bluuebunny/crossref_metadata_2025 huggingface dataset:
Tie channel sedimentation rates, oxbow formation age and channel migration rate from optically stimulated luminescence (OSL) analysis of floodplain deposits
Authors: Rowland Joel C. , Lepper Kenneth , Dietrich William E. , Wilson Cathy J. , Sheldon R.
Published: August 2005

Using optically stimulated luminescence (OSL) analysis we obtained depositional ages ranging from 25 ± 10 to 928 ± 144 years before present for sediments deposited in oxbow lakes along three lowland river systems. The dated sediments were collected from the banks of tie channels along the Lower Mississippi River, the Fly River in Papua New Guinea, and Birch Creek along the Yukon River in Alaska. Tie channels connect the oxbow lakes to the main stem river and allow the exchange of water and suspended sediment between the two. The banks consist of fine sand and sandy silt beds interlayered with silt and clay. OSL samples were collected both horizontally from exposed banks and vertically by coring through levee crests; sample collection was targeted at beds containing appreciable quantities of fine sand. OSL ages were determined using single‐grain or in some cases single‐aliquot techniques and dose distribution analysis. Samples were first collected along the Lower Mississippi tie channel to compare OSL dates with historical data sources and test the applicability of OSL in these settings; the OSL dates agreed closely with historical data. In all three river systems, OSL dating allowed the determination of vertical accretion rates, tie channel advancement rates, and oxbow lake ages. In Papua New Guinea, OSL sampling also provides an estimate of lateral migration rates of the Fly River and allows a comparison of modern mineinfluenced deposition rates with natural background rates over the last 1000 years. Results from Papua New Guinea and the Mississippi River suggest that the advancement rate of tie channels responds directly to changes in the sediment load of the main stem river. Copyright © 2005 John Wiley & Sons, Ltd.
Assessing household health expenditure with Box–Cox censoring models
Authors: Chaze Jean‐Paul
Published: August 2005

In order to assess the combined presence of zero expenditures and a heavily skewed distribution of positive expenditures, the Box–Cox transformation with location parameter is used to define a set of models generalising the standard Tobit, Heckman selection and double‐hurdle models. Extended flexibility with respect to previous specifications is introduced, notably regarding negative transformation parameters, which may prove necessary for medical expenditures, and corner‐solution outcomes. An illustration is provided by the analysis of household health expenditure in Switzerland. Copyright © 2005 John Wiley & Sons, Ltd.
A dynamic analysis of disability and labour force participation in Ireland 1995–2000
Authors: Gannon Brenda
Published: August 2005

This paper aims to analyse the effect of disability on participation in the labour force, using the Irish component of the European Community Household Panel Survey 1995–2000. A range of panel models are considered, but to allow for any unobserved influences or state dependence in labour force participation, our preferred model is a dynamic panel model. We show how the estimates of current disability are changed once we control for the effect of past disability and previous participation. We compare base estimates of disability with those controlling for unobserved heterogeneity and past participation. The results suggest that the base effect of disability is overestimated by between 40–60% for men and by 5–10% for women. Copyright © 2005 John Wiley & Sons, Ltd.
Utilization of public health centres in Portugal: effect of time costs and other determinants. Finite mixture models applied to truncated samples
Authors: Lourenço Óscar D. , Ferreira Pedro L.
Published: August 2005

The impact of time costs on the utilization of medical care has been a subject of theoretical and empirical research since the early 1970s.

The main goal of this paper is to show the effect of time costs on the number of visits to general practitioners (GP) in Portuguese public health centres. We measured the elasticity of primary health care utilization relative to the total time spent in the health centre and relative to travel time. We also provided evidence regarding the impact of an appointment delay on the utilization of public GP services.

Our data resulted from the application of an endogenous sampling scheme, resulting in a truncated‐at‐zero data set. To model our dependent variable, number of visits, and accounting for the truncated nature of the data we used a finite mixture model specification.

The data were obtained from the most recent implementation in Portugal of the 2003/2004 Europep Survey.

The two‐component negative binomial II finite mixture model led to the identification of two different latent classes of health centre users: a low‐users class that comprises 88% of patients with an estimated utilization mean of 4.3 GP visits per year and a frequent‐users class with an estimated utilization mean of 11.1 visits for the remaining 12% of the population.

We failed to find any statistically significant elasticity of time cost utilization, when this variable is measured as the total time spent in the health centre. Regarding the effect of an appointment delay on health centre utilization we concluded that individuals respond to this variable by lowering the number of GP visits. This last finding may have policy implications, which will be discussed at the end of the paper. Copyright © 2005 John Wiley & Sons, Ltd.
Latent class models for use of primary care: evidence from a British panel
Authors: Bago d'Uva Teresa
Published: August 2005

This paper models access to and utilisation of primary care using data from the British Household Panel Survey for the period 1991–2001. A latent class panel data framework is adopted to model individual unobserved heterogeneity in a flexible way. Accounting for the panel structure of the data leads to a substantial improvement in fit, and permits the identification of latent classes of users of health care. Analysis by gender shows that men and women respond differently to some factors, in particular, to age and income. There is evidence of a positive impact of income on the probability of seeking primary care. This effect is especially significant in the case of women. For both genders, the marginal effect of income on the propensity to visit a GP is greater for individuals who are less likely to seek primary care. A latent class aggregated count data model for the number of GP visits classifies individuals in three latent classes and shows a positive income effect particularly amongst those with lower levels of utilisation. Copyright © 2005 John Wiley & Sons, Ltd.
Effect of morphology and discharge on hyporheic exchange flows in two small streams in the Cascade Mountains of Oregon, USA
Authors: Wondzell Steven M.
Published: August 2005

