bluuebunny/crossref_metadata_2025 huggingface dataset:
Template-assisted Formation of Charge-transfer Complex by a Mixed Supramolecular Ladder Complex
Authors: Sugimoto Takahiro , Suzuki Takayuki , Shinkai Seiji , Sada Kazuki
Published: January 2007

A 2,6-naphthalenediol-modified BisPYBOX (2,6-bis(benzoxazol-2-yl)pyridine (benzoPYBOX)) ligand and a naphthaldiimide-modified BisPYBOX ligand were newly designed and synthesized as a bar for ladder structure formation. The mixing of these two BisPYBOX ligands formed supramolecular ladders along a polymeric secondary dialkylammonium cations as templates to yield charge-transfer (CT) complexes in solution.
Effects of Coverage of Silica-supported Ni Catalysts with Silica upon Formation of Carbon Nanofibers with Uniform Diameter by Ethylene Decomposition
Authors: Nakagawa Keizo , Takenaka Sakae , Imagawa Satoshi , Matsune Hideki , Kishida Masahiro
Published: January 2007

Carbon nanofibers with uniform diameter of 10–15 nm were produced by the decomposition of ethylene over silica-supported Ni catalysts covered with silica layers.
Generation of Functional Dopamine Neurons from Neural Precursor Cells Isolated from the Subventricular Zone and White Matter of the Adult Rat Brain Using Nurr1 Overexpression
Authors: Shim Jae-Won , Park Chang-Hwan , Bae Yong-Chul , Bae Jin-Young , Chung Seungsoo , Chang Mi-Yoon , Koh Hyun-Chul , Lee Hyun-Seob , Hwang Se-Jin , Lee Ki-Hwan , Lee Yong-Sung , Choi Cha-Yong , Lee Sang-Hun
Published: January 2007

Neural precursor (NP) cells from adult mammalian brains can be isolated, expanded in vitro, and potentially used as cell replacement source material for treatment of intractable brain disorders. Reduced ethical concerns, lack of teratoma formation, and possible ex vivo autologous transplantation are critical advantages to using adult NP donor cells over cells from fetal brain tissue or embryonic stem cells. However, the usage of adult NP cells is limited by the ability to induce specific neurochemical phenotypes in these cells. Here, we demonstrate induction of a dopaminergic phenotype in NP cells isolated from the subventricular zone (SVZ) and white matter of rodent adult brains using overexpression of the nuclear receptor Nurr1 in vitro. Forced expression of Nurr1, a transcriptional factor specific to midbrain dopamine (DA) neuron development, caused in the adult cells an acquisition of the DA neurotransmitter phenotype and sufficient differentiation toward morphologically, phenotypically, and ultrastructurally mature DA neurons. Co-expression of neurogenic factor Mash1 and treatment with neurogenic cytokines brain-derived neurotrophic factor and neurotrophin-3 greatly enhanced Nurr1-induced DA neuron yield. The Nurr1-induced DA neurons demonstrated in vitro presynaptic DA neuronal functionality, releasing DA neurotransmitter in response to depolarization stimuli and specific DA reuptake. Furthermore, Nurr1-engineered adult SVZ NP cells survived, integrated, and differentiated into DA neurons in vivo that can reverse the behavioral deficit in the host striatum of parkinsonian rats. These findings open the possibility for the use of precursor cells from adult brains as a cell source for neuronal replacement treatment of Parkinson disease.

Disclosure of potential conflicts of interest is found at the end of this article.
Selection of Embryonic Stem Cell-Derived Enhanced Green Fluorescent Protein-Positive Dopamine Neurons Using the Tyrosine Hydroxylase Promoter Is Confounded by Reporter Gene Expression in Immature Cell Populations
Authors: Hedlund Eva , Pruszak Jan , Ferree Andrew , Viñuela Angel , Hong Sunghoi , Isacson Ole , Kim Kwang-Soo
Published: January 2007

