15μg/ml for the solution and tablet respectively) and occurred at the same time (l–2h after dosing). The total areas under the blood concentration time curves were similar and the values (100 and 104ugml−1h respectively) agreed well with that anticipated on the basis of the intravenous data. It was concluded that the two formulations were bioequivalent and that following oral dosing atenolol was almost completely absorbed with little metabolism or biliary excretion.Following chronic oral dosing at 50, 100, and 200mg/kg/day the systemic blood levels were found to increase with dose at all time points throughout the study. There was no sex or dose dependency of the half‐life and its value on chronic dosing was very similar to that on acute dosing. The dose dependency of the area under the blood concentration time curves was reflected in the plateau blood levels and there was very good agreement between the experimental values and the theoretical relationship based on the acute pharmacokinetic data. In accordance with the half‐life there was no accumulation at any of the dose levels studied. Thus it can be concluded that atenolol obeys linear pharmacokinetics over the dose range studied.