bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivation of men and women in mathematics and language
Authors: Vrugt Anneke , Oort Frans J. , Waardenburg Lydeke
Published: October 2008

Based on the multiple goal perspective it is argued that mastery and performance goals contribute to different motivational variables—mastery goals to self‐efficacy and performance goals to social comparison—that contribute through affect to achievement. The first aim of this study was to determine whether this model is applicable irrespective of sex and subject. The expected relationships occurred for female students studying Dutch and mathematics, and for male students studying Dutch. The second aim was to test a model in which the perceived gender appropriateness of the subject affects the pursued achievement goal. We expected that subjects perceived as gender‐appropriate—Dutch for female and mathematics for male students—would result in strong relationships between mastery goals, self‐efficacy, affect, and achievement, and that less gender‐appropriate subjects—mathematics for women and Dutch for men—would result in strong relationships between performance goals, social comparison, affect, and achievement. Several of the expected relationships occurred for female and males students studying Dutch and mathematics. Furthermore, female students obtained higher course grades in Dutch than male students, while male students studying mathematics scored higher on self‐efficacy and affect than female students.
Adult hippocampal neurogenesis of mammals: evolution and life history
Authors: Amrein Irmgard , Lipp Hans-Peter
Published: October 2008

Substantial production of new neurons in the adult mammalian brain is restricted to the olfactory system and the hippocampal formation. Its physiological and behavioural role is still debated. By comparing adult hippocampal neurogenesis (AHN) across many mammalian species, one might recognize a common function. AHN is most prominent in rodents, but shows considerable variability across species, being lowest or missing in primates and bats. The latter finding argues against a critical role of AHN in spatial learning and memory. The common functional denominator across all species investigated thus far is a strong decline of AHN from infancy to midlife. As predicted by Altman and colleagues in 1973, this implies a role in transforming juvenile unpredictable to predictable behaviour, typically characterizing mammalian behaviour once reproductive competence has been attained. However, as only a fraction of mammalian species has been investigated, further comparative studies are necessary in order to recognize whether AHN has a common unique function, or whether it mediates species-specific hippocampal functions.
Parallels between playbacks and Pleistocene tar seeps suggest sociality in an extinct sabretooth cat,Smilodon
Authors: Carbone Chris , Maddox Tom , Funston Paul J , Mills Michael G.L , Grether Gregory F , Van Valkenburgh Blaire
Published: October 2008

Inferences concerning the lives of extinct animals are difficult to obtain from the fossil record. Here we present a novel approach to the study of extinct carnivores, using a comparison between fossil records (n=3324) found in Late Pleistocene tar seeps at Rancho La Brea in North America and counts (n=4491) from playback experiments used to estimate carnivore abundance in Africa. Playbacks and tar seep deposits represent competitive, potentially dangerous encounters where multiple predators are lured by dying herbivores. Consequently, in both records predatory mammals and birds far outnumber herbivores. In playbacks, two large social species, lions,Panthera leo, and spotted hyenas,Crocuta crocuta, actively moved towards the sounds of distressed prey and made up 84 per cent of individuals attending. Small social species (jackals) were next most common and solitary species of all sizes were rare. In the La Brea record, two species dominated, the presumably social dire wolfCanis dirus(51%), and the sabretooth catSmilodon fatalis(33%). As in the playbacks, a smaller social canid, the coyoteCanis latrans, was third most common (8%), and known solitary species were rare (<4%). The predominance ofSmilodonand other striking similarities between playbacks and the fossil record support the conclusion thatSmilodonwas social.
Gold bugs and beyond: a review of iridescence and structural colour mechanisms in beetles (Coleoptera)
Authors: Seago Ainsley E , Brady Parrish , Vigneron Jean-Pol , Schultz Tom D
Published: October 2008

Members of the order Coleoptera are sometimes referred to as ‘living jewels’, in allusion to the strikingly diverse array of iridescence mechanisms and optical effects that have arisen in beetles. A number of novel and sophisticated reflectance mechanisms have been discovered in recent years, including three-dimensional photonic crystals and quasi-ordered coherent scattering arrays. However, the literature on beetle structural coloration is often redundant and lacks synthesis, with little interchange between the entomological and optical research communities. Here, an overview is provided for all iridescence mechanisms observed in Coleoptera. Types of iridescence are illustrated and classified into three mechanistic groups: multilayer reflectors, three-dimensional photonic crystals and diffraction gratings. Taxonomic and phylogenetic distributions are provided, along with discussion of the putative functions and evolutionary pathways by which iridescence has repeatedly arisen in beetles.
Olfactory acuity in theropods: palaeobiological and evolutionary implications
Authors: Zelenitsky Darla K , Therrien François , Kobayashi Yoshitsugu
Published: October 2008

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds.
Interactions among co-infecting parasite species: a mechanism maintaining genetic variation in parasites?
Authors: Seppälä Otto , Karvonen Anssi , Tellervo Valtonen E , Jokela Jukka
Published: October 2008

Individuals of free-living organisms are often infected simultaneously by a community of parasites. If the co-infecting parasites interact, then this can add significantly to the diversity of host genotype×parasite genotype interactions. However, interactions between parasite species are usually not examined considering potential variation in interactions between different strain combinations of co-infecting parasites. Here, we examined the importance of interactions between strains of fish eye flukes
Diplostomum spathaceum
and
Diplostomum gasterostei
on their infectivity in naive fish hosts. We assessed the infection success of strains of both species in single-strain exposures and in co-exposures with a random strain of the other species. Parasite infection success did not consistently increase or decrease in the co-exposure treatment, but depended on the combinations of co-infecting parasite strains. This disrupted the relative infectivity of
D. spathaceum
strains observed in single-strain exposures. The infection success of
D. gasterostei
strains was independent of exposure type. These results suggest that interactions among parasite species may be strain specific and potentially promote maintenance of genetic polymorphism in parasite populations.
Spatial analysis of intracerebral electroencephalographic signals in the time and frequency domain: identification of epileptogenic networks in partial epilepsy
Authors: Wendling Fabrice , Bartolomei Fabrice , Senhadji Lotfi
Published: October 2008