Transplantation of mouse embryonic stem (mES) cells can restore function in Parkinson disease models, but can generate teratomas. Purification of dopamine neurons derived from embryonic stem cells by fluorescence-activated cell sorting (FACS) could provide a functional cell population for transplantation while eliminating the risk of teratoma formation. Here we used the tyrosine hydroxylase (TH) promoter to drive enhanced green fluorescent protein (eGFP) expression in mES cells. First, we evaluated 2.5-kilobase (kb) and 9-kb TH promoter fragments and showed that clones generated using the 9-kb fragment produced significantly more eGFP+/TH+ neurons. We selected the 9-kb TH clone with the highest eGFP/TH overlap for further differentiation, FACS, and transplantation experiments. Grafts contained large numbers of eGFP+ dopamine neurons of an appropriate phenotype. However, there were also numerous eGFP+ cells that did not express TH and did not have a neuronal morphology. In addition, we found cells in the grafts representing all three germ layers. Based on these findings, we examined the expression of stem cell markers in our eGFP+ population. We found that a majority of eGFP+ cells were stage-specific embryonic antigen-positive (SSEA-1+) and that the genetically engineered clones contained more SSEA-1+ cells after differentiation than the original D3 mES cells. By negative selection of SSEA-1, we could isolate a neuronal eGFP+ population of high purity. These results illustrate the complexity of using genetic selection to purify mES cell-derived dopamine neurons and provide a comprehensive analysis of cell selection strategies based on tyrosine hydroxylase expression.

Disclosure of potential conflicts of interest is found at the end of this article.
Influence of structure on the time-dependent behaviour of a stiff sedimentary clay
Authors: Sorensen K. K. , Baudet B. A. , Simpson B.
Published: January 2007

In this paper results from laboratory tests on London Clay and artificially cemented kaolin are presented and used to develop a preliminary framework for the time-dependent behaviour of soils, applicable to stiff clays and other soils. In the same way that the natural structure of clays has been shown to influence their monotonic behaviour, it is shown that it can also alter their response to changes in strain rate. The relative influence of the two main components of post-sedimentation structure—over-consolidation and diagenesis—on the time-dependent behaviour of London Clay was investigated in triaxial compression tests. The study was carried out in two steps, comparing first the behaviours of normally and overconsolidated reconstituted samples of London Clay subjected to stepwise changes in strain rate, and then the behaviours of overconsolidated reconstituted and undisturbed London Clay samples. The test results show that overconsolidation does not seem to affect the response of reconstituted London Clay to strain rate changes, which is consistent with published data on other stiff clays. However, intact and reconstituted overconsolidated samples show different behaviours, highlighting that it is the elements of structure resulting from diagenesis that influence the time-dependent behaviour of London Clay. Effects of cementing on strain rate sensitivity were investigated in triaxial compression of artificially cemented kaolin. The results obtained were different from the results for London Clay, suggesting that the difference in strain rate effects in the intact and reconstituted London Clay cannot be simply associated with cementing. A preliminary framework is proposed, where the time-dependent behaviour of soil depends on its particulate or continuum nature.
Characteristics of the London Clay from the Terminal 5 site at Heathrow Airport
Authors: Hight D. W. , Gasparre A. , Nishimura S. , Minh N. A. , Jardine R. J. , Coop M. R.
Published: January 2007

The innovative engineering approach adopted for the new Terminal 5 at Heathrow Airport called for an advanced investigation of the London Clay strata, including detailed in situ profiling and stress path laboratory testing on high-quality rotary-cored samples. Although the scope of the investigations exceeded that normally specified for conventional design, questions relating to the structure and anisotropy of stiffness and strength of the clay remained that could not be answered. Further research was required, and the deep excavations at the site provided the opportunity for a team from Imperial College to take multiple block samples from three depths, supplemented by two additional dedicated rotary-cored boreholes. Intensive research was performed at Imperial College on these samples, as described in three companion papers by Gasparre et al. and Nishimura et al. This overview paper integrates the findings from the recent research with those from the commercial investigation and with earlier studies to extend our understanding of the geology and key characteristics of this stiff clay, and their variation with depth. The influence of lithology, structure and destructuring is examined, and the practical implications of the work are discussed.
Shear strength anisotropy of natural London Clay
Authors: Nishimura S. , Minh N. A. , Jardine R. J.
Published: January 2007