Stream‐tracer injections were used to examine the effect of channel morphology and changing stream discharge on hyporheic exchange flows. Direct observations were made from well networks to follow tracer movement through the hyporheic zone. The reach‐integrated influence of hyporheic exchange was evaluated using the transient storage model (TSM) OTIS‐P. Transient storage modelling results were compared with direct observations to evaluate the reliability of the TSM. Results from the tracer injection in the bedrock reach supported the assumption that most transient storage in headwater mountain streams results from hyporheic exchange. Direct observations from the well networks in colluvial reaches showed that subsurface flow paths tended to parallel the valley axis. Cross‐valley gradients were weak except near steps, where vertical and cross‐valley hydraulic gradients indicated a strong potential for stream water to downwell into the hyporheic zone. The TSM parameters showed that both size and residence time of transient storage were greater in reaches with a few large log‐jam‐formed steps than in reaches with more frequent, but smaller steps. Direct observations showed that residence times in the unconstrained stream were longer than in the constrained stream and that little change occurred in the location and extent of the hyporheic zone between low‐ and high‐baseflow discharges in any of the colluvial reaches. The transient storage modelling results did not agree with these observations, suggesting that the TSM was insensitive to long residence‐time exchange flows and was very sensitive to changes in discharge. Disagreements between direct observations and the transient storage modelling results highlight fundamental problems with the TSM that confound comparisons between the transient storage modelling results for tracer injections conducted under differing flow conditions. Overall, the results showed that hyporheic exchange was little affected by stream discharge (at least over the range of baseflow discharges examined in this study). The results did show that channel morphology controlled development of the hyporheic zone in these steep mountain stream channels. Copyright © 2005 John Wiley & Sons, Ltd.
The effects of spatial configuration on preschoolers' attention strategies, selective attention, and incidental learning
Authors: Blumberg Fran C. , Torenberg Meira
Published: August 2005

This study investigated the effects of spatial arrangement on preschool children's selective attention and incidental learning. Three‐ and four‐year old children were shown a multi‐coloured box designated as a ‘special place’ containing miniature chairs and models of animals. One category of objects were designated as relevant and one as irrelevant. Relevant items were placed in each of the apparatus' corners, in the middle of its walls, or in two corners and in the middle of two walls. Findings revealed that children shown relevant items in corners demonstrated the greatest number of correct relocations for relevant items while those shown relevant items in the middle of the walls showed the greatest number of correct relocations for irrelevant items. Findings also suggest that for both age groups, the ability to recall relevant items may have been independent of their ability to demonstrate a selective attention strategy. Copyright © 2005 John Wiley & Sons, Ltd.
Effects of surface modification of poly (3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) on physicochemical properties and on interactions with MC3T3‐E1 cells
Authors: Li Jing , Yun Huan , Gong Yandao , Zhao Nanming , Zhang Xiufang
Published: August 2005

As a new member of the polyhydroxyalkanoate (PHA) family, poly (3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) has better mechanical and processible properties than poly (3‐hydroxybutyrate) (PHB). Still, it is difficult to introduce functional groups to the polyester carbon chain of PHBHHx, which restricts the modification of PHBHHx for a wide range. In this study, a procedure for the modification of the surface of PHBHHx films under strongly alkaline conditions was described. Through this kind of modification, carboxyl and hydroxyl groups were introduced to the surface and the total surface free energy was increased, which was mainly due to the increased polar components. Meanwhile, this process makes the surface rougher, resulting in larger total surface areas. After mineralization in simulated body fluids (SBFs), the apatite nucleation and growth on the surface‐hydrolyzed PHBHHx films were significantly faster than on the unmodified PHBHHx films. This phenomenon should have a close relationship with the increased carboxyl and hydroxyl groups. The physicochemical properties also influenced the cell response to PHBHHx films. Compared to unmodified PHBHHx, fibronectin adsorption, and MC3T3‐E1 cell attachment and proliferation were significantly greater on surface‐hydrolyzed PHBHHx, which may be due to the increased surface free energy and rougher surface. Therefore, surface hydrolysis makes PHBHHx more suitable for osteoblast cell response and for application in bone‐tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Adhesion molecule expression by osteogenic cells cultured on various biodegradable scaffolds
Authors: Shur I. , Zilberman M. , Benayahu D. , Einav S.
Published: August 2005

Design of tissue‐engineered cell‐loaded device involves cells seeding onto scaffolds in vitro, allowing them to settle and grow before in vivo transplantation. Interaction between scaffold and cells is important in the development of desired tissues. The present study aimed to investigate the effect of cell–polymer interactions on cell morphology and expression of surface markers of osteogenic MBA‐15 cells cultured on various bioresorbable polymers. In this study, we used various polymers: poly(L‐lactic acid) (PLLA), poly(DL‐lactic acid) (PDLLA), poly(L‐lactic‐glycolic acid) (PLGA), and poly(DL‐lactide‐glycolide acid) PDLGA1 and PDLGA2. Expression of integrinα‐M (CD11b), selectin‐E (CD62E), and PECAM‐1 (CD31), important in cell–cell and cell–matrix interactions, were quantified by flow‐cytometry analysis. Cells grown on PDLGA1 films demonstrated fivefold increase in CD62E expression and two‐folds increase in CD11b expression. None of the polymers affected the levels of CD31. Identified differential effect of polymers on the expression of cell‐adhesion molecules by osteoprogenitors in vitro might help to choose optimal parameters for successful engraftment of cell‐loaded constructs. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Development of the uterine shell glands during the preovulatory and early gestation periods in oviparous and viviparous Lacerta vivipara
Authors: Heulin Benoit , Stewart James R. , Surget‐Groba Yann , Bellaud Patricia , Jouan Florence , Lancien Gérard , Deunff Jean
Published: August 2005