Electroencephalography (EEG) occupies an important place for studying human brain activity in general, and epileptic processes in particular, with appropriate time resolution. Scalp EEG or intracerebral EEG signals recorded in patients with drug-resistant partial epilepsy convey important information about epileptogenic networks that must be localized and understood prior to subsequent therapeutic procedures. However, this information, often subtle, is ‘hidden’ in the signals. It is precisely the role of signal processing to extract this information and to put it into a ‘coherent and interpretable picture’ that can participate in the therapeutic strategy. Nowadays, the panel of available methods is very wide depending on the objectives such as, for instance, the detection of transient epileptiform events, the detection and/or prediction of seizures, the recognition and/or the classification of EEG patterns, the localization of epileptic neuronal sources, the characterization of neural synchrony, the determination of functional connectivity, among others. The intent of this paper is to focus on a specific category of methods providing relevant information about epileptogenic networks from the analysis of spatial properties of EEG signals in the time and frequency domain. These methods apply to either interictal or ictal recordings and share the common objective of localizing the subsets of brain structures involved in both types of paroxysmal activity. Most of these methods were developed by our group and are routinely used during pre-surgical evaluation. Examples are detailed. Results, as well as limitations of the methods, are also discussed.
Enhanced activity of human serotonin transporter variants associated with autism
Authors: Prasad Harish C , Steiner Jennifer A , Sutcliffe James S , Blakely Randy D
Published: October 2008

Rare, functional, non-synonymous variants in the human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT) gene (SLC6A4) have been identified in both autism and obsessive–compulsive disorder (OCD). Within autism, rare hSERT coding variants associate with rigid–compulsive traits, suggesting both phenotypic overlap with OCD and a shared relationship with disrupted 5-HT signalling. Here, we document functional perturbations of three of these variants: Ile425Leu; Phe465Leu; and Leu550Val. In transiently transfected HeLa cells, the three variants confer a gain of 5-HT transport phenotype. Specifically, enhanced SERT activity was also observed in lymphoblastoid lines derived from mutation carriers. In contrast to previously characterized Gly56Ala, where increased transport activity derives from catalytic activation, the three novel variants exhibit elevated surface density as revealed through both surface antagonist-binding and biotinylation studies. Unlike Gly56Ala, mutants Ile425Leu, Phe465Leu and Leu550Val retain a capacity for acute PKG and p38 MAPK regulation. However, both Gly56Ala and Ile425Leu demonstrate markedly reduced sensitivity to PP2A antagonists, suggesting that deficits in trafficking and catalytic modulation may derive from a common basis in perturbed phosphatase regulation. When expressed stably from the same genomic locus in CHO cells, both Gly56Ala and Ile425Leu display catalytic activation, accompanied by a striking loss of SERT protein.
Leaky Cl
−
–HCO
3
−
exchangers: cation fluxes via modified AE1
Authors: Ellory J.C , Guizouarn H , Borgese F , Bruce L.J , Wilkins R.J , Stewart G.W
Published: October 2008

The abundant membrane protein AE1 normally functions as an obligate anion exchanger, with classical carrier properties, in human red blood cells. Recently, four single point mutations of hAE1 have been identified that have lost the anion exchange function, and act as non-selective monovalent cation channels, as shown in both red cell flux and oocyte expression studies. The red cell transport function shows a paradoxical temperature dependence, and is associated with spherocytic and stomatocytic red cell defects, and haemolytic anaemias. Other forms of AE1, including the native AE1 in trout red cells, and the human mutation R760Q show both channel-like and anion exchange properties. The present results point to membrane domains 9 and 10 being important in the functional modification of AE1 activity.
The effects of repeated dermal application of capsaicin to the human skin on pain and vasodilatation induced by intradermal injection of acid and hypertonic solutions
Authors: DEL BIANCO ELENA , GEPPETTI PIERANGELO , ZIPPI PAOLA , ISOLANI DUNIA , MAGINI BEATRICE , CAPPUGI PIETRO
Published: October 2008

The effect of repeated capsaicin application on the skin of the volar surface of the forearm on the pain sensation and on the increase in blood flow induced by intradermal injection of low pH media or hypertonic solutions was investigated in 13 healthy volunteers.

Low pH media (4, and 2.5) were obtained by adding HCl to 0.9% saline. Hypertonic solutions (300 and 600 mM) were obtained by adding NaC1 to pH 7.4, 0.9% saline. Capsaicin (1% in 50% ethanol) was painted on the volar skin of one forearm, chosen at random, for 7 days. The contralateral forearm was treated with the capsaicin vehicle. Pain was assessed by a visual analogue scale and skin blood flow by a laser doppler flowmeter.

Pain sensation and increase in blood flow (both peak and area under the curve) induced by low pH media were markedly reduced in the capsaicin pretreated side. Capsaicin pretreatment also reduced the increase in blood flow, but did not affect the pain response induced by hypertonic saline solutions.