The paper reports the shear strength anisotropy of the natural, highly overconsolidated, London Clay from Heathrow Terminal 5 as established by comprehensive hollow cylinder apparatus (HCA) testing. Multiple high-quality block samples from 5·2 m and 10·5 m below ground level provided samples for suites of undrained stress-path shear tests performed after consolidation to effective stress states similar to those estimated in situ. The direction of the major principal stress axis, α (or of the principal stress increment, αdσ), and relative magnitude of the intermediate principal stress, b = (σ2 − σ3)/(σ1 − σ3), were chosen as the controlled stress-related variables and their influence on the peak shear strength was investigated. Strong shear strength anisotropy was proven, and a potential effect of the parameter b was also detected. With b = 0·5, for example, a minimum was noted in peak q/p′ at around α = 45–67°, and the maximum value, which was larger by some 40%, developed at α = 0°. A limited set of data obtained with larger test specimens suggested a possibility that loading with α = 90° could also lead to relatively low shear strength. The pre-failure pore water pressure development reflected anisotropy of the deformation characteristics at smaller strains and contributed to the total-stress undrained shear strength anisotropy. Regarding the influence of b, the Mohr–Coulomb failure line passing through the data for b = 0 or 1 provided a lower bound of all the data for a given value of α. The investigation of anisotropy was extended to deeper horizons of the stratum through profiling tests involving triaxial extension and simple shear conditions. Although the results confirmed the general patterns of anisotropy observed at 5·2 and 10·5 m below ground level, the degree of anisotropy appeared to become stronger with depth.
Predicting the stand-up time of temporary London Clay slopes at Terminal 5, Heathrow Airport
Authors: Kovacevic N. , Hight D. W. , Potts D. M.
Published: January 2007

The paper describes the results of finite element analyses of the temporary slope geometries in London Clay at London Heathrow Airport's Terminal 5. The aims of the analyses were to examine the times before failures developed, and to identify the failure mechanisms involved. The brittle behaviour of the London Clay was modelled, and the effects of progressive failure were taken into account. The possible presence of tectonic shears with their strength close to residual was considered by comparing analyses with and without a tectonic shear zone. The predicted time to failure of the slopes and the form of the failure, whether shallow or deep-seated, were determined by a combination of the assumed permeability profile and whether or not allowances were made for increases in permeability as the clay swelled, the average surface suction, the in situ K0 profile, the depth of excavation, and whether or not a low-strength tectonic shear surface was present in the slope. The analyses fall into the category of Class A predictions, and were used in the assessment of how long temporary slopes to deep excavations could be left open before backfilling, and how the slopes should be monitored.
A biostratigraphy for the London Clay in London
Authors: De Freitas M. H. , Mannion W. G.
Published: January 2007

Biostratigraphy enables specific layers of strata to be given a unique stratigraphic address that can be used to identify the horizons in which in situ tests are conducted and from which samples for testing are collected. This is particularly valuable when working in fine-grained deposits, where stratigraphic position is not easily recognised by lithology alone, and permits any data bank of geotechnical values and performance to be used without fear of confusing one stratigraphic layer with another. Construction in the London Clay Formation, and its supporting research, has necessitated an accurate and speedy method for identifying, with a precision of centimetres, the stratigraphic layer from which geotechnical data have been obtained. The principles that enable biostratigraphy to be used for this purpose are explained and illustrated with reference to the London Clay Formation in London: this approach can be used in most sedimentary strata. An example of biostratigraphic data used in London is presented.
Stock market prediction using technical analysis
Authors: Bradic-Martinovic Aleksandra
Published: January 2007

Technical analysis (TA) is a form of analyzing market encompassing supply and demand of securities according to the study of their prices and trading volume. Using the appropriate methods, TA aims to identify price movements in the stock market, futures or currencies. In short, TA analysis is the process by which "future price movements are formulated according to the price history". TA originates from the work of Charles Dow and his conclusions about the global behavior of the market, as well as from Elliot Wave Theory. Dow did not regard its theory as a tool for stock market movement prediction, nor as a guide for investors, but as a kind of barometer of general market movements. The term TA methods encompasses all the methods used in tracking prices aiming to clearly predict future events. Many different methods, mainly statistical, are used in technical analysis, the most popular ones being: establishing and following trends using moving average, recognizing price momentum, calculating indicators and oscillators, as well as cycle analysis (structure indicators). It is also necessary to point out that TA is not a science in the true meaning of the term, and that methods it uses frequently deviate from the conventional manner of their use. The main advantage of these methods is their relative ease of use, aiming to give as clear picture as possible of price movements, while at the same time avoiding the use of complicated and complex mathematical methods. The reason for this is simple and is reflected in the dynamics of financial markets, where changes occur during short periods of time and where prompt decision-making is of vital importance.
Quality of life in patients with chronic renal failure
Authors: Petrovic Lada , Mitic Igor , Bozic Dusan , Vodopivec Slavenka , Djurdjevic-Mirkovic Tatjana
Published: January 2007

