bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of the effects of potassium channel modulating agents on mouse intestinal smooth muscle
Authors: Yeung Chi-Kong , McCurrie Janice R , Wood Diana
Published: October 2002

The actions of agents which modulate ATP-sensitive potassium (KATP) channels in excitable cells were investigated in an in-vitro preparation of mouse ileum from which the mucosa was removed. A range of potassium channel openers of diverse structure, cromakalim (0.1–100 μM), pinacidil (0.1–200 μM) and its analogue P1060 (0.1–200 μM), SDZ PCO400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile) (0.3–60 μM), caused concentration-related reduction in twitch height of electrical field stimulated ileum. P1060 and SDZ PCO400 were the most potent agents; diazoxide (0.1–100 μM) was without effect. The order of inhibitory potency, based on EC50 values (concentration of a relaxant producing 50% of the maximum inhibition of twitch) was: P1060 = SDZ PCO400 > cromakalim > pinacidil. The relaxant effect of the potassium channel openers was antagonised by the sulfonylureas glibenclamide (0.1-1.0 μM) and glipizide (3–30 μM) but the nature of the antagonism differed. Antagonism of P1060 and SDZ PCO400 by glibenclamide appeared to be competitive whereas the antagonism of relaxation induced by cromakalim and pinacidil was apparently not competitive. Both phentolamine (1–10 μM) and tolbutamide (100–300 μM) showed competitive antagonism of the actions of pinacidil while yohimbine (1–20 μM) did not antagonise relaxation and appeared to have actions at sites other than the KATP channel in this preparation. The relative effectiveness of the antagonists on pinacidil-induced relaxation was found to be: glibenclamide >phentolamine >tolbutamide >yohimbine, which is in agreement with studies in other tissues. The results show that many structurally diverse potassium channel openers are potent relaxants of mouse ileum. These observations are consistent with the existence of ATP-dependent K+ channels in murine intestinal muscle which, however, differ somewhat in properties from those reported for vascular muscle and pancreatic β-cells.
Sensitivity of dissolution rate to location in the paddle dissolution apparatus
Authors: Healy A M , McCarthy L G , Gallagher K M , Corrigan O I
Published: October 2002

The aim of the present study was to determine the apparent diffusion boundary layer and dissolution rate constant for various surfaces of compacts and at various locations in the USP paddle dissolution apparatus. Benzoic acid compacts were coated with paraffin wax leaving only the surface under investigation free for dissolution. The dissolution rates for various surfaces at varying locations in the paddle dissolution vessel were determined from the slope of the dissolution profile (amount dissolved (mg) versus time (min)). The apparent diffusion boundary layer and dissolution rate constant were calculated and were found to vary depending on the surface of the compact from which dissolution took place and also on the location and size of the compact. It may be concluded that, in developing models to describe the dissolution from solid dosage forms, it is not accurate to assume constant hydrodynamics and mass transfer rates at all surfaces of the system, or in different locations within the test device. A more exact description of the hydrodyn amics would be necessary in order to precisely model drug dissolution in the paddle dissolution apparatus.
The study on organic nitrates, part V. New derivatives of piperazine potential NO donors
Authors: Korzycka Lucyna
Published: October 2002

We have obtained a series of non-symmetrical 1,4-disubstituted derivatives of piperazine, with the structure of organic nitrates, as potential NO donors. These compounds were obtained from respective hydroxyl derivatives of piperazine in an esterification reaction by fuming nitric acid. The obtained nitrates were tested in-vitro by reaction with a sulfhydryl compound. The structure of the most active nitrate and its hydroxyl analogue was used for the calculation of geometrical optimization with the determination of 3D-QSAR by a semi-empirical method PM3 using HyperChem 4.5.
Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue
Authors: Hopkins Ann M , McDonnell Ciara , Breslin Niall P , O'Morain Colm A , Baird Alan W
Published: October 2002

Triple therapy using proton-pump inhibitors (PPIs) in combination with oral antibiotics for the treatment of Helicobacter pylori-associated gastritis has shown increased efficacy for reasons that are still poorly understood. Possible explanations include a direct antibacterial effect of the PPIs or a PPI-mediated increase in bacterial susceptibility to antibiotics. Using an in-vitro model of rat gastric mucosa, we examined fluxes of a radiolabelled marker molecule through the interepithelial tight junctions under normal conditions and under the influence of an acid secretagogue (50 μM histamine) and a PPI (100 μM omeprazole). Paracellular fluxes of the radiolabel (represented by calculation of apparent permeability coefficients) were linear over 2 h. Fluxes of the marker increased significantly after treatment with histamine followed by omeprazole, but were unaltered in paired preparations exposed to the same drugs given in reverse order. Enhancements in paracellular permeability were mirrored in separate experiments using a detergent (Triton X-100), a bile salt (deoxycholate) and an agent that disrupts the cytoskeleton (cytochalasin D) to interfere with tight junctional integrity. The results suggest that exposure of acid-secreting gastric mucosa to omeprazole widens the interepithelial spacing in a manner that may facilitate enhanced macromolecular transport. Increases in antibiotic delivery from the blood to the gastric lumen via such a mechanism may account for the greater eradication rates observed with PPI-based triple therapy in H. pylori-associated gastritis.
Anti-inflammatory and antioxidant properties of Helichrysum italicum
Authors: Sala Araceli , Recio María del Carmen , Giner Rosa María , Máñez Salvador , Tournier Horacio , Schinella Guillermo , Ríos José-Luis
Published: October 2002