Repeated application of capsaicin to the human skin inhibits both the sensory (pain) and ‘efferent’ (vasodilatation) responses induced by low pH media, whereas it reduces the vasodilatation, but not the pain caused by hypertonic media.

Repeated application of capsaicin to the human skin, a therapy used in various diseases, discriminates between sensory, but not ‘efferent’ responses induced by different stimuli.
Triazolam pharmacokinetics and pharmacodynamics in Caucasians and Southern Asians: ethnicity and CYP3A activity
Authors: IRONS MARK T. KIN , LANG CHIM C. , HE HUAI B. , GHEBRESELASIE KEBRAB , SHAY SHEILA , ROBIN DEBORAH W. , WOOD ALASTATR J. J.
Published: October 2008

A threefold higher area under the plasma drug concentration‐time curve (AUC) of nifedipine, a substrate of cytochrome P4503A (CYP3A), has been shown in Southern Asians when compared with Caucasians. To determine if these differences are specific to nifedipine or apply to other substrates of CYP3A, we examined the pharmacokinetics and pharmacodynamics of 0.375 mg triazolam, another substrate of CYP3A, in eight healthy Caucasians and eight healthy Southern Asians in a double‐blind placebo‐controlled study. When compared with Caucasians, Southern Asians achieved higher maximum plasma concentration (Cmax) (8.0±2.6vs4.8±1.9 ng ml‐1; the 95% confidence interval (CI) of the mean difference was 0.76 to 5.7; P <0.01) and had a shorter time to reach maximal concentration (tmax) (45 min (range 30–75)vs90 min (range 60–145); the 95% CI of the mean difference was ‐69 to ‐20;P<0.002). Triazolam AUC, clearance and partial metabolic clearance did not differ significantly between Southern Asians and Caucasians. Significant differences were found in postural sway after triazolam when compared with placebo in both Caucasians (double stance:eyes open (DSEO): 172.9±82.9vs1138.9±1182.4; the 95% CI of the mean difference was ‐1897.2 to ‐ 34.4; P <0.04; and Southern Asians (DSEO: 216.2±80.9vs1086.0±827.1; the 95% CI of the mean difference was ‐1564.2 to ‐175.6;P= 0.02; double stance:eyes closed (DSEC): 207.5±89.8vs1156.9±932.1; the 95% CI of the mean difference was ‐ 1718.5 to ‐178.5;P= 0.02; with no significant difference between the two ethnic groups. These results suggest that the large inter‐ethnic difference in nifedipine clearance are not generalizable to all CYP3A4 substrates.
Effect of oxybutynin on the QTc interval in elderly patients with urinary incontinence
Authors: HUSSAIN R. M. , HARTIGAN-GO K. , THOMAS S. H. L. , FORD G. A.
Published: October 2008

Terodiline, an anticholinergic drug with calcium antagonist properties, is associated with QT prolongation and ventricular arrhythmias. It is not known if oxybutynin, a drug with a similar pharmacological profile, causes QT prolongation. ECGs were obtained before and at least 4 weeks after commencement of oxybutynin (mean daily dose 7.6, range 2.5–10 mg), in 21 elderly (mean age 75, range 58–88 years) patients treated for urinary incontinence. Heart rate, (mean±s.d.) 74±11us69±11 beats min‐1, ‒6 (‒13,2), beforeusduring oxybutynin therapy, mean difference (95% confidence intervals); PR interval, 168±27us156±27 ms, ‒11 (‒26,3); QTc 454±27us447±31 ms1 2, ‒9 (‒23,5), and QTc dispersion, QTc max‐QTc min, 68±24us63±26 ms1 2‒1 (‒15,14) were all unaltered by oxybutynin therapy. The lack of an effect on resting heart rate suggests that oxybutynin has little anticholinergic action at cardiac M2receptors at usually administered doses. Oxybutynin therapy is not associated with QTc interval prolongation and is unlikely to produce ventricular arrhythmias.
Dose dependent time course of the analgesic effect of a sustained‐release preparation of tramadol on experimental phasic and tonic pain
Authors: THÜRAUF N. , FLEISCHER W. K. , LIEFHOLD J. , SCHMID O. , KOBAL G.
Published: October 2008

The aim of this study was to investigate the analgesic effect and its duration of a new sustained‐release preparation of tramadol in an experimental pain model based on pain‐related chemosomatosensory evoked potentials (CSSEPs) and subjective intensity estimates of painful phasic and tonic stimuli.

Twenty volunteers participated in a randomised, double‐blind, three‐fold crossover study. Measurements were obtained before and 0.5, 1, 4, 6, and 12 h after administration of the drug (100 mg, 200 mg and placebo orally). CSSEPs were recorded after stimulation of one nostril with phasic, painful CO2pulses. The other nostril was stimulated with a constant stream of dry air, which produced a tonic painful sensation. Subjects rated the perceived intensity of phasic and tonic stimuli via visual analogue scales. In order to test for nonspecific effects, acoustic evoked potentials (AEPs) were recorded, the spontaneous EEG was analysed in the frequency domain, the subject's vigilance was assessed in a tracking task, and the side effects of the drug were monitored.

The sustained‐release preparation of tramadol produced a significant dose‐related decrease in CSSEP amplitudes when compared with placebo. The reduction in amplitudes outlasted the observation period of 12 h, demonstrating the prolonged duration of the analgesic effect.

A dose‐related significant decrease could be observed for the estimates of tonic pain. Similar to the decrease of amplitudes of the CSSEP, the reduction of the ratings of tonic pain outlasted the observation period of 12 h. The observed slight decrease in the estimates of phasic pain under medication did not reach a statistically significant level when compared with placebo. No significant effect could be demonstrated for the perception of the phasic and the tonic pain as determined by the McGill‐Questionnaire.