Introduction. Hemodialysis and transplantation are performed not only to replace renal function, but also to improve patients' quality of life. The aim of our investigation was to compare the quality of life in patients with chronic renal failure (CRF) before and after the introduction of active therapy. Material and methods. We tested 76 patients (pts): 20 pts on conservative therapy (CT), 21 pts on chronic hemodialysis and 35 pts with renal transplantation. A questionnaire (combining two questionnaires) was used to investigate the physical, emotional and social aspects of health. Results. In regard to physical health of transplantation patients (TP) it was established that work capacity and activities were less damaged, whereas physical activity was highest in pts on CT. Social activity was limited in a higher percentage in TP (40%) than in hemodialysis patients (HD) (19%), while family relationships were most damaged in pts on HD (28.57%). Discomforts were most common in pts on HD. The highest percentage of pts estimated their health status as good or average, but their health status improved after transplantation in 82.86% that is in 57.14% after HD. It was similar with the quality of life: 28.57% of kidney transplant patients rated their quality of life as very good, and 54.28% rated it as good; 38.09% of HD patients rated their quality of life as very good, whereas only 5% of CT patients rated it as very good, and 20% as good. .
Tension-free vaginal tape obturator system in the treatment of stress urinary incontinence
Authors: Djurdjevic Srdjan
Published: January 2007

Surgical approach to the treatment of female stress urinary incontinence has changed significantly since 1995, when Ulmsten first described the procedure providing tension-free support in the middle part of urethra. Although retropubic placement of TVT tapes seemed to meet all the standards of minimally invasive surgical procedures, the occurrence of complications (bleeding, hematomas, and bladder, urethral of intestinal injuries) necessitated a new obturator approach. This study presents a transobturator approach to TVT tapes placement (Gynecare, Johnson-Johnson Company) with "inside-out" technique, first shown by De Leval in 2003. During 2005, 6 TVT tapes for stress urinary incontinence treatment were placed at the Clinic of Gynecology and Obstetrics in Novi Sad without any intra or post-operative complications. .
Effects of interferons on hepatitis C virus infection
Authors: Bojic Ivanko , Dokic Ljubisa , Minic Svetlana
Published: January 2007

Introduction. The consequences of hepatitis C virus infections (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma) are one of the major problems in clinical medicine. The persistence of infection in spite of high specific antibody titre suggests that the virus has the ability to "escape" the immunological response. Interferon therapy. Interferons are important components of the early host response to infection. They have antiviral, antiproliferative, and immunomodulatory activities. Many viruses have developed the ability to "annul" or alleviate the action of interferon by preventing its synthesis or by interfering with signaling pathways in the cells. During acute infection some of the non-structural proteins of HCV block regulatory factors that are responsible for the synthesis of endogenous infection. Within a cell, interferon induces a number of genes to produce proteins that prevent virus replication. Among them, the most important are RNA-dependent protein kinase and the eukaryotic initiation factor. However, viral proteins, especially viral envelope proteins and nonstructural protein 5A, prevent their phosphorylation and activation which enhance virus replication. These are the facts that have to be considered when using IFN in chronic hepatitis C patients. .
A gastrointestinal stromal tumor: Case report
Authors: Vukovic Milivoje , Moljevic Nebojsa , Krivokuca Dragan
Published: January 2007

Introduction. Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They frequently occur in the stomach and small intestine, but they rarely occur in the colon and rectum. Case report. This is a case report of a patient with a GIST involving the cecum, and acute obstruction of the small intestine. A 47-year- old male patient was admitted to the emergency surgery department with abdominal pain and distension lasting for a few days. Clinical examination revealed tenderness in the right iliac fossa. Routine hematologic testing revealed anemia, and abdominal x-ray multiple air-fluid levels in the small intestine. Based on the clinical findings, we decided to perform an explorative laparotomy. A large cecal tumor was detected. The proximal parts of the small intestine were severely distended. Discussion and Conclusion. GISTs are more common in the stomach (60-70%) and the small intestine (25-35%), than in the colon, rectum and esophagus. The most frequent complications associated with GISTs are obstructions and hemorrhages. Surgical resection is the primary treatment of GISTs. Radiotherapy and chemotherapy are generally ineffective. Continuous postoperative follow-up is necessary, because most recurrences occur within the first 2 years after complete surgical resection. In the past few years, surgical resection was followed by adjuvant tyrosine kinase inhibitor therapy. .
Large-scale dynamo of accretion disks around supermassive nonrotating black holes
Authors: Poplavsky A.L. , Kuznechik O.P. , Stetyukevich N.I.
Published: January 2007