The anti-inflammatory and antioxidant activities of the aerial part of Helichrysum italicum extracts have been established in various in-vivo and in-vitro experimental models. The results obtained on the acute oedemas induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) and ethyl phenylpropiolate in the mouse ear, by serotonin and phospholipase A2 (PLA2) in the mouse paw, on chronic inflammation induced by repeated application of TPA in the mouse ear and on the delayed-type hypersensitivity induced by sheep red blood cells suggest that said anti-inflammatory activity is due to the effects of compounds expressed via a corticoid-like mechanism. In addition, the antioxidant activity of the extracts seems to be implicated in this anti-inflammatory activity, as the former inhibits enzymatic and non-enzymatic lipid peroxidation and has free-radical scavenger properties. We conclude that the anti-inflammatory activity of Helichrysum italicum can be explained by multiple effects, including inflammatory enzyme inhibition, free-radical scavenging activity and corticoid-like effects.
1-0-Hexyl-2,3,5-trimethylhydroquinone inhibits IκB phosphorylation and degradation-linked inducible nitric oxide synthase expression: beyond antioxidant function
Authors: Liu Wei , Itoigawa Masataka , Miki Tokutaro , Nishikawa Hiroshi , Sugiyama Satoru , Ishikawa Naohisa
Published: October 2002

Inducible nitric oxide (NO) production in macrophages plays an important role in atherosclerosis, the protective effects of vitamin E and its derivatives perhaps being partly mediated by alteration in this parameter. We have investigated the influence of a novel synthesized vitamin E derivative, 1-0-hexyl-2,3,5-trimethylhydroquinone (HTHQ), on NO production in the RAW 264.7 mouse macrophage cell line. HTHQ dose-dependently inhibited lipopolysaccharide (LPS)-induced NO production through reducing LPS-triggered inducible nitric oxide synthase (iNOS) expression. The phosphorylation and subsequent degradation of IKB caused by LPS in RAW 264.7 cells was markedly blocked. The free radical scavenging activity of HTHQ was only 2-fold that of vitamin E, whereas its inhibition of NO production was found to be nearly 500-fold stronger. Our results indicated that HTHQ suppressed NO production in macrophages by blocking IKB degradation and thus inhibiting iNOS expression. The inhibitory activity of HTHQ on NO production did not parallel its free radical scavenging activity, implying a possible involvement of additional functions.
Synthesis and spasmolytic action of 2-substituted thienopyrimidin-4-one derivatives
Authors: Santagati Natale Alfredo , Prezzavento Orazio , Bousquet Ennio , Ronsisvalle Giuseppe , Spampinato Santi
Published: October 2002

In the search for novel compounds to treat disorders of smooth muscle function, efforts have focused on some 2-substituted thieno[2,3-d]pyrimidin-4-onederivatives that show interesting spasmolytic action. Our laboratories have developed a new series of quaternary salts of 2-substituted thieno[2,3-d]pyrimidin-4-one and thieno[3,2-d]pyrimidin-4-oneisomers with therapeutic potential. These substances were prepared starting from simple derivatives of thiophene. Their spasmolytic activity was evaluated on transmurally stimulated guinea-pig ileum. The most active compounds (IC50 1.12-2.71 μM) 7f-7h, 12d and 12f had the terminal piperidino nucleus in the thioalkyl chain and lacked two methyl groups in the thiophene ring. Their relaxant activity on the isolated ileum was potentiated (approx. 20–25%) by phosphodiesterase inhibitors. Compounds 7f-h, 12d and 12f were less effective in inhibiting contractions of the guinea-pig ileum induced by acetylcholine (IC50 26.7–41.4 μM) or histamine (IC5041.5–63.4 μM) and had a moderate binding activity to muscarinic receptors in membrane homogenates from the rat heart (M2 sites; pKi values between 5.55 ± 0.08 and 5.14 ± 0.12; n = 3) and submaxillary gland (M3 sites; pKi values between 6.15 ± 0.07 and 5.76 ± 0.08; n = 3). Action involving soluble guanylyl cyclase or any potential binding to guinea-pig ventricular L-type calcium channels was not considered likely. It is concluded that at least two different mechanisms of action contribute to their spasmolytic activity.
Concentration-dependent disposition of glucuronide metabolite of valproate
Authors: Yu Hsiu-Ying , Shen Yu-Zen
Published: October 2002