The evolutionary process leading to the emergence of viviparity in Squamata consists of lengthening the period of egg retention in utero coupled with marked reduction in the thickness of the eggshell. We used light microscopy and scanning electron microscopy to study uterine structure during the reproductive cycle of oviparous and viviparous females of the reproductively bimodal Lacerta vivipara. We compared the structure of the uterine shell glands, which secrete components of the eggshell, during preovulatory and early gestation phases of the reproductive cycle and also compared histochemistry of the eggshells. The uterine glands of both reproductive forms undergo considerable growth within a period of a few weeks during folliculogenesis and vitellogenesis preceding ovulation. The majority of the proteinaceous fibers of the shell membrane are secreted early in embryonic development and the uterine glands regress shortly thereafter. This supports previous observations indicating that, in Squamata, secretion of the shell membrane occurs very rapidly after ovulation. The most striking differences between reproductive modes were larger uterine glands at late vitellogenesis in oviparous females, 101 μm compared to 60 μm in viviparous females, and greater thickness of the shell membrane during early gestation in oviparous females (52–73 μm) compared to viviparous females (4–8 μm). Our intraspecific comparison supports the conclusions of previous studies that, prior to ovulation, the uterine glandular layer is less developed in viviparous than in oviparous species, and that this is the main factor accounting for differences in the thickness of the shell membrane of the two reproductive forms of squamates. J. Morphol. © 2005 Wiley‐Liss, Inc.
Ultrastructural evidence for secretion from the epithelium of ampulla ductus deferentis of the fan‐throated lizard Sitana ponticeriana Cuvier
Authors: Akbarsha M.A. , Tamilarasan V. , Kadalmani B. , Daisy P.
Published: August 2005

Among reptiles, an ampulla ductus deferentis has been reported only in Squamata. Fairly detailed studies are available only for two species, the lizard Calotes versicolor (Fam: Agamidae) and the snake Seminatrix pygaea (Fam: Colubridae). The light microscopic study on C. versicolor revealed the ampulla to be a prominent organ, whereas the light and transmission electron microscopic study in S. pygaea revealed it to be discernable only in histological preparations. Further, the epithelium of the ductal portion of vas deferens as well as the ampulla of C. versicolor appears to contribute to the seminal plasma and can also phagocytose dead sperm, whereas in S. pygaea neither of these roles has been established. Thus, we hypothesize that there may be variations in the anatomy, histology, and the role of the vas deferens in general, and the ampulla in particular, of the squamate reptiles. In this study, the ductus deferens of the small fan‐throated lizard Sitana ponticeriana (Fam: Agamidae) was subjected to light and transmission electron microscopic analysis. In this lizard the ampulla is more prominent than in C. versicolor. The epithelium of the ductal portion of vas deferens consists of principal cells (with features reflecting roles in endocytosis and phagocytosis of dead sperm), dark cells (which are absent in the epithelium of the ductal portion of vas deferens of snakes), and basal cells. The ampulla of S. ponticeriana is differentiated into storage and glandular portions. The epithelium of the storage portion is like that in the ductal portion of the vas deferens, whereas that of the glandular portion, consisting of dark and light principal cells and foamy cells, is tall and forms into smooth villous folds. All three cell types show evidence for a role in secretion, in all likelihood different from each other, for release into the lumen to contribute to seminal plasma. These cells do not provide evidence of a role in phagocytosis of dead sperm. It appears that within the Squamata, the ductal ampulla differs in structure as well as function. We suggest that the ductal ampulla of agamid lizards is a composite gland of the ampulla ductus deferentis and seminal vesicles of mammals. J. Morphol. © 2005 Wiley‐Liss, Inc.
Validated method for determination of bromopride in human plasma by liquid chromatography–electrospray tandem mass spectrometry: application to the bioequivalence study
Authors: Nazare P. , Massaroti P. , Duarte L. F. , Campos D. R. , Marchioretto M. A. M. , Bernasconi G. , Calafatti S. , Barros F. A. P. , Meurer E. C. , Pedrazzoli J. , Moraes L. A. B.
Published: August 2005

A simple, sensitive and specific liquid chromatography‐tandem mass spectrometry method for the quantification of bromopride I in human plasma is presented. Sample preparation consisted of the addition of procainamide II as the internal standard, liquid‐liquid extraction in alkaline conditions using hexane‐ethyl acetate (1 : 1, v/v) as the extracting solvent, followed by centrifugation, evaporation of the solvent and sample reconstitution in acetonitrile. Both I and II (internal standard, IS) were analyzed using a C18 column and the mobile‐phase acetonitrile‐water (formic acid 0.1%). The eluted compounds were monitored using electrospray tandem mass spectrometry. The analyses were carried out by multiple reaction monitoring (MRM) using the parent‐to‐daughter combinations of m/z 344.20 > 271.00 and m/z 236.30 > 163.10. The areas of peaks from analyte and IS were used for quantification of I. The achieved limit of quantification was 1.0 ng/ml and the assay exhibited a linear dynamic range of 1–100.0 ng/ml and gave a correlation coefficient (r) of 0.995 or better. Validation results on linearity, specificity, accuracy, precision and stability, as well as application to the analysis of samples taken up to 24 h after oral administration of 10 mg of I in healthy volunteers demonstrated the applicability to bioequivalence studies. Copyright © 2005 John Wiley & Sons, Ltd.
LC–nanospray‐MS/MS analysis of hydrophobic proteins from membrane protein complexes isolated by blue‐native electrophoresis
Authors: Fandiño Anabel S. , Rais Isam , Vollmer Martin , Elgass Helmuth , Schägger Hermann , Karas Michael
Published: August 2005