In this paper one presents an analytical model of accretion disk magnetosphere dynamics around supermassive nonrotating black holes in the centers of active galactic nuclei. Based on general relativistic equations of magneto hydrodynamics, the nonstationary solutions for time-dependent dynamo action in the accretion disks, spatial and temporal distribution of magnetic field are found. It is shown that there are two distinct stages of dynamo process: the transient and the steady-state regimes, the induction of magnetic field at t > 6:6665 x 1011GM/c3 s becomes stationary, magnetic field is located near the innermost stable circular orbit, and its value rises up to ~ 105 G. Applications of such systems with nonrotating black holes in real active galactic nuclei are discussed.
Orbits for sixteen binaries
Authors: Cvetkovic Z. , Novakovic B.
Published: January 2007

In this paper orbits for 13 binaries are recalculated and presented. The reason is that recent observations show higher residuals than the corresponding ephemerides calculated by using the orbital elements given in the Sixth Catalog of Orbits of Visual Binary Stars. The binaries studied were: WDS 00182+7257 = A 803, WDS 00335+4006 = HO 3, WDS 00583+2124 = BU 302, WDS 01011+6022 = A 926, WDS 01014+1155 = BU 867, WDS 01112+4113 = A 655, WDS 01361?2954 + HJ 3447, WDS 02333+5219 = STT 42 AB,WDS 04362+0814 = A 1840 AB,WDS 08017?0836 = A 1580, WDS 08277?0425 = A 550, WDS 17471+1742 = STF 2215 and WDS 18025+4414 = BU 1127 Aa-B. In addition, for three binaries - WDS 01532+1526 = BU 260, WDS 02563+7253 = STF 312 AB and WDS 05003+3924 = STT 92 AB - the orbital elements are calculated for the first time. In this paper the authors present not only the orbital elements, but the masses dynamical parallaxes, absolute magnitudes and ephemerides for the next five years, as well.
Progress report on the monitoring active late-type stars in 2005/2006 and the analysis of V523 Cas
Authors: Zboril M. , Djurasevic G.
Published: January 2007

We present the light curve analysis of late-type binary V523 Cas for the season 2005. The spot has been revealed on the secondary. According to theoretical considerations, the spot appeared to be hotter than the surrounding photosphere and located at middle latitudes (the radius 40? and latitude 48?). The light curves for other stars in the observational list (many of them again with O'Connell effect), for the same season, have been made electronically available. These objects are SV Cam, IV Dra, BI Vul, DD Com, 12 Cam and II Peg.
Program of telluric lines monitoring
Authors: Vince I. , Kos P. , Latkovic O. , Martinovic N. , Gosic M. , Stojadinovic J.
Published: January 2007

A new observational program of telluric lines monitoring was introduced at Belgrade Astronomical Observatory. The ultimate goal of this program is to investigate the properties of Earth?s atmosphere through modeling the observed profiles of telluric lines. The program is intend to observe infrared molecular oxygen lines that were selected according to spectral sensitivity of the available CCD camera. In this paper we give the initial and the final selection criteria for spectral lines included in the program the description of equipment and procedures used for observations and reduction, a review of preliminary observational results with the estimated precision, and a short discussion on the comparison of the theoretical predictions and the measurements.
Caries prevalence in adolescents in Eastern Bosnia: Foca municipality
Authors: Stojanovic Nikola , Krunic Jelena
Published: January 2007

Caries is the most frequent oral disease in all age groups. Aim: The aim of this study was to determine dental status and caries prevalence in adolescents in the Eastern Bosnian region, in Foca municipality Materials and methods: The study comprised 300 pupils of secondary schools, of both sexes and aged between 15 and 18 in Foca municipality. Dental check-up was conducted by a single dentist using daylight, dental mirror and dental probe. Caries prevalence was analyzed using the DMFT index. Results: Results showed that the dominant components of DMFT were filled (51.7%) and decayed teeth (36.8%) while extracted teeth were least frequent (11.8). Initial caries was observed most frequently in upper (48%) and lower (39.7%) molars and least frequently in lower anterior teeth (8.4%). Deep caries lesions were most often found in upper (35,7%) and lower (33.3%) molars and rarely in lower anterior teeth (3.3%). Conclusion: Adolescents in Eastern Bosnia (Foca municipality) have great number of carious and unrestored teeth and, therefore, the implementation of primary dental healthcare system is necessary as well as looking for a solution to this problem.
Mechanochemical activation of batch during fabrication of highly-porous cordierite materials based on natural oxide compounds
Authors: Antsiferov V.N. , Porozova S.E. , Karmanov V.I.
Published: January 2007