The glucuronide conjugation metabolism of valproate (VPA) has been assessed to be non-linear within the therapeutic concentration range. However, disposition of its metabolite, valproic acid glucuronide (VPAG), in relation to VPA doses is unclear. The purpose of this study was to elucidate the characteristics of dose-related disposition of VPAG. Guinea-pigs were treated with an intravenous bolus dose of sodium valproate at 20, 100, 500 or 600 mg kg−1. Plasma was sampled on a pre-selected time schedule, and bile and urine were collected. Concentrations of VPA and VPAG in plasma, bile and urine were determined by gas chromatography. The pharmacokinetics of VPA and VPAG both were dose-dependent. However, the plasma concentration-time profiles of VPAG and VPA were not parallel. At a usual dose of VPA (20 mg kg−1) plasma VPAG declined with plasma VPA, whereas at a high dose of VPA (> 500 mg kg−1) plasma VPAG was elevated against the decline of plasma VPA, which suggested accumulation of plasma VPAG possibly owing to saturated elimination. The biliary and urinary clearances of VPA (vCLb and vCLu) were independent of dose. However, the clearances of plasma VPA (vCLp), plasma VPAG (gCLp), biliary and urinary VPAG (gCLb and gCLu) all were decreased against the increase in VPA doses. The dose-dependent decrease of gCLu (from 3.19 to 1.12 mL min−1) was less pronounced than that of gCLp (from 6.72 to 0.86 mL min−1) and the gCLu turned to exceed the gCLp at high doses of VPA (> 500 mg kg−1). These results suggest that the excess urinary VPAG might be produced in kidney. In conclusion, at a high dose of VPA, plasma VPAG is accumulated. The concentration-dependent biliary and urinary recovery of VPAG might be governed by a saturable elimination process rather than by saturable hepatic biotransformation rate. Glucuronide conjugation metabolism of VPA in kidney is speculated, which might be minor at low levels of plasma VPA, but more obvious after saturation of hepatic glucuronidation.
Multiple dose pharmacokinetics of fiduxosin under fasting conditions in healthy elderly male subjects
Authors: Dutta Sandeep , Zhang Yiming , Daszkowski Daniel J , Granneman G Richard , Verlinden Marleen
Published: October 2002

Selective α1a-adrenoceptor antagonists are effective agents for treatment of benign prostatic hyperplasia, a disorder occurring in middle-aged and elderly males. The objective of this study was to determine the pharmacokinetics of fiduxosin, a novel α1a-adrenoceptor antagonist, following multiple dose administration. This was carried out in a Phase I, randomized, double-blind, placebo-controlled, parallel group, multiple oral dose study of fiduxosin. Single once-daily oral doses of 30, 60, 90 or 120 mg of fiduxosin or placebo were administered to healthy elderly male subjects (n = 48; 8 active and 4 placebo per dosing group) for 14 consecutive days. Fiduxosin plasma concentration-versus-time prof les for days 1, 7 and 14 were used to assess fiduxosin pharmacokinetics. Steady state was achieved by day 7. At steady-state mean Tmax (time to maximum plasma concentration), CL/F (apparent oral clearance) and Vβ/F (apparent volume of distribution) ranges were 1.8-7.8h, 27.3–47.2 L h−1 and 846-1399L, respectively. Tmax and Vβ/F were independent of dose. Cmax (maximum plasma concentration), Cmin (minimum plasma concentration) and AUC24 (area under plasma concentration vs time curve from 0 to 24 h) for days 7 and 14 were linearly proportional with dose over the 30–120 mg/day dose range and were unchanged from day 7 to day 14. It was concluded that fiduxosin multiple-dose pharmacokinetics were dose-independent and time-invariant over the 30–120 mg/day dose range under fasting conditions.
Pharmaceutical quality of different Ginkgo biloba brands
Authors: Kressmann S , Müller W E , Blume H H
Published: October 2002

Ginkgo biloba-containing brands are one of the top sellers within the growing market for herbal remedies in many European countries as well as in the USA. In the consumers' interest, these brands should feature a certain quality and should be transparent in quality claims. In this investigation, a variety of products on the USA market was studied with respect to pharmaceutical quality, such as quantity of constituents and in-vitro dissolution. In terms of the content of active substances, flavone glycosides ranged from 24% to 36% and terpene lactones from 4% to 11%. With ginkgolic acids, there was a very large range, from < 500 ppm to about 90 000 ppm. Comparing the dissolution rates of terpene lactones and flavone glycosides within the single products, most were approximately the same. Thus, terpene lactones and flavone glycosides were released from these products and dissolved at the same rate in most cases. Furthermore, most of the products investigated released more than the required 75% of the content of both components within 30 min. However, several products showed clear and relevant differences in dissolution rates to the rest (e.g. < 75% within 30 min or even less than 25% after 60 min in one case, indicating much poorer pharmaceutical quality). Beside the comparability respectively standardisation of the extracts used, the in-vitro dissolution of the relevant constituents should be similar to other drugs to guarantee comparable in-vivo performance of herbal products. An important step in standardising pharmaceutical quality is the pharmacopoeial monograph for Ginkgo biloba extract in Germany, standardising the content of pharmacologically relevant substances (flavone glycosides 22–27% and terpen-lactones 5–7%, 2.8-3.4% ginkgolides A, B, C and 2.6-3.2% bilobalide thereof). Many of the investigated products, which refer to the German Commission E (of the Federal Institute for Drugs and Medicinal Devices) monograph, are not in accordance with this specification. Thus, they can not be considered to be pharmaceutically equivalent.
Mechanism of the vasodilator effect of 12-O-methylcurine in rat aortic rings
Authors: Guedes Diego N , Barbosa-Filho José M , Lemos Virgínia S , Côrtes Steyner F
Published: October 2002