A significant dose‐related increase in the estimates of the side effects ‘drowsiness’, ‘vertigo’ and ‘sickness’ but not for ‘tiredness’ could be demonstrated.
Pharmacokinetics and tolerability of meloxicam after i.m. administration
Authors: NARJES H. , TÜRCK D. , BUSCH U. , HEINZEL G. , NEHMIZ G.
Published: October 2008

1 The pharmacokinetics and tolerability of a new nonsteroidal anti‐inflammatory drug (NSAID), meloxicam, administered i.m., were investigated in two studies conducted in healthy male volunteers. Study 1 was an open, placebo‐controlled design in which 32 volunteers were randomized to a single ascending i.m. dose of meloxicam (5, 10, 20, and 30 mg) or placebo. Study 2 had an open, randomized two way crossover design in which 12 volunteers received single i.m. and i.v. doses of meloxicam (15 mg).

2 Meloxicam showed an excellent tolerability in both studies. No effect was seen on serum creatinphosphokinase (CK, the isoenzyme of the skeletal muscle enzyme, CK‐MM, was determined).

3 Following i.m. administration meloxicam was rapidly and completely absorbed (mean absolute bioavailability 102%). Dose‐proportionality was demonstrated with respect to Cmax (maximum plasma concentration) and AUC (extrapolated area under the plasma concentration‐time curve from zero time to infinity) over a range of 5–30 mg.

4 Intravenous administration of meloxicam (15 mg) resulted in higher initial plasma concentrations (C3min, i.e. concentration in plasma 3 min after start of injection = 2.99 ± 0.75 μg·ml‐1) than after i.m. injection (Cmax: 1.62 ± 0.20 mg ml‐1). All other pharmacokinetic parameters were similar for both routes of administration (apparent elimination half‐life = 15–22 h; plasma clearance = 7–9 ml min‐1).

5 In conclusion, the excellent tolerability of i.m. meloxicam together with its rapid and complete absorption may provide an alternative to oral administration of this drug.
Venlafaxine oxidationin vitrois catalysed by CYP2D6
Authors: OTTON S. V. , BALL S. E. , CHEUNG S. W. , INABA T. , RUDOLPH R. L. , SELLERS E. M.
Published: October 2008

1 Several selective 5‐HT reuptake inhibitors (SSRIs) are inhibitors of the genetically polymorphic drug metabolizing enzyme, CYP2D6. We studied the interaction of venlafaxine, a new SSRI, with CYP2D6 in human liver microsomes.

2 Venlafaxine was a less potent inhibitor of this enzyme activityin vitrothan other SSRIs tested. The average apparentKivalues determined using CYP2D6‐dependent dextromethorphanO‐demethylation were: 33, 52 and 22 μM for rac‐venlafaxine, R(+)‐venlafaxine and S(‐)‐venlafaxine, respectively,vs0.065 to 1.8 μM for paroxetine, fluoxetine, norfluoxetine, fluvoxamine and sertraline.

3 Microsomes from human livers (n= 3) and from yeast transformed with an expression plasmid containing human CYP2D6 cDNA catalyzed theO‐demethylation of venlafaxine, which is the major metabolic pathwayin vivo.Intrinsic metabolic clearance values (Vmax/Km) indicated that S(‐)‐venlafaxine was cleared preferentiallyviathis pathway.

4 In microsomes from CYP2D6‐deficient livers (n= 2),Vmax/KmaxofO‐demethylation of venlafaxine was one to two orders of magnitude lower and was similar to the rate ofN‐demethylation.

5 Studies with chemical probes which preferentially inhibit P450 isoforms suggested that CYP3A3/4 is involved in venlafaxineN‐demethylation.

6 Thesein vitrofindings predict phenotypic differences in the kinetics of venlafaxinein vivo, although the clinical importance of this is unclear asO‐demethylvenlafaxine is pharmacologically similar to the parent drug. The findings also predict relatively limited pharmacokinetic interaction between venlafaxine and other CYP2D6 substrates.
low molecular weight heparin, nadroparin (Fraxiparine), inhibits thrombin‐induced platelet shape change and does not enhance spontaneous platelet aggregation
Authors: JAGKOOP I. A. , BARRADAS M. A. , MIKHAILIDIS D. P.
Published: October 2008

Therapeutic concentrations, added in vitro, of a low molecular weight heparin (LMWH), nadroparin (Fraxiparine), inhibit thrombin‐induced platelet shape change (PSC), an early stage of human platelet activation. PSC was monitored by measuring the median platelet volume (MPV) using a high resolution channelyzer. The inhibitory action of nadroparin was specific to thrombin since this LMWH did not influence PSC induced by other agonists. In whole blood, unfractionated heparin (UH) but not nadroparin, significantly enhanced spontaneous olatelet aggregation and increased MPV when compared with LMWH or saline controls. In conclusion, the LMWH, nadroparin, exerts less platelet activation than UH.
Pharmacokinetic evaluation of proguanil: a probe phenotyping drug for the mephenytoin hydroxylase polymorphism
Authors: SOMOGYI ANDREW A. , REINHARD HELEN A. , BOCHNER FELIX
Published: October 2008

1 Proguanil (PG) oxidative metabolism to cycloguanil (CG) has been linked to the CYP2C19–mediated genetic polymorphism in S‐mephenytoin oxidative metabolism. In many countries, rac‐mephenytoin can no longer be administered to humans and hence proguanil may be a more suitable probe for phenotyping purposes.