Using X-ray diffraction analysis and infrared spectroscopy techniques, the effect of additives on phase composition variation during mechanochemical activation of a kaolin-containing cordierite batch was investigated. It was shown that introduction of Trilon B permits fixing of the start of cordierite synthesis already during batch activation. It was established that mechanochemical activation of a cordierite batch doped with Trilon B results in an increase of the strength of cordierite samples prepared by polymer matrix duplication.
Influence of the phase composition of refractory materials on creep
Authors: Terzic A. , Pavlovic Lj. , Milutinovic-Nikolic A.
Published: January 2007

In this paper, the relationship between the creeping effect and mineralogical characteristics of the applied binding phase for various refractory materials (high-alumina materials, with high or low impurity content, tar bonded either magnesite or dolomite materials and silicate bonded chrom-magnesite materials) is presented. The mechanism of creeping is analyzed and the activation energy for creep for each investigated material is obtained and discussed. All investigated materials are creep sensitive under investigated conditions and have similar activation energies for creep except high-alumina refractories with a low impurity content.
The effect of pressing pressure on the magnetic properties of amorphous Co80Ni20 alloy powder
Authors: Simeunovic R. , Maricic A. , Kalezic-Glisovic A. , Spasojevic M.
Published: January 2007

The impact of amorphous Co80Ni20 alloy powder pressing pressure on magnetic properties was investigated. The powder was pressed at room temperature under pressures of 560 MPa, 1100 MPa and 1300 MPa. Investigation of magnetic properties was conducted by magnetic susceptibility measurement in temperature range from 290 K to 900 K. It has been determined that with a pressing pressure increase the magnetic susceptibility rises. The differential scanning calorimetry method showed that the crystallization process occurred in two stages and each crystallization stage was followed by a magnetic susceptibility change.
A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for the estimation of amlodipine in human plasma
Authors: Bhatt Jignesh , Singh Sadhana , Subbaiah Gunta , Shah Bhavin , Kambli Sandeep , Ameta Suresh
Published: January 2007

A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method has been developed and validated for the estimation of amlodipine in human plasma. Amlodipine was extracted from human plasma by using a solid‐phase extraction technique. Imipramine was used as the internal standard. A Hypersil BDS C18 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves a rapid solid‐phase extraction from plasma, simple isocratic chromatography conditions and mass spectrometric detection that enables detection at sub‐nanogram levels. The proposed method has been validated for a linear range of 0.1–10.0 ng/mL with correlation coefficient ≥0.9990. The intrarun and interrun precision and accuracy were within 10.0%. The overall recovery for amlodipine was 63.67%. Total run time was 3.2 min only. Copyright © 2007 John Wiley & Sons, Ltd.
A high‐performance liquid chromatographic method for determination of mitragynine in serum and its application to a pharmacokinetic study in rats
Authors: Janchawee Benjamas , Keawpradub Niwat , Chittrakarn Somsmorn , Prasettho Supaporn , Wararatananurak Puchong , Sawangjareon Kitja
Published: January 2007

A simple HPLC technique for determining mitragynine levels in serum was developed. The separation system consisted of a C18 column heated to 35°C, a methanol–water (80:20, v/v) mobile phase, a flow rate of 0.8 mL/min and detection in the ultraviolet at 225 nm. Mitragynine, with a retention time of 10.09 min, was well resolved from any interferences in human serum and the internal standard peak. The calibration curve was linear from 0.1 to 10 µg/mL (r = 0.9995). Extraction of mitragy‐nine from alkalinized serum using diethyl ether gave a high recovery (≥85%). The intra‐ and inter‐day precisions of the method were 4.29–5.88%RSD and 7.06–8.45%RSD, respectively. The accuracy ranged from −9.54 to +0.67%DEV. The limit of detection was 0.03 µg/mL and the lower limit of quantification was 0.1 µg/mL. Mitragynine in the stock solution was stable during 30 days of storage at 4°C. This method was successfully applied to determine the pharmacokinetic characteristics of mitragynine levels in the serum of rats after it was administered orally. Copyright © 2007 John Wiley & Sons, Ltd.
Development and validation of high‐performance liquid chromatography–tandem mass spectrometry assay for 6‐(3‐benzoyl‐ureido)‐hexanoic acid hydroxyamide, a novel HDAC inhibitor, in mouse plasma for pharmacokinetic studies
Authors: Yeo Pauline , Xin Liu , Goh Evelyn , New Lee Sun , Zeng Peizi , Wu Xiaofeng , Venkatesh P. , Kantharaj Ethirajulu
Published: January 2007