The vasodilator effects of 12-O-methylcurine (OMC), a bisbenzylisoquinoline alkaloid isolated from Chondrodendron platyphyllum (Menispermaceae), and its respective mechanism of action were investigated in rat aorta. In either endothelium-intact or endothelium-denuded aortic rings, OMC induced concentration-dependent relaxation in vessels pre-contracted with 0.1μM phenylephrine (IC50 = 63.2 ± 8.8 μM and 73.9 ± 5.3 μM, respectively), 100 μM 5-hydroxy-tryptamine (IC50 = 49.6 ± 13 μM and 49.9±10μM, respectively) and 50 mM KCl (IC50 = 19.9 ± 6.8 μM and 21.1 ± 4.5 μM, respectively). OMC also inhibited in a concentration-dependent and non-competitive manner the concentration-response curves induced by CaCl2 in high K+ (IC50 = 16.7 ± 1.6 μM). In addition, OMC (100 μM) strongly inhibited phenylephrine-induced contractions dependent on calcium influx in the absence and presence of nifedipine (10 μM). In Ca2+-free medium, the transient contractions induced by phenylephrine (0.1 μM) were strongly inhibited by OMC (100 μM), whereas those induced by caffeine (20 mM) were not altered. H-89 (1 μM) and Rp-8-pCPT-cGMPs(3 μM), selective inhibitors of protein kinase A and G, respectively, did not change the relaxant effect of OMC in aortic rings pre-contracted with phenylephrine. Finally, OMC induced a concentration-dependent relaxation (IC50 = 62.8 ± 12.5 μM) of the sustained contractions induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate in normal, but not in Ca2+-free, solution. The above results suggest that OMC induces a vasodilator effect in rat aortic rings by a mechanism independent of the presence of functional endothelium and dependent on the influx of calcium ions through voltage- and receptor-operated calcium channels. Furthermore, it can also be suggested that the inhibition of calcium influx activated by protein kinase C is involved in the vasodilator effect of OMC.
In-vitro release of fluoropyrimidines from PLGA film implants
Authors: Dorta M Jesús , Oliva Alexis , Munguía Obdulia , Llabrés Matías , Fariña José B
Published: October 2002

The release of two low-molecular weight water-soluble fluoropyrimidines, 5-fluorouracil and 5-fluorouridine, from implants of PLGA films was modulated by varying the area (diameter) and number of layers of film per implant. The aim was to achieve continuous release without burst effect for at least a month. The film implants were prepared by the solvent evaporation technique. Except with 5-fluorouracil films, the in-vitro release profiles were in all cases triphasic, indicating that release proceeds by a combination of diffusion and polymer erosion. The experimental data fit the equation resulting from the sum of two exponentials, one direct and the other inverse. 5-fluorouridine release from simple films presented a relatively minor burst effect (24–28%). In contrast, the delivery of both compounds from sandwich-type implants occurred continuously without a burst effect, and lasted for 17–20 days. During the first phase, both 3- and 5-mm sandwiches released 55% of the dose of 5-fluorouridine, at rate constants of 0.037 ± 0.021 h−1 (n = 3) and 0.009±0.003 h−1 (n = 3), respectively. In the second phase, release was gradual from both simple Alms (k2 = 0.011-0.015 h−1) and sandwiches (k2 = 0.018-0.058 h−1). According to the analysis-of-variance results, neither the area nor type of implant influenced the rate constants significantly. The release profiles of 5-fluorouracil from simple films showed a severe burst effect (64–71%). Release of 5-fluorouracil was gradual only from sandwiches, 5 mm in diameter, showing a lag time unobserved in the 3-mm sandwiches. In the second phase, release was gradual (k2 = 0.014 ± 0.003 h−1) from 3-mm implants. However, the high variability in results for 5-mm implants prevents conclusions being drawn about the model parameters. Therefore, the sandwichtype film implants showed their utility for releasing water-soluble drugs for a prolonged time, without burst effect.
Introduction of poly-L-lactic acid microspheres into the skin using supersonic flow: effects of helium gas pressure, particle size and microparticle dose on the amount introduced into hairless rat skin
Authors: Uchida Masaki , Jin Yi , Natsume Hideshi , Kobayashi Daisuke , Sugibayashi Kenji , Morimoto Yasunori
Published: October 2002

A micro particulate bombardment system loaded with DNA- and RNA-coated gold and tungsten micro particles (diameter 1–3 μm; density about 19 g cm−3), the Helios gene gun system (Helios gun system), has been used to deliver a gene into cells by accelerating the micro particles to high velocity using a supersonic flow of helium gas. To investigate whether drug-loaded microspheres, > 20 μm in diameter and about 1.0 g cm−3 in density, could be delivered in powder form quantitatively into the skin using the Helios gun system equipped with a cartridge container fitted with a rupture membrane, we investigated the effect of the helium gas pressure in accelerating indometacin-loaded poly-L-lactic acid (PLA) microspheres, as well as the particle size and the bombardment dose on delivery into the skin. Introduction of indometacin (i.e. indometacin-loaded PLA microspheres) after bombardment, with 3.0 mg indometacin-loaded PLA microspheres of a particle size of 20–38, 44–53 and 75–100 μM at a helium pressure of 100, 200 and 300 psi, of the abdomen of hairless rats increased in parallel with the helium pressure and it was also affected by the particle size, being highest at a diameter of 75–100 μm. However, introduction of higher amounts of PLA microspheres resulted in more severe skin erythema (skin damage) as monitored by the Draize score. Using lower bombardment doses (0.5 and 1.0 mg), the efficiency of introduction was improved and the skin damage markedly reduced. Moreover, discrete bombardment with a low dose provided a more efficient introduction of indometacin and less skin damage. These results suggest that bombardment injection of drug-loaded microspheres in a powdered form by the Helios gun system appears to be a very useful tool for the quantitative delivery of a variety of drugs and an alternative to parenteral injection by needle, especially for delivering water-soluble macromolecules.
Effect of dietary fatty acids on the intestinal permeability of marker drug compounds in excised rat jejunum
Authors: Vine D F , Charman S A , Gibson P R , Sinclair A J , Porter C J H
Published: October 2002