2 There are limited data on the pharmacokinetics of PG and CG and in particular, whether there is a relationship between the urinary metabolic ratio of PG and its partial intrinsic clearance to CG.

3 The disposition of a 100 mg oral dose of PG was investigated in 10 subjects with widely varying metabolic ratios (pre‐study urinary metabolic ratio CG to PG = 0.068 to 1.11). Blood samples and all urine were collected for 96 h and assayed for PG and CG by h.p.l.c.

4 The urinary recovery of PG ranged from 30 to 69% of the dose and for CG from 2.8 to 32% of the dose. The overall urinary recovery of PG plus CG ranged from 54 to 77% of the dose. The AUC for PG ranged from 3.2 to 9.5 mg 1‐1 h whereas for CG it was from 0.02 to 0.71 mg 1‐1 h. The partial intrinsic clearance to CG ranged 25–fold from 0.41 to 10.11 h‐1

5 There was a highly significant (r2= 0.96, P < 0.001) relationship between the urinary metabolic ratio for PG (as CG/PG) and its partial intrinsic clearance to CG.

6 These data have provided evidence for the justification of the use of the urinary metabolic ratio of proguanil for population phenotyping purposes, provided systematic variation in renal drug clearance between populations is considered.
In vitrointeraction of the antipsychotic agent olanzapine with human cytochromes P450 CYP2C9, CYP2C19, CYP2D6 and CYP3A
Authors: RING BARBARA J. , BINKLEY SHELLY N. , VANDENBRANDEN MARK , WRIGHTON STEVEN A.
Published: October 2008

1 The ability of olanzapine to inhibit the metabolism of marker catalytic activities for the cytochromes P450 CYP3A, CYP2D6, CYP2C9, and CYP2C19 was examined. This inhibitory capability was compared with that obtained with clozapine and known inhibitory compounds for the same cytochromes P450.

2 Olanzapine, clozapine, and ketoconazole were all found to non‐competitively inhibit 1′‐hydroxy midazolam formation, form selective for CYP3A, yieldingKi, values of 491, 99 and 0.11 μM, respectively. The 1′‐hydroxylation of bufuralol, form selective for CYP2D6, was competitively inhibited by olanzapine (Ki= 89μM), clozapine (Ki= 19 μM), and quinidine (Ki= 0.03 μM). Tolbutamide metabolism to 4–hydroxy tolbutamide, form selective for CYP2C9, was competitively inhibited by clozapine and phenytoin (Kiof 31 μM and 17 μM, respectively). Olanzapine non‐competitively inhibited tolbutamide metabolism with aKiof 715 μM. The marker catalytic activity for CYP2C19 mediated metabolism, 4′‐hydroxy S‐mephenytoin formation, was competitively inhibited by clozapine (Ki= 69 μM) and omeprazole (Ki= 4.1 μM). Non‐competitive inhibition of CYP2C19 mediated metabolism was seen with olanzapine with aKiof 920 μM.

3 The calculated percent inhibition by olanzapine of substrates metabolized by CYP3A, CYP2D6, CYP2C9, and CYP2C19 was modeled assuming a total plasma concentration in the therapeutic range (0.2 μM). Total olanzapinevsunbound olanzapine was used to model the worst case (most conservative) situation. In all cases, the calculated percent inhibition of these cytochromes P450 by olanzapine was <0.3%, suggesting that there would be littlein vivoinhibition of the metabolism of substrates of these enzymes when co‐administered with olanzapine.
Identification of drugs inhibiting thein vitrometabolism of tacrolimus by human liver microsomes
Authors: CHRISTIANS UWE , SCHMIDT GUDRUN , BADER AUGUSTINUS , LAMPEN ALFONS , SCHOTTMANN RENATE , LINCK ANNETTE , SEWING KARL‐FRIEDRICH
Published: October 2008

1 Tacrolimus, an immunosuppressive macrolide, is metabolized by enzymes of the cytochrome P450 3A subfamily. In this study, 34 drugs were tested for their interactions with tacrolimus metabolism by human liver microsomes.

2 Fifteen drugs which inhibit thein vitrometabolism of tacrolimus were identified: bromocriptine, corticosterone, dexamethasone, ergotamine, erythromycin, ethinyloestradiol, josamycin, ketoconazole, miconazole, midazolam, nifedipine, omeprazole, tamoxifen, troleandomycin and verapamil.
A pharmacokinetic interaction study of didanosine coadministered with trimethoprim and/or sulphamethoxazole in HIV seropositive asymptomatic male patients
Authors: SRINIVAS N. R. , KNUPP C. A. , BATTEIGER B. , SMITH R. A. , BARBHAIYA R. H.
Published: October 2008

R. A. SMITH3

1 The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses.

2 Using a randomized, balanced incomplete block crossover study with at least a 1–week washout period between successive treatments, each patient under fasting conditions received four of the following five treatments: 200 mg didanosine as a single agent; 200 mg trimethoprim +1000 mg sulphamethoxazole; 200 mg trimethoprim + 200 mg didanosine; 1000 mg sulphamethoxazole + 200 mg of didanosine and; 200 mg trimethoprim +1000 mg sulphamethoxazole + 200 mg didanosine.

3 Serial blood and urine samples were collected following the administration of each treatment. Plasma and urine samples were analyzed using high‐pressure liquid chromatography (h.p.l.c.)/ultraviolet assays specific for unchanged didanosine, trimethoprim and/or sulphamethoxazole.