The application of two‐dimensional electrophoresis for the identification of hydrophobic membrane proteins is principally hampered by precipitation of many of these proteins during first‐dimension, isoelectric focusing. Therefore new strategies towards the identification and characterization of membrane proteins are being developed. In this work we present a direct and rapid approach from blue‐native gels to mass spectrometry, which allows the analyses of complete complexes and prevents protein aggregation of hydrophobic regions during electrophoresis. We combine blue‐native gel electrophoresis and liquid chromatography–nanospray‐iontrap tandem mass spectrometry to analyze the composition of oxidative phosphorylation complexes I, III, IV and V from bovine‐heart mitochondria as a model system containing a number of highly hydrophobic proteins. Bands from blue‐native gels were subjected either to in‐gel or to in‐solution tryptic digestion. The obtained peptide mixtures were further analyzed by liquid chromatography–tandem mass spectrometry and the corresponding proteins were identified by database search. From a total of 86 proteins, 67 protein subunits could be identified including all highly hydrophobic components, except the ND4L and ND6 subunits of complex I. We demonstrate that liquid chromatography–tandem mass spectrometry combined to blue‐native electrophoresis is a straightforward tool for proteomic analysis of multiprotein complexes, and especially for the identification of very hydrophobic membrane protein constituents that are not accessible by common isoelectric focusing/sodium dodecyl sulphate gel electrophoresis. Copyright © 2005 John Wiley & Sons, Ltd.
Unambiguous detection of astaxanthin and astaxanthin fatty acid esters in krill (Euphausia superba Dana)
Authors: Grynbaum Marc David , Hentschel Petra , Putzbach Karsten , Rehbein Jens , Krucker Manfred , Nicholson Graeme , Albert Klaus
Published: August 2005

HPLC atmospheric pressure chemical ionization (APCI)/MS, GC MS, HPLC diode array detection (DAD), and NMR were used for the identification of astaxanthin and astaxanthin fatty acid esters in krill (Euphausia superba Dana). Matrix solid phase dispersion was applied for the extraction of the carotenoids. This gentle and expeditious extraction technique for solid and viscous samples leads to distinct higher enrichment rates than the conventional liquid–liquid extraction. The chromatographic separation was achieved employing a C30 RP column that allows the separation of shape‐constrained geometrical isomers. A methanol/tert‐butylmethyl ether/water gradient was applied. (all‐E) Astaxanthin and the geometrical isomers were identified by HPLC APCI/MS, by coelution with isomerized authentical standard, by UV spectroscopy (DAD), and three isomers were unambiguously assigned by microcoil NMR spectroscopy. In this method, microcoils are transversally aligned to the magnetic field and have an increased sensitivity compared to the conventional double‐saddle Helmholtz coils, thus enabling the measurement on small samples. The carotenol fatty acid esters were saponified enzymatically with Lipase type VII from Candida rugosa. The fatty acids were detected by GC MS after transesterification, but also without previous derivatization by HPLC APCI/MS. C14:0, C16:0, C16:1, C18:1, C20:0, C20:5, and C22:6 were found in astaxanthin monoesters and in astaxanthin diesters. (all‐E) Astaxanthin was identified as the main isomer in six fatty acid ester fractions by NMR. Quantitation was carried out by the method of internal standard. (13‐cis) Astaxanthin (70 μg/g), 542 μg/g (all‐E) astaxanthin, 36 μg/g unidentified astaxanthin isomer, 62 μg/g (9‐cis) astaxanthin, and 7842 μg/g astaxanthin fatty acid esters were found.
Chararacterization of a monolithic immobilized trypsin microreactor with on‐line coupling to ESI‐MS
Authors: Křvenková Jana , Bilková Zuzana , Foret František
Published: August 2005

The preparation and characterization of a miniaturized trypsin reactor using on‐line coupling with an ESI‐TOF mass spectrometer are described. L‐1‐Tosylamido‐2‐phenylethyl chloromethyl ketone‐trypsin was covalently immobilized on poly(glycidyl methacrylate‐co‐ethylene dimethacrylate) monolith prepared in a 75 μm ID fused silica capillary resulting in a bioreactor with high local concentration of the proteolytic enzyme. Covalent immobilization of trypsin on this support was performed using the epoxide functional groups in either a one‐ or a multistep reaction. For on‐line protein digestion‐MS analysis the bioreactor was coupled with the mass spectrometer using a liquid junction microelectrospray interface. The performance of the reactor was tested using an on‐line flow through the system with flow rates of 50–300 nL/min. The resulting protein consumption was in the atto‐ to low femtomole range. Proteolytic activity was characterized in a wide range of conditions with respect to the flow rate, pH, and temperature. Complete protein digestion was achieved in less than 30 s at 25°C with the sequence coverage of 80% (cytochrome c), which is comparable to 3 h digestion in solution at 37°C. Besides the good performance at laboratory temperature, the immobilized trypsin in the bioreactor also performed well at lower pH compared to the standard in‐solution protocols.
Synthesis and Properties of Polyelectrolyte Gels with Embedded Voids
Authors: Komarova Galina A. , Starodubtsev Sergey G. , Khokhlov Alexei R.
Published: August 2005

Summary: “Swiss‐cheese” polyelectrolyte gels, i.e., gels containing isolated voids filled with water were synthesized and studied. The gels were obtained by three‐dimensional copolymerization of neutral and charged monomers in the presence of oil/water emulsion stabilized by ionic surfactant. After removal of the surfactant and droplets of oil from the gel, the latter contains voids surrounded with charged swollen polymer network. Experiments were performed with slightly cross‐linked gels of copolymers of sodium‐2‐acrylamide‐2‐methyl‐1‐propanesulfonate with acrylamide. The gel containing voids absorbs much more anionic dyes than the control gel with the same chemical composition of the network obtained in homogeneous solution. This effect is due to strongly inhomogeneous distribution of the low molecular weight anions between the voids and the anionic matrix of the gel. The study of diffusion of the dyes in the gels with and without voids and of the kinetics of their swelling and collapse shows that the voids in the gel are isolated.