The aim of this study was to explore the effects of diets containing saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and ω-3 and ω-6 polyunsaturated fatty acids (ω-3 and ω-6 PUFA, respectively) on the passive and active transport properties of rat jejunum using marker compounds. Rats were fed diets supplemented with 18.4% (w/w) lipid (4 groups) or standard rat chow (1 group) for a period of 30 days. At the end of the dietary period, mucosal scrapings were taken for the determination of membrane phospholipids, and the apparent jejunal permeability of radiolabelled marker compounds was determined using modified Ussing chambers. Changes in the phospholipid content of the brush border membrane reflected the different lipid content of the diets. The passive paracellular permeability of mannitol was not significantly affected by the fatty acid composition of the diet, although there was a trend toward decreased mannitol permeability in the rats fed both the ω-3 and ω-6 PUFA diets. In comparison, the transcellular diffusion of diazepam was reduced by 20% (P < 0.05) in rats fed diets supplemented with ω-3 and ω-6 PUFA. In the lipid-fed rats, the serosal to mucosal flux of digoxin, an intestinal P-glycoprotein substrate, was reduced by 20% (P < 0.05) relative to the chow-fed group, however there were no significant differences between the different lipid groups. The active absorption of D-glucose via the Na+-dependent transport pathway was highest in the SFA, MUFA and PUFA ω-3 dietary groups, intermediate in the low-fat chow group and lowest in the PUFA ω-6 group, and was positively correlated with short-circuit current. These studies indicate that dietary fatty acid changes can result in moderate changes to the active and passive transport properties of excised rat jejunum.
Selective and sustained occupancy of prostatic α1-adrenoceptors by oral administration of KMD-3213 and its plasma concentration in rats
Authors: Okura T , Yamada S , Abe Y , Kimura R
Published: October 2002

This study examined the ex-vivo occupancy by KMD-3213 of α1-adrenoceptors in the prostate and other tissues of rats in terms of tissue selectivity and duration of occupancy in relation to plasma concentration. Oral administration of KMD-3213 (0.2–20.2μmol kg−1, 0.5 h) dose-dependently decreased [3H]prazosin binding sites (Bmax) in the prostate (42–74%) and submaxillary gland (54–88%) compared with the control value. In contrast, there was only a slight change in the Bmax values in the spleen and cerebral cortex of KMD-3213-treatedrats. The α1-adrenoceptor occupancy in the prostate and submaxillary gland was increased, with plasma free concentration of KMD-3213 at 0.5 h after oral administration of KMD-3213 (0.6–20.2 μ mol kg−1). The receptor occupancy in these tissues was much greater than that in the spleen, heart or cerebral cortex. After oral administration of KMD-3213 (6.1 μ mol kg−1), the α1-adrenoceptor occupancy in the prostate and submaxillary gland occurred rapidly, in parallel with the rise in the plasma concentration of the drug, and it lasted for at least 24 h, despite a remarkable decrease in the plasma concentration. It is concluded that KMD-3213 may produce fairly selective and sustained occupancy of α1-adrenoceptors in the prostate, a target organ for treatment of bladder outlet obstruction in patients with benign prostatic hyperplasia.
Time dependent analysis of multivariate marked renewal processes
Authors: Dshalalow Jewgeni H.
Published: October 2002

The paper examines multivariate delayed marked renewal processes, of which one component is formed by a delayed compound Poisson process observed at epochs of some point process. In addition, the values of these observations (and other components) are watched when crossing their respective thresholds and the value of the original Poisson process at any moment of time, past the first passage time, is the objective of this investigation. The results (which are imperative for classes of semiregenerative processes) are given in closed analytical forms and illustrated on various stochastic models.
A note on stochastic comparisons of excess lifetimes of renewal processes
Authors: Belzunce Félix , Ortega Eva M. , Ruiz José M.
Published: October 2002

In this paper we provide new results about stochastic comparisons of the excess lifetime at different times of a renewal process when the interarrival times belong to several ageing classes. We also provide a preservation result for the new better than used in the Laplace transform order ageing class for series systems.
A reconsideration of Lotka's extinction probability using a bisexual branching process
Authors: Hull David M.
Published: October 2002

It is generally recognized that Alfred Lotka made the first application of
standard Galton-Watson branching process theory to calculate an extinction probability in a specific population (using asexual reproduction). This note applies bisexual Galton-Watson branching process theory to the calculation of an extinction probability from Lotka's data, yielding a somewhat higher value.
Differentiability and monotonicity of expected passage time in Euclidean first-passage percolation
Authors: Howard C. Douglas
Published: October 2002