4 Percent urinary recovery (%UR) and renal clearance (CLR) emerged as consistently affected parameters, being decreased in the case of didanosine (35%,P= 0.016) and trimethoprim (32%,P= 0.019) and increased in the case of sulphamethoxazole (39%,P= 0.079), when all three agents were coadministered. The magnitude of the changes in didanosine CLRand %UR values was no greater when both trimethoprim and sulphamethoxazole were coadministeredvswhen each single agent was given with didanosine, suggesting that any effect was not additive.

5 Other key parameters such as CmaxAUC, andt1/2for didanosine (1309.9 ng ml‐1, 1796.9 ng ml‐1h, and 1.61 h, respectively), trimethoprim (1.96 pg ml‐1, 22.86 μg ml‐1h, and 9.03 h, respectively) or sulphamethoxazole (58.62 μg ml‐1, 799.7 μg ml‐1h and 9.84 h, respectively) were not affected when didanosine was coadministered with either trimethoprim (didanosine: 1751.9 ng ml‐1, 2158.0 ng ml‐1h, and 1.28 h; trimethoprim: 1.81 μg ml‐1, 28.89 μg ml‐1h, and 11.4 h), sulphamethoxazole (didanosine: 1279.3 ng ml‐1, 1793.2 ng ml‐1h, and 1.61 h; sulphamethoxazole: 53.57 μg ml‐1, 732.1 μg ml‐1h, and 8.95 h), or the combination of trimethoprim and sulphamethoxazole (didanosine: 1283.7 μg ml‐1, 1941.8 ng ml‐1h, and 1.38 h; trimethoprim: 1.59 μg ml‐1, 26.68 μg ml‐1h, and 11.3 h; sulphamethoxazole: 59.48 μg ml‐1, 760.9 μg ml‐1h, and 9.47 h).

6 Because the observed differences in CLRand %UR are small and not considered to be clinically relevant, it is not necessary to alter the dosing regimens of didanosine, trimethoprim or sulphamethoxazole when administered in combination to HIV seropositive patients.
Lack of interaction between flucloxacillin and methotrexate in pa tien t s with rheumatoid arthritis
Authors: HERRICK ARIANE L. , GRENNAN DAVID M. , GRIFFEN KERRY , AARONS LEON , GIFFORD LARRY A.
Published: October 2008

1 The aim of the study was to examine the potential pharmacokinetic interaction between methotrexate and flucloxacillin.

2 Ten rheumatoid arthritis patients participated in the interaction study. Subjects were allocated to either methotrexate alone (5–15 mg per week) or methotrexate plus flucloxacillin (500 mg four times a day 48 h prior to sampling) in a random order.

3 There was a statistically, but not clinically, significant decrease in methotrexate AUC (1307 ± 389vs1212 ± 394 μg 1‐‐1h) in the presence of flucloxacillin. Cmaxand tmaxparameters for methotrexate were not significantly altered in the presence of flucloxacillin.

4 Data from an additional 10 rheumatoid arthritis patients, starting on methotrexate, were added to the data from the placebo arm of the interaction study and a model dependent pharmacokinetic analysis was performed. The plasma concentration profiles were best described by a two‐compartment model with a mean clearance of 11.9 (± 1.7) 1 h‐1and an initial volume of distribution of 31.2 (± 2.6) 1. The pronounced intersubject variability in the pharmacokinetic parameters was not related to any of the available covariate information.

5 Our findings suggest that no important clinical interaction occurs between flucloxacillin and methotrexate in patients with rheumatoid arthritis.
Lung bioavailability of chlorofluorocarbon free, dry powder and chlorofluorocarbon containing formulations of salbutamol
Authors: CLARK D. J. , LIPWORTH B. J.
Published: October 2008

With the future advent of a world wide ban on chlorofluorocarbon containing aerosols, a study was designed to compare the in vivo lung bioavailability of salbutamol via chlorofluorocarbon‐containing metered‐dose inhaler (CFC), chlorofluorocarbon‐free metered‐dose inhaler (CFC‐free), and dry powder inhaler (DPI). Twelve healthy male subjects were given 1200 μg salbutamol and measurements made of plasma and urinary salbutamol. CFC‐free produced significantly higher plasma salbutamol levels (ng ml‐1; mean and 95% CI for difference) than either CFC or DPI: Cmax, CFC‐free 4.18 vs CFC 3.29 (95% CI 0.10–1.68), vs DPI 3.42 (95% CI ‐0.03–1.56). The ratio for the difference in Cmax between CFC and CFC‐free formulations was 1.32 (95% CI 1.02–1.61). There were no significant differences between CFC and DPI formulations. Urinary salbutamol results did not reveal any significant differences between the three inhalers (μg 30 min‐1): CFC‐free 42.4, CFC 43.8, DPI 45.3. Thus, the lung bioavailibility of CFC‐free was greater than that of CFC or DPI formulations of salbutamol.
THE USE OF ULTRASONICS IN STRESS ANALYSIS
Authors: CRECRAFT D. I.
Published: October 2008

Abstract:Some methods that have been proposed for ultrasonic stress analysis are described. These depend on the measurement of stress‐induced velocity changes, analogous to the light‐wave velocity changes in photoelasticity. The theory of the nonlinear stress‐strain relationships giving rise to the velocity changes is introduced, and the practical and fundamental difficulties yet to be resolved are pointed out. The results of some measurements of stress‐induced changes are quoted.
STRESSES DUE TO CONCENTRATED LOADS IN RESTRAINED BENDING TESTS
Authors: CHEUNG Y. K. , DAVIES J. D. , NATH P.
Published: October 2008

The paper describes an analytical method using finite element techniques for evaluating the “pinching” stresses in a beam subjected to opposing concentrated forces acting on upper and lower faces. These conditions arise in restrained modulus of rupture tests on concrete beams when it is required to know the magnitude of these local stress concentrations in relation to the normal “straight line” flexural stress field.