Optical micrograph of polyelectrolyte gel with embedded emulsion droplets.

magnified image

Optical micrograph of polyelectrolyte gel with embedded emulsion droplets.
Mass spectrometry and isotopes: A century of research and discussion
Authors: Budzikiewicz Herbert , Grigsby Ronald D.
Published: August 2005

In 1815, the British physician William Prout had advanced the theory that the molecular masses of elements were multiples of the mass of hydrogen. This “whole number rule” (and especially deviations from it) played an important role in the discussion whether elements could be mixtures of isotopes. F. Soddy's discovery (1910) that lead obtained by decay of uranium and of thorium differed in mass was considered a peculiarity of radioactive materials.

The question of the existence of isotopes came up when the instruments developed by J.J. Thomson and by W. Wien to study cathode and canal rays by deflection in electric and magnetic fields were steadily improved. In 1913, Thomson mentioned a weak line at mass 22 accompanying the expected one at mass 20 when he analyzed the mass spectrum of neon. Subsequently Aston obtained the mass spectrum of chlorine with masses at 35 and 37. Still in 1921, Thomson objected heavily to the idea of isotopes.

The isotope problem was finally settled, but more accurate mass measurements showed that even isotopic weights differed to some extent from the whole numbers. Based on earlier ideas of P. Langevin and J.‐L. Costa, F.W. Aston and A.J. Dempster developed the idea of packing fractions and mass defects due to the transformation of a portion of the matter comprising the atomic nucleus into energy.

While the determination of the exact isotopic masses had improved over the years, the accurate determination of isotopic abundances remained a problem as long as photographic recording was used. Here especially A.O. Nier pioneered using dual collectors and compensation measurements. This was the prerequisite for the discovery that isotopic ratios varied somewhat in nature. M. Dole discovered the fractionation of oxygen isotopes by photosynthesis and respiration. Today 13C/12C‐ratios are employed to detect adulterations of food and in doping analysis, and 14C/13C‐ratios obtained by accelerator mass spectrometry are used for dating historical objects, just to give some examples. © 2005 Wiley Periodicals, Inc.
Prevention of levodopa‐induced dyskinesias by a selective NR1A/2B N‐methyl‐D‐aspartate receptor antagonist in parkinsonian monkeys: Implication of preproenkephalin
Authors: Morissette Marc , Dridi Mehdi , Calon Frédéric , Tahar Abdallah Hadj , Meltzer Leonard T. , Bédard Paul J. , Di Paolo Thérèse
Published: August 2005

Enkephalin is reported to play an important role in the pathophysiology of levodopa (LD) ‐induced dyskinesias. The present study investigated the effect of chronic treatment with a selective NR1A/2B N‐methyl‐D‐aspartate (NMDA) receptor antagonist, CI‐1041, on the expression of preproenkephalin‐A (PPE‐A) in brains of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) ‐treated monkeys in relation to the development of LD‐induced dyskinesias. Four MPTP‐monkeys received LD/benserazide alone; they all developed dyskinesias. Four other MPTP‐monkeys received LD/benserazide plus CI‐1041; only one of them developed mild dyskinesias at the end of the fourth week of treatment. Four normal monkeys and four saline‐treated MPTP monkeys were also included. MPTP‐treated monkeys had extensive and similar striatal dopamine denervation. An increase of PPE‐A mRNA levels assayed by in situ hybridization was observed in the lateral putamen (rostral and caudal) and caudate nucleus (rostral) of saline‐treated MPTP monkeys compared to controls, whereas no change or a small increase was observed in their medial parts. Striatal PPE‐A mRNA levels remained elevated in LD‐treated MPTP monkeys, whereas cotreatment with CI‐1041 brought them back to control values. These findings suggest that chronic blockade of striatal NR1A/2B NMDA receptors with CI‐1041 normalizes PPE‐A mRNA expression and prevents the development of LD‐induced dyskinesias in an animal model of Parkinson disease. © 2005 Movement Disorder Society
Entdeckung der Calcium‐Antagonisten: Ein kurzer historischer Rückblick
Authors: Goldmann Siegfried
Published: August 2005

Der Begriff des Ca2+‐Antagonismus wurde in den sechziger Jahren von A. Fleckenstein geprägt. Er wählte diese Bezeichnung für Verbindungen, die die Kontraktion von glatten Muskelpräparaten unterbanden. Zeitgleich wurde von Bossert und Vater (Bayer AG) die Substanzklasse der 1, 4‐Dihydropyridine entdeckt, mit Nifedipin als erstem Produkt, das vor 30 Jahren als Adalat® in den Markt eingeführt wurde. Diese Substanzen erwiesen sich als die wirksamsten Ca2+‐Antagonisten.