In first-passage percolation (FPP) models, the passage time Tℓ from the origin to the point ℓeℓ satisfies f(ℓ) := ETℓ = μℓ + o(ℓ½+ε), where μ ∊ (0,∞) denotes the time constant. Yet, for lattice FPP, it is not known rigorously that f(ℓ) is eventually monotonically increasing. Here, for the Poisson-based Euclidean FPP of Howard and Newman (Prob. Theory Relat. Fields108 (1997), 153–170), we prove an explicit formula for f′(ℓ). In all dimensions, for certain values of the model's only parameter we have f′(ℓ) ≥ C > 0 for large ℓ.
Testing for long memory in the presence of a general trend
Authors: Giraitis Liudas , Kokoszka Piotr , Leipus Remigijus
Published: October 2002

The paper studies the impact of a broadly understood trend, which includes a change point in mean and monotonic trends studied by Bhattacharyaet al.(1983), on the asymptotic behaviour of a class of tests designed to detect long memory in a stationary sequence. Our results pertain to a family of tests which are similar to Lo's (1991) modifiedR/Stest. We show that both long memory and nonstationarity (presence of trend or change points) can lead to rejection of the null hypothesis of short memory, so that further testing is needed to discriminate between long memory and some forms of nonstationarity. We provide quantitative description of trends which do or do not fool theR/S-type long memory tests. We show, in particular, that a shift in mean of a magnitude larger thanN-½, whereNis the sample size, affects the asymptotic size of the tests, whereas smaller shifts do not do so.
A probabilistic method for Navier-Stokes vortices
Authors: He Xinyu
Published: October 2002

Consider a Navier-Stokes incompressible turbulent fluid in R2. Let x(t) denote the position coordinate of a moving vortex with initial circulation Γ0 > 0 in the fluid, subject to a force F. Define x(t) as a stochastic process with continuous sample paths described by a stochastic differential equation. Assuming a suitable notion of weak rotationality, it is shown that the stochastic equation is equivalent to a linear partial differential equation for the complex function ψ, i∂ψ/∂t = [-Γ0Δ + F] ψ, where |ψ|2 = ρ(x,t), ρ being the probability density function of finding the vortex centre in position x at time t.
Optimal estimation of diffusion processes hidden by general obstacles
Authors: Kim Hyung Geun , Nam Dougu
Published: October 2002

Let Xt be an n-dimensional diffusion process and S(t) be a set-valued function. Suppose Xt is invisible when it is hidden by S(t), but we can see the process exactly otherwise. In this paper, we derive the optimal estimator E[f(X1) | Xs1Xs∉S(s), 0 ≤ s ≤ 1] for a bounded Borel function f. We illustrate some computations for Gauss-Markov processes.
The growth of general population-size-dependent branching processes year by year
Authors: Jagers Peter , Sagitov Serik
Published: October 2002

We study discrete-time population models where the nearest future of an individual may depend on the individual's life-stage (age and reproduction history) and the current population size. A criterion is given for whether there is a positive probability that the population survives forever. We identify the cases when population size grows exponentially and linearly and show that in the latter population size scaled by time is asymptotically Γ-distributed.
Stochastic differential portfolio games
Authors: Browne Sid
Published: October 2002

We study stochastic dynamic investment games in continuous time between two investors (players) who have available two different, but possibly correlated, investment opportunities. There is a single payoff function which depends on both investors’ wealth processes. One player chooses a dynamic portfolio strategy in order to maximize this expected payoff, while his opponent is simultaneously choosing a dynamic portfolio strategy so as to minimize the same quantity. This leads to a stochastic differential game with controlled drift and variance. For the most part, we consider games with payoffs that depend on the achievement of relative performance goals and/or shortfalls. We provide conditions under which a game with a general payoff function has an achievable value, and give an explicit representation for the value and resulting equilibrium portfolio strategies in that case. It is shown that non-perfect correlation is required to rule out trivial solutions. We then use this general result explicitly to solve a variety of specific games. For example, we solve a probability maximizing game, where each investor is trying to maximize the probability of beating the other's return by a given predetermined percentage. We also consider objectives related to the minimization or maximization of the expected time until one investor's return beats the other investor's return by a given percentage. Our results allow a new interpretation of the market price of risk in a Black-Scholes world. Games with discounting are also discussed, as are games of fixed duration related to utility maximization.
Rates of convergence of stochastically monotone and continuous time Markov models
Authors: Roberts G. O. , Tweedie R. L.
Published: October 2002

In this paper we give bounds on the total variation distance from convergence of a continuous time positive recurrent Markov process on an arbitrary state space, based on Foster-Lyapunov drift and minorisation conditions. Considerably improved bounds are given in the stochastically monotone case, for both discrete and continuous time models, even in the absence of a reachable minimal element. These results are applied to storage models and to diffusion processes.
On the behaviour of a long cascade of linear reservoirs
Authors: Glynn John E. , Glynn Peter W.
Published: October 2002

This paper describes the limiting asymptotic behaviour of a long cascade of linear reservoirs fed by stationary inflows into the first reservoir. We show that the storage in thenth reservoir becomes asymptotically deterministic asn→ ∞, and establish a central limit theorem for the random fluctuations about the deterministic approximation. In addition, we prove a large deviations theorem that provides precise logarithmic asymptotics for the tail probabilities associated with the storage in thenth reservoir whennis large.
Stochastic analysis of partitioning algorithms for matching problems
Authors: Rüschendorf Ludger , Sachs Gernot
Published: October 2002

Partitioning algorithms for the Euclidean matching and for the semi-matching problem in the plane are introduced and analysed. The algorithms are analogues of Karp's well-known dissection algorithm for the travelling salesman problem. The algorithms are proved to run in time nlogn and to approximate the optimal matching in the probabilistic sense. The analysis is based on the techniques developed in Karp (1977) and on the limit theorem of Redmond and Yukich (1993) for quasiadditive functionals.
Convergence to stationarity in the Moran model
Authors: Donnelly Peter , Rodrigues Eliane R.
Published: October 2002

Consider a population of fixed size consisting of N haploid individuals. Assume that this population evolves according to the two-allele neutral Moran model in mathematical genetics. Denote the two alleles by A1 and A2. Allow mutation from one type to another and let 0 < γ < 1 be the sum of mutation probabilities. All the information about the population is recorded by the Markov chain X = (X(t))t≥0 which counts the number of individuals of type A1. In this paper we study the time taken for the population to ‘reach’ stationarity (in the sense of separation and total variation distances) when initially all individuals are of one type. We show that after t∗ = Nγ-1logN + cN the separation distance between the law of X(t∗) and its stationary distribution converges to 1 - exp(-γe-γc) as N → ∞. For the total variation distance an asymptotic upper bound is obtained. The results depend on a particular duality, and couplings, between X and a genealogical process known as the lines of descent process.
Smoothing effect of the superposition of homogeneous sources in tandem networks
Authors: Hordijk Arie , Liu Zhen , Towsley Don
Published: October 2002

We analyze the smoothing effect of superposing homogeneous sources in a network. We consider a tandem queueing network representing the nodes that customers generated by these sources pass through. The servers in the tandem queues have different time varying service rates. In between the tandem queues there are propagation delays. We show that for arbitrary arrival and service processes which are mutually independent, the sum of unfinished works in the tandem queues is monotone in the number of homogeneous sources in the increasing convex order sense, provided the total intensity of the foreground traffic is constant. The results hold for both fluid and discrete traffic models.
Lower bounds for point-to-point wandering exponents in Euclidean first-passage percolation
Authors: Howard C. Douglas
Published: October 2002

In first-passage percolation models, the passage time T(0,L) from the origin to a point L is expected to exhibit deviations of order |L|χ from its mean, while minimizing paths are expected to exhibit fluctuations of order |L|ξ away from the straight line segment . Here, for Euclidean models in dimension d, we establish the lower bounds ξ ≥ 1/(d+1) and χ ≥(1-(d-1)ξ)/2. Combining this latter bound with the known upper bound ξ ≤ 3/4 yields that χ ≥ 1/8 for d=2.
Convergence of Markov chains in the relative supremum norm
Authors: Holden Lars
Published: October 2002

It is proved that the strong Doeblin condition (i.e., ps(x,y) ≥ asπ(y) for all x,y in the state space) implies convergence in the relative supremum norm for a general Markov chain. The convergence is geometric with rate (1 - as)1/s. If the detailed balance condition and a weak continuity condition are satisfied, then the strong Doeblin condition is equivalent to convergence in the relative supremum norm. Convergence in other norms under weaker assumptions is proved. The results give qualitative understanding of the convergence.
On the behaviour of some new ageing properties based upon the residual life of k-out-of-n systems
Authors: Li Xiaohu , Zuo Ming J.
Published: October 2002

In this paper, we investigate k-out-of-n systems with independent and identically distributed components. Some characterizations of the IFR(2), DMRL, NBU(2) and NBUC classes of life distributions are obtained in terms of the monotonicity of the residual life given that the (n-k)th failure has occurred at time t ≥ 0. These results complement those reported by Belzunce, Franco and Ruiz (1999). Similar conclusions based on the residual life of a parallel system conditioned by the (n-k)th failure time are presented as well.
The travel time in carousel systems under the nearest item heuristic
Authors: Litvak Nelly , Adan Ivo
Published: October 2002

A carousel is an automated warehousing system consisting of a large number of drawers rotating in a closed loop. In this paper, we study the travel time needed to pick a list of items when the carousel operates under the nearest item heuristic. We find a closed form expression for the distribution and all moments of the travel time. We also analyse the asymptotic behaviour of the travel time when the number of items tends to infinity. All results follow from probabilistic arguments based on properties of uniform order statistics.
The size order of the state vector of discrete-time homogeneous Markov systems
Authors: Kipouridis I. , Tsaklidis G.
Published: October 2002

The size order problem of the probability state vector elements of a homogeneous Markov system is examined. The time t0 is evaluated, after which the order of the state vector probabilities remains unchanged, and a formula to quickly find a lower bound for t0 is given. A formula for approximating the mode of the state sizes ni(t) as a function of the means Eni(t), and a relation to evaluate P(ni(t) = x+1) by means of certain terms which constitute P(ni(t) = x) are derived.
Genetic loci for pathological myopia are not associated with juvenile myopia
Authors: Mutti Donald O. , Semina Elena , Marazita Mary , Cooper Margaret , Murray Jeffrey C. , Zadnik Karla
Published: October 2002