The analytical values are compared with results taken from a photo‐elastic model with suitably simulated loading conditions. There is excellent correlation between the patterns of principal shear contours as plotted from the finite element solution and the isochromatic lines observed in the loaded model.
AN INEXPENSIVE ULTRA‐HIGH‐SPEED PHOTOGRAPHIC TECHNIQUE
Authors: TSCHINKE M.
Published: October 2008

Commercial Ultra‐High‐Speed Cameras for framing rates over 50,000 f.p.s. are very expensive and yield a small number of frames (8 to 24) per run. The single‐flash technique with increasing delays gives photographs at a high framing rate over a comparatively long time and, as described here, requires no special electronic equipment except a good flash unit and a general‐purpose oscilloscope.
BRITTLE COATINGS SUITABLE FOR USE ON LARGE OBJECTS
Authors: FLEAR B. S.
Published: October 2008

In order to determine the positions of high stress on large turbine components like ducting, casings, etc., tests were made with various brittle coatings. The coating must cure at room temperature, be insensitive to change in temperature and humidity, be unaffected by immersion in water, have no toxic effects and be sensitive to strains less than the yield strain of mild steel. Robert Ingham Clark's Stress Lacquer R.V. 519 was found to satisfy these requirements.
SEPARATION OF PRINCIPAL STRESSES ALONG SECTIONS OF SYMMETRY BY MEANS OF ISOPACHIC PATTERNS
Authors: AJOVALASIT A.
Published: October 2008

An approximate rapid method for the separation of principal stresses along sections of symmetry free from external loads is described. The method is based on the sum of principal stresses and checked by applying it to a circular ring under diametral compression and to a grooved bar in tension.
A LONG NARROW FOIL STRAIN GAUGE FOR SPECIAL PURPOSES
Authors: HAYHURST D. R. , PENNY R. K.
Published: October 2008

The development of a narrow (0.015 in), long (1.48 in) foil strain gauge is described for sensitive measurement of average localised strains, for instance the average tangential strain along the circumference of a hole in a plate under uniaxial or equi‐biaxial tension. Good agreement between measured and analytical values has been obtained.
TECHNIQUES FOR THE RECORDING AND MEASUREMENT OF CRACK GROWTH DURING FATIGUE AND FRACTURE TOUGHNESS TESTING
Authors: ADAMS N. J. I. , MUNRO H. G.
Published: October 2008

This note presents details of three techniques of monitoring and recording crack growth during fracture testing. The first technique uses special foil gauges, the second extends potential‐flow measurements to asymmetric crack growth; the third uses an acoustic pick‐up to detect intermittent crack growth in plane‐strain fracture toughness testing.
THE MECHANICAL PROPERTIES OF SOME POLYURETHANE RUBBERS AT ROOM TEMPERATURE
Authors: McNICHOLAS J. B. , RANKILOR P. R.
Published: October 2008

Article describes the casting of polyurethane rubbers and difficulties in determining Young's Modulus of such a soft rubbery material. Suitable testing procedures are recommended for the wide range of moduli from 16 to 700 lbf/in2 obtainable with different mixes of this material, their fringe‐stress sensitivities are measured and favourable technical applications are pointed out.
A NEW STRESS GAUGE OF VARIABLE MODULUS
Authors: GIBBS J. R.
Published: October 2008

An embedded stress sensing head is connected hydraulically to a control cell on a slug which possesses the properties of the host material removed to make place for the sensing head. The hydraulic pressure is regulated by a compensator so that the deformation of the slug is always the same as that of the cavity made for the sensing head.
LASER PRODUCED MOIRÉ GRATINGS
Authors: BOONE P.
Published: October 2008

A new method for producing high frequency moire gratings is based on the interference between two monochromatic waves in a photographic medium. A short theory and some experimental results are given.
A SIMPLE TELEMETERING SYSTEM FOR STRAIN MEASUREMENT
Authors: IVISON J. M. , BLANCHARD J.
Published: October 2008

A simple short‐range telemetering system has been adapted for use with strain gauges and two applications are described, a transducer measuring displacements and a circuit with two semi‐conductor gauges measuring torque on a shaft.
THE SANDWICH TECHNIQUE IN PHOTOELASTICITY
Authors: LAMBLE J. H.
Published: October 2008

A methyl methacrylate composition of exactly zero birefringence has been developed and the technique of its application to the sandwich method with a birefringent layer of Araldite is described in detail with special consideration of the problems of cementing the two different materials. Tensile and bending tests on bars with stress concentrations demonstrate the validity of the method.
DISTRIBUTION IN AN EXTRUSION CONTAINER, FOUND BY THE SANDWICH TECHNIQUE
Authors: EL‐BEHERY A. M. , LAMBLE J. H.
Published: October 2008

Commercial Perspex and “Perspex” of zero birefringence are applied in an investigation by the sandwich technique of the stress in a transverse section of a container from which lead is extruded through a die. The use of commercial Perspex in this application is shown to give rise to errors which are avoided by the new material of zero birefringence. The principal stresses in the birefringent layer of the sandwich are evaluated.
ROOM TEMPERATURE THREE‐DIMENSIONAL PHOTOELASTIC MODEL STUDY OF A COMPLEX AIRFRAME COMPONENT
Authors: Sweet H. J. , Cano N. O.
Published: October 2008