Wissenschaftlich trug die Klasse der 1, 4‐Dihydropyridine zur Charakterisierung des spannungsabhängigen Ca2+‐Kanals bei. Eine hochaffine und enantioselektive Bindestelle konnte 1980 identifiziert und die Aminosäuresequenz des Kanalproteins 1986 aufgeklärt werden. Zum größeren Verständnis für die Wirkweise des Ca2+‐Kanals trugen die 1982 entdeckten Ca2+‐Agonisten bei, die sich pharmakologisch genau entgegengesetzt zu den Antagonisten verhielten. Sie steigerten den Ca2+‐Einstrom in die glatte Muskelzelle, waren daher am Herzen positiv inotrop und an den Gefäßen konstringierend und somit blutdrucksteigernd. Ca2+‐Antagonisten binden an den inaktiven Zustand des Ca2+‐Kanals und stabilisieren ihn, wodurch der Ca2+‐Einstrom in die Zelle gesenkt wird. Ca2+‐Agonisten stabilisieren den offenen Zustand des Kanals und erhöhen so den Ca2+‐Ionenstrom in die Zelle.

Mit Hilfe von so genannten Caged‐Ca2+‐Antagonisten konnte gezeigt werden, dass die Hauptmenge der für die Kontraktion wichtigen Ca2+‐Ionen aus dem Extrazellularraum und nicht aus intrazellulären Speichern stammt.
Medizinische Chemie der L‐Typ‐Calcium‐Kanalblocker: Dihydropyridine und Nicht‐Dihydropyridine
Authors: Schubert‐Zsilavecz Manfred , Stark Holger
Published: August 2005

Nach der ersten Beschreibung einer physiologischen Bedeutung von Calciumionen an kardialen Geweben im Jahre 1883 von Ringer haben sich die Kenntnisse um die Regulation dieses wichtigen Regulators enorm erweitert. Die hier vorgestellten Calcium‐Kanalblocker sind alle Vasodilatatoren, aber dies in einem unterschiedlichen Ausmaß. Während die Nicht‐DHPs aufgrund ihrer vaskulären und kardialen Effekte antihypertensive, antiarrhythmische und antianginöse Wirkungen aufweisen, sind bei den DPHs im Gegensatz zu ihrer starken Senkung des koronaren und peripheren Widerstands die Wirkungen auf die Schrittmacherfunktionen (AV‐Überleitung) und die Dehnungsantwort am Herzen (Kontraktilität) kaum ausgeprägt. Dies zeigt, dass nicht alle Calcium‐Kanalblocker gleich sind und eine patientenorientierte erkrankungsangepasste Arzneimittelauswahl erfolgen muss.
Pharmakologie der Calcium‐Antagonisten: Wirkstoffe am Typ‐L‐Calciumkanal
Authors: Knorr Andreas
Published: August 2005

Ca2+‐Antagonisten sind eine chemisch und pharmakologisch sehr divergente Wirkstoffklasse. Die hauptsächlich therapierelevanten 1, 4‐Dihydropyridine, Phenykalkylamine und Benzothiazepine binden an drei unterschiedlichen Bindungsorten an der die Kanalpore bildenden α1c‐Untereinheit des Typ‐L‐Ca2+‐Kanals. Die Interaktionen mit dem Ca2+‐Kanal sind gut charakterisiert. Die Stoffklassen unterscheiden sich in ihrer Gewebespezifität und damit in ihrer Wirkcharakteristik: 1, 4‐Dihydropyridine sind vornehmlich peripher vasodilatierend, die Vertreter der beiden anderen haben eine stärkere kardiodepressive Wirkung. Die größte Wirkstoffgruppe, die 1, 4‐Dihydropyridine, finden die breiteste Anwendung in der Behandlung des Bluthochdrucks. Verapamil wird vor allem für die Therapie der supraventrikulären Arrhythmien eingesetzt. Weitere Einsatzgebiete sind die Behandlung der stabilen Angina pectoris und subarachnoidale Blutungen (nur Nimodipin).
Stellenwert von Nimodipin in der Demenztherapie: Calcium‐Hypothese der Demenz
Authors: Eckert Anne
Published: August 2005

Die Calcium‐Hypothese der Demenz bildet die Rationale für den therapeutischen Einsatz des Calcium‐Antagonisten Nimodipin zur Behandlung von Demenzerkrankungen. Die Datenlage zur klinischen Wirksamkeit von Nimodipin zur Behandlung dementieller Syndrome wird in der Literatur allerdings kontrovers diskutiert, wenngleich eine kleine Zahl klinischer Studien eine Überlegenheit von Nimodipin gegenüber Plazebo hauptsächlich bei vaskulärer Demenz nachweisen konnte.
Therapie nach aneurysmatischer Subarachnoidalblutung: Einsatzgebiet für Calcium‐Antagonisten
Authors: Nemec Karin , Greif Robert
Published: August 2005

Die Wirkstoffklasse der Calcium‐Antagonisten ist seit ihrer Markteinführung aus der Therapie kardiovaskulärer Erkrankungen nicht mehr wegzudenken. Obwohl ihre klinische Bedeutung in den letzten Jahren im Sinken begriffen war und eine Neubewertung stattgefunden hat, gibt es für einige Indikationen keinen Ersatz für die Anwendung von CalciumAntagonisten. Dazu gehören die Prophylaxe und Therapie ischämischer neurologischer Defizite infolge zerebraler Vasospasmen nach aneurysmatischer Subarachnoidalblutung (SAB).
Pharmazeutische Betreuung der Patienten in der Apotheke: Therapie mit Calcium‐Antagonisten
Authors: Diers Karsten
Published: August 2005