The purpose of this study was to evaluate chromosomal regions previously linked to pathological myopia for linkage to juvenile myopia in a sample of myopic children and their families. Of 125 families with a myopic child participating in the Orinda longitudinal study of myopia, 53 submitted 221 buccal swab samples for genetic analysis. Myopia in proband children was defined as −0.75 D or more myopia in both meridians on cycloplegic autorefraction (1% tropicamide). Affected status in parents and siblings was obtained by survey. DNA was extracted from buccal mucosal cells, amplified by polymerase chain reaction (PCR), and then analyzed with seven markers for chromosome 12 and five markers for chromosome 18 in the regions previously associated with pathological myopia. LOD scores were not significant for any marker tested. The largest positive LOD score was 0.15 for GATA30F04. Model‐free methods using a SimIBD approach suggested a possible linkage at one marker, GATA6H09 (P = 0.003), but these results were not supported by transmission disequilibrium test (TDT) analysis. The statistical power to detect LOD scores of ≥1.0, assuming homogeneity, was estimated at 93.2%. We found no confirmatory evidence of linkage between juvenile myopia and regions of chromosomes 12 and 18 previously associated with pathological myopia. © 2002 Wiley‐Liss, Inc.
Real‐time quantitation of hepatitis B virus (HBV) DNA in tumorous and surrounding tissue from patients with hepatocellular carcinoma
Authors: Zanella Isabella , Rossini Angelo , Domenighini Daniela , Albertini Alberto , Cariani Elisabetta
Published: October 2002

Few data are available on the levels of HBV DNA in liver tissue of patients with hepatocellular carcinoma. In this study, HBV DNA was quantitated by a TaqMan real‐time PCR method and results were normalised to an endogenous reference gene. The assay could detect reproducibly viral sequences from over 107 to less than 50 copies/μg of liver DNA. The HBV DNA content in liver samples from 11 HBsAg‐positive patients (median: 105 copies/μg of DNA) was significantly higher (P < 0.001) compared to the viral DNA concentration detected in liver samples from 15 of 25 HBsAg‐negative patients (median: 2.6 × 102 copies/μg). A liver DNA amount ≥1 HBV DNA copy per cell was detected in half of tissue samples from HBsAg‐positive patients, and in none from HBsAg‐negative ones. Liver tissue HBV DNA content was significantly higher in anti‐HCV‐negative than in anti‐HCV‐positive cases (P < 0.001). These results show that the quantitation of liver HBV DNA by real‐time PCR can be useful to understand HBV state in hepatocellular carcinoma and viral interplay in patients with multiple viral infections. J. Med. Virol. 68:494–499, 2002. © 2002 Wiley‐Liss, Inc.
Multiculturalism, universalism, and science education: In search of common ground
Authors: Siegel Harvey
Published: October 2002

Multiculturalism's proper place in science education has been the subject of considerable controversy in the recent science education literature. It is the theme of a recent symposium in this journal, which raises and treats a wide range of issues with important ramifications for science education. A key issue—and the one on which I focus—is whether (and if so to what extent) a multicultural approach to science education is compatible with a “universalist” conception of science. My main aim is to show that there is actually much more agreement between “universalists” and multicultural “localists” concerning that compatibility than might be apparent at first glance. A second aim is to defend the former from criticisms made in the symposium papers. I first attempt to make clear what “universalism” does, and does not, involve. I then explore the justification of multicultural science education, and suggest both that that justification is moral (rather than epistemological) in nature; and that if science education is indeed obliged to embrace multiculturalism, that obligation must itself be understood to be a culturally transcendent one. Finally, I address several curricular issues treated in the symposium papers. The overall conclusion is that the most defensible conception of science education is one in which it is conceived to be both multicultural and universal. © 2002 Wiley Periodicals, Inc. Sci Ed 86:803–820, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.1052
Designing production planning and control systems
Authors: Van Dierdonck Roland , Miller Jeffrey G.
Published: October 2002

This paper presents a contingency model designed to explain aggregate differences in the specifications for production planning and control systems across firms. The specifications for a firm's system, stated broadly in terms of the investment in information processing systems and organizational integrativeness, are related to that firm's competitive strategy and environment. An analysis of data from a limited sample of companies, and a panel of managers, provides insights into the applicability of the concepts used in the model, and its potential usefulness.
The effect of inventory costs on the LIFO layer liquidation decision
Authors: Cottell Philip G. , Patton Jon M.
Published: October 2002

Due to double digit inflation during the latter part of the past decade, many companies have switched to the LIFO method of inventory valuation. LIFO layer liquidation occurs whenever a company which uses the LIFO inventory valuation method decides to reduce ending inventory to a level below beginning inventory. During inflationary periods, a company that allows this liquidation to occur will have to pay higher federal income taxes. This paper develops a decision rule of whether or not management should make a special purchase to avoid LIFO layer liquidation.

The tradeoffs involved with this special purchase are reduced federal income taxes coupled with higher carrying costs and order or setup costs. Since some carrying costs are tax deductible and some are not, most of the carrying costs are considered individually in developing the decision model.

The tax deductible costs that are considered are the cost of capital, property tax, insurance costs, handling costs, and warehouse costs. The carrying costs considered that are not tax deductible are the risk or probability of deterioration and obsolescence.

Since the costs and tax payment occur at different points in time, the present value of each of these transactions are made for comparison purposes. The decision rule is based on a comparison between the present value of these costs and the present value of the cost of a LIFO layer liquidation. An example is then used to illustrate the decision rule.
Service levels for priority and nonpriority products with a common component
Authors: Adlakha Veena , Singhal Kalyan
Published: October 2002

This paper refers to an article by Baker, recently published in the Journal of Operations Management. We point out an error, and provide correction, in the calculation of service level for a non priority product when a priority product and the nonpriority product share a common component.