The use of optically isolated layers within a complex three‐dimensional model permits a photoelastic analysis in their planes at room temperatures. A programme was undertaken to determine experimentally the state of stress in, and the structural behaviour of a portion of the aft bulkhead of an Fill aircraft in order to improve the fatigue life of the component. Information obtained about its behaviour under load clearly indicates the usefulness of this technique as a design tool; its general advantages and disadvantages are discussed by comparison with the stress freezing and slicing technique.
A MEGOHMMETER FOR THE MEASUREMENT OF THE INSULATION RESISTANCE OF CERAMIC INSTALLATIONS FOR STRAIN GAUGES
Authors: MATHERS J.
Published: October 2008

A megohmmeter capable of measuring insulation resistances between 0:1 and 100 megohm at temperatures up to 900°C is described and its main electric circuits are indicated.
MOIRÉ FRINGE MULTIPLICATION WITH A SPATIALLY FILTERING PROJECTION SYSTEM
Authors: BOONE P. , van BEECK W.
Published: October 2008

The paper describes a method of multiplying the basic frequency of a deformed grating by filtering in the Fourier plane of a lens. The moiré pattern is formed in the image plane of this lens by mechanical interference of a frequency‐multiplied enlarged image of the specimen grating with a reference grating. A theoretical description of the system is given and some experimental results are presented.
STENCIL METHODS FOR PREPARING MOIRE GRIDS
Authors: LUXMOORE A. , HERMANN R.
Published: October 2008

Three methods are described for depositing moiré grids on specimens by means of thin metal meshes produced by electroforming. The methods involve printing, electro‐etching, vacuum deposition, with the mesh used as a stencil, and they are capable of accurately reproducing grids with line densities of 2000 lines/in (80 lines/mm) and of giving good contrast.
PREDICTION OF ZERO STRAIN VECTORS IN DYNAMOMETER RINGS
Authors: SCOTT C. K. W. , DROUBI G.
Published: October 2008

A simplified theory for the prediction of points of zero strain in dynamometer rings under diametral loads has been verified by experiment and found to give very good results. These points can be used for the separation by strain gauge indications of the effects of two mutually perpendicular forces.
A RAPID METHOD FOR CALCULATING THE TRANSVERSAL STRAIN IN THE MOIRE TECHNIQUE ALONG SECTIONS OF SYMMETRY
Authors: de GREGORIO G.
Published: October 2008

An approximate rapid method is described for calculating in the moiré technique the transversal strain directly from the longitudinal strain distribution across sections of symmetry. The method is based on evaluation of the load transmitted through the section and is corroborated by two examples.
Lensless photography of gratings
Authors: de CALUWE M. , BOONE P. , van BEECK W.
Published: October 2008

A technique is described for the preparation of contact‐copy prints of gratings by means of reflex photography. The authors suggest that the method gives increased contrast and definition compared with classical methods of preparing prints.
Measurement of stress waves in impacted frames
Authors: ATKINS K. J.
Published: October 2008

Bars of 1 in (25 mm) square section and frames made up of such bars are impacted at various points and the development of ensuing vibrations is studied by means of strain gauges. Experimental methods and recording equipment normally used for relatively slow impact tests are described.
Measurements of static strains on titanium under rapid heating
Authors: LEMON T. E. H.
Published: October 2008

The behaviour of various strain gauges on unstressed titanium IMI 317 under various heating rates is investigated systematically. Testing methods, gauge preparation, evaluation of tests and results are presented.
Elastic stresses between curved bodies in rolling contact
Authors: OLLERTON E.
Published: October 2008

An outline of the development of the elastic theory of contact stresses is presented. The literature is discussed in some detail, and equations for the sub‐surface stresses are given for several important cases. The effects of surface shear stresses associated with tangential forces and rolling with spin are also considered.
Two FORTRAN programs for rosette calculations
Authors: COCKRILL M.
Published: October 2008

These programs calculate principal stresses, strains and directions from any rosette readings. The appropriate values are read in, the angles placed in the range 0 to 180° and the strains arranged in descending order. Next the necessary quantities are calculated and checked; a choice of output formats is provided together with an error message and diagnostic information if the check fails. One of the programs is written to accept strain readings on punched cards, the other accepts voltage readings on paper tape from a data logger. The programming language is FORTRAN IV. The programs have been used on an ICL 1903A computer.
Measurement of elastic constants using vibrating wire strain gauges on disc and ring specimens
Authors: MACDUFF I. B.
Published: October 2008

Useful methods of determining elastic constants employing diametrically–loaded disc and ring specimens have been proposed and applied by Durelli and Ferrer. Young's modulus may be measured from tests on a suitably dimensioned ring specimen. Subsequently Poisson's ratio may be found using a disc. The application of the methods described by the authors does not suit the case where the specimens are small and of stiff materials such as metals. In such a case sensitive means are required for measuring change in diameter with light loading. The paper indicates how this can be carried out for an aluminium alloy. The theory relating to the use of the disc for determining Poisson's ratio has been generalised to allow for measurement of change in length over part or all of a diameter. Poisson's ratio of the aluminium alloy was determined with a disc specimen 0.874 in (22.2 mm) diameter, vibrating wire strain gauges on either side of the specimen indicating change in diameter with loading. A ring was subsequently machined from the disc and similarly tested to confirm Young's modulus.
The manufacture of highly accurate model structural members by nickel electrode position
Authors: TILLMAN S. C.
Published: October 2008

Practical details are presented for making thin–walled model structural members by the method of nickel electrode position. The elastic members so produced are highly accurate in profile, possess small thickness variations and are also stress free, thus making them very suitable for stress analysis or stability studies.