Patienten, die mit einer Verordnung über Calcium‐Antagonisten in die Apotheke kommen, sind in den meisten Fällen entweder Hypertoniker oder leiden unter einer koronaren Herzkrankheit. Im Falle der Hypertonie ist die Krankheits‐ und Therapieeinsicht der Patienten gering, zudem sind sie nicht selten schlecht versorgt und therapiert. Das Auftreten von unerwünschten Arzneimittelwirkungen ist der Hauptgrund für Non‐Compliance bei Hypertonikern. Calcium‐Antagonisten nehmen hier vor allem wegen des Auftretens peripher Ödeme und Flush im Vergleich zu anderen Antihypertensiva eine Spitzenstellung ein. Die Pharmazeutische Betreuung hat als Hauptaufgabe, dieses Problem zu lösen. Neben der umfassenden Beratung des Patienten über seine Erkrankung und der zur Verfügung stehenden Therapiemöglichkeiten in Zusammenarbeit mit dem behandelnden Arzt sollte in der Apotheke mittels des Arzneidossiers eine Non‐Compliance detektiert, die Gründe hierfür identifiziert und mit Patient und Arzt gemeinsam nach Wegen zur Lösung gesucht werden. Hierzu ist die stärkere Einbindung des Patienten in die Therapie, das gemeinsame Festlegen von Therapiezielen und die eigenständige Überprüfung durch den Patienten Grundvoraussetzung.
Der Lotus – Heilige Pflanze mit Selbstreinigungseffekt
Authors: Junghans Thomas
Published: August 2005

Die früher zu den Seerosengewächsen gestellte Lotusblume (Gattung Nelumbo) wird mit ihren weltweit nur zwei Arten heute zumeist in eine eigene Familie der Nelumbonaceae eingeordnet.
Heilungschancen durch embryonale Stammzellen?
Authors: Zündorf Ilse , Dingermann Theo
Published: August 2005

Mitte Mai ging es durch die Medien und Woo Suk Hwang wurde plötzlich zum bekanntesten Südkoreaner: Er hatte 11 maßgeschneiderte embryonale Stammzelllinien für sowohl männliche als auch weibliche Patienten unterschiedlichen Alters und mit verschiedenen Erkrankungen durch Kerntransfer generiert.
Plasma protein profiling: Unique and stable features of individuals
Authors: Nelsestuen Gary L. , Zhang Yan , Martinez Michael B. , Key Nigel S. , Jilma Bernd , Verneris Michael , Sinaiko Alan , Kasthuri Raj S.
Published: August 2005

Carefully controlled ZipTip extraction of diluted human plasma or serum was combined with MALDI‐TOF‐MS to produce highly reproducible protein profiles. Components detected included apolipoproteins CI, CII and CIII as well as transthyretin and several isoforms of each protein that are created by glycosylation or other modification and by proteolytic processing. Profiles of healthy individuals all contained the same 15 components. Others were found in plasma from individuals with disease. Profiles were analyzed by peak ratios within the same spectrum. Reproducibility for multiple assays was generally 4 to 10%. Within the healthy population, a given peak ratio occurred with a range of about fourfold. However, peak ratios of multiple samples from the same individual showed a much lower range, typically ±10%. In fact, each individual displayed a personal protein profile that changed very little over time. Because of the stability of protein profiles over time within individuals, these results suggest further studies may discover that certain profile characteristics or changes in an individual's profile may be a sign of current or future disease, even when the altered profile remains within the range for healthy individuals.
Effects of vapor‐phase‐formaldehyde treatments on thermal conductivity and diffusivity of ramie fibers in the range of low temperature
Authors: Yamanaka Atsuhiko , Yoshikawa Masatoshi , Abe Shunzo , Tsutsumi Masayuki , Oohazama Takeshi , Kitagawa Tooru , Fujishiro Hiroyuki , Ema Kimiko , Izumi Yoshinobu , Nishijima Shigehiro
Published: August 2005

To understand the influence to thermal conductivity by bridging in the polymer fibers, the thermal conductivity, and thermal diffusivity of ramie fiber and those bridged by formaldehyde (HCHO) using vapor‐phase method (VP‐HCHO treatment) were investigated in the lower temperature range. The thermal conductivities of ramie fiber with and without VP‐HCHO treatments decreased with decreasing temperature. Thermal diffusivities of ramie fiber with and without VP‐HCHO treatments were almost constant in the temperature range of 250–50 K, and increased by decreasing temperature below 50 K. Thermal conductivity and thermal diffusivity of ramie fiber decreased by VP‐HCHO treatment. The crystallinities and orientation angles of ramie fibers with and without VP‐HCHO treatment were measured using solid state NMR and X‐ray diffraction. These were almost independent of VP‐HCHO treatment. Although tensile modulus decreased slightly by VP‐HCHO treatment, the decrease could not explain the decrease in thermal conductivity and diffusivity with decreasing sound velocity. The decrease of the thermal diffusivity and thermal conductivity by VP‐HCHO treatment suggested the possibility of the reduction of the mean free path of phonon by HCHO in VP‐HCHO treated ramie fiber. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2754–2766, 2005
Management tools for the evaluation of compliance and costs in the production of chemical–pharmaceutical companies
Authors: Rank Franziska , Steven Wolfgang , Scheuermann Hans‐Jörg , Wozniewski Thomas , Müller Rainer Helmut
Published: August 2005

Due to the stringent and increasingly demanding Good Manufacturing Practice (GMP) and customer requirements, companies within the chemical–pharmaceutical sector share the enormous challenge of evaluating and measuring compliance and costs. The need for implementing a compliance measuring tool for production was identified within the Schering AG and activities were undertaken. The established compliance evaluation system and the first model for a compliance cost system proved to be well‐structured and suitable for the production. Consequently, the systems can be adapted by other areas and chemical–pharmaceutical companies and may even be expanded to other areas, such as Good Laboratory Practice (GLP) and Good Clinical Practice (GCP). Copyright © 2005 John Wiley & Sons, Ltd.
Establishment of a GLP compliance program for drug safety studies at SIMM
Authors: Li Xiang‐Hong , Ren Jin
Published: August 2005

The document ‘Good Laboratory Practice Regulations for Nonclinical Drug Safety Studies’ issued in China on 14 October 1999 was updated by China's State Food and Drug Administration (SFDA) and became effective as of 1 September 2003. In October 2003, SFDA started to commission Good Laboratory Practice (GLP) inspections. Since then, China has adopted a national GLP conformity accreditation system, and it became increasingly required that drug safety studies in China were to be carried out in accordance with the principles of GLP regulations. Development of a standardized safety study platform also plays an important role in the strategy ‘Establishing National Drug Innovation System in Knowledge Innovation’, led by Shanghai Institute of Materia Medica (SIMM), China Academy of Sciences. Demands from outside and inside SIMM required that a GLP compliance program for drug safety studies be established at SIMM. However, the establishment of a GLP compliance program was challenging. In this article, the strategies adopted and the progress made towards meeting the challenges of establishing a GLP compliance program for drug safety studies at SIMM are described. Copyright © 2005 John Wiley & Sons, Ltd.
Algorithms for crystallographic groups
Authors: Eick Bettina , Souvignier Bernd
Published: August 2005

This article presents a survey of the algorithms for space groups and crystallographic groups available in the computer algebra system Gap and in the software packages Carat and Cryst. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
HF–HL method: Combination of Hartree–Fock and Heitler–London approximations
Authors: Corongiu Giorgina
Published: August 2005

Comparison of Hartree–Fock (HF) and Heitler–London (HL) ground‐state computations for H2, LiH, Li2, BH, HF, and F2 leads to an approach that is a variational combination of the two approximations. This new HF–HL ab initio method is implemented at three levels. The first level variationally optimizes the linear combination of traditional HF and HL functions. It correctly predicts both molecular formation and dissociation for the above molecules, features not consistently found in either the HF or the HL approximations. The second level introduces valence correlation and the third level inner shells correlation, adapting standard multi‐configuration techniques to the HF–HL function. The procedure for both levels has been preliminarily applied to LiH and Li2 and found to yield very encouraging results when compared to experimental data. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
The rothein peptides from the skin secretion of Roth's tree frog Litoria rothii. Sequence determination using positive and negative ion electrospray mass spectrometry
Authors: Brinkworth Craig S. , Bowie John H. , Bilusich Daniel , Tyler Michael J.
Published: August 2005

The secretion from the dorsal glands of the frog Litoria rothii contains a series of new peptides including rothein 1 (SVSNIPESIGF‐OH, a neuropeptide which contracts smooth muscle), a number of inactive rothein 2 and 3 peptides (e.g. rothein 2.1, AGGLDDLLEPVLNSADNLVHGL‐OH), and a new proline rich peptide, named rothein 4.1 (AEILFGDVRPPWMPPPIFPEMP‐OH), which shows neither antimicrobial nor neuronal nitric oxide synthase (nNOS) activity. Two known neuropeptides of the caerulein family [e.g. caerulein, pEQDY(SO3)TGWMDF‐NH2] together with a series of known caerin 1 antibiotic and nNOS‐inhibiting peptides (e.g. caerin 1.1, GLLSVLGSVAKHVLPHVVPVIAEHL‐NH2) were also identified. Positive ion electrospray mass spectrometry (ES‐MS) was used as the primary method to investigate the sequences of the new peptides. Negative ion ES‐MS was used to fill in any gaps in the positive ion data and, finally, Edman automated sequencing was used to differentiate between Leu and Ile and to confirm the sequences determined by mass spectrometry. Copyright © 2005 John Wiley & Sons, Ltd.
A study of common discovery dosing formulation components and their potential for causing time‐dependent matrix effects in high‐performance liquid chromatography tandem mass spectrometry assays
Authors: Xu Xiaoying , Mei Hong , Wang Shiyong , Zhou Qiao , Wang Ganfeng , Broske Lisa , Pena Adrienne , Korfmacher Walter A.
Published: August 2005

Hydroxyproyl‐β‐cyclodextran (HPBCD), methyl cellulose (MC), Tween 80 and PEG400 are commonly used in dosing formulations in pharmacokinetic (PK) studies during the early drug discovery stage. A series of studies was designed to evaluate the potential matrix effects of these dosing vehicles when the samples are assayed by high‐performance liquid chromatography combined with tandem mass spectrometry (HPLC/MS/MS). These dosing vehicles were dosed into the rats via either an intravenous (IV) or an oral route (PO) and plasma samples were collected for a 24‐h post‐dose period. Five test compounds with CLog P values ranging from 0.9 to 5.4 were spiked into the collected rat plasma. After protein precipitation, these samples were analyzed using a generic fast‐gradient HPLC/MS/MS method. Three popular mass spectrometers (Thermo‐Finnigan Quantum with ESI and APCI, AB‐Sciex API 3000 with ESI and APCI, and Waters‐Micromass Quattro Ultima with ESI) were used to test these plasma samples. Results indicated that there was no observed matrix effect for all five compounds when 20% HPBCD or 0.4% MC was used as the vehicle in either the IV or the PO route, respectively. In addition, 0.1% Tween 80 dosed either IV or PO caused significant ion suppression (50–80%, compared to results obtained from plasma samples free from vehicles) for compounds that eluted at the beginning of the chromatogram. Also, PEG400 when used in an oral formulation caused significant ion suppression (30–50%) for early eluting compounds. These matrix effects were not only ionization mode (ESI or APCI) dependent, but also source design (Thermo‐Finnigan, AB‐Sciex or Waters‐Micromass) dependent. Overall, the APCI mode proved to be less vulnerable to matrix effects than the ESI mode. Some possible mechanisms of these matrix effects are proposed and simple strategies to avoid these matrix effects are discussed. Copyright © 2005 John Wiley & Sons, Ltd.