A liquid chromatography/tandem mass spectrometric method for the quantification of 6‐(3‐benzoyl‐ureido)‐hexanoic acid hydroxyamide (EX‐2), a novel histone deacetylase (HDAC) inhibitor, in mouse plasma was developed to support in‐house pharmacokinetic (PK) studies in the lead optimization stage. In order to determine the PK parameters for EX‐2 in comparison to other HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA), PXD‐101 and LBH‐589, which are currently in different stages of clinical trials, research‐grade bio‐analytical method validations were carried out for EX‐2 and these reference HDAC inhibitors, which were synthesized by in‐house medicinal chemists. The components of validation consisted of specificity, extraction efficiency, signal–response of calibration standards, lower limit of quantification, autosampler stability and accuracy and precision of quality control samples. The validated LC/MS/MS methods were accurate and precise. The calibration curve ranged from 1 to 1600 ng/mL for all the analytes. The methods developed were used to quantify EX‐2 and other HDAC inhibitors in mouse plasma obtained from pharmacokinetic studies. The results suggest that EX‐2 has better PK parameters compared with the reference drugs and is a promising drug development candidate. Copyright © 2007 John Wiley & Sons, Ltd.
In vivoevaluation of CYP1A2, CYP2A6, NAT‐2 and xanthine oxidase activities in a Greek population sample by the RP‐HPLC monitoring of caffeine metabolic ratios
Authors: Begas E. , Kouvaras E. , Tsakalof A. , Papakosta S. , Asprodini E. K.
Published: January 2007

A RP‐HPLC method was developed for the assessment of caffeine and its metabolites in urine and was used for the evaluation of the CYP1A2, CYP2A6, xanthine oxidase (XO) andN‐acetyl‐transferase‐2 (NAT‐2)in vivoactivities in 44 Greek volunteers (21 men, 23 women). Spot urine samples were analyzed 6 h after 200 mg caffeine consumption, following a 30 h methylxantine‐free diet. The major urinary caffeine metabolites are 1‐methyluric acid (1U), 5‐acetylamino‐6‐formylamino‐3‐methyluracil (AFMU), 1‐methylxanthine (1X), 1,7‐dimethyluric acid (17U) and 1,7‐dimethylxanthine (17X). CYP1A2, CYP2A6, XO and NAT‐2 activities were estimated from the metabolic ratios (AFMU + 1U + 1X)/17U, 17U/17X, 1U/(1X + 1U) and AFMU/(AFMU + 1U + 1X), respectively. Metabolites and internal standard were extracted with chloroform/isopropanol (85:15, v/v) and separated on a C18column by an isocratic HPLC system using a two‐step elution with manual switch from solvent A (0.1% acetic acid–methanol–acetonitrile, 92:4:5 v/v) to solvent B (0.1% acetic acid–methanol, 60:40, v/v), and detected at 280 nm. The method exhibited adequate metabolite separation (resolution factors >1.48), accuracy (94.1–106.3%) and intraday and interday precision <8.02 and <8.78%, respectively (n= 6). Smoking affected only CYP1A2, whereas gender had no effect in any enzyme activity. NAT‐2 exhibited bimodal distribution, 63.6% of volunteers being slow acetylators. The developed RP‐HPLC method was fully validated and successfully applied for the evaluation of CYP1A2, CYP2A6, XO and NAT‐2 activities. Copyright © 2007 John Wiley & Sons, Ltd.
Quantification of fexofenadine in human plasma by liquid chromatography coupled to electrospray tandem mass spectrometry using mosapride as internal standard
Authors: Nirogi Ramakrishna V. S. , Kandikere Vishwottam N. , Shukla Manoj , Mudigonda Koteshwara , Maurya Santosh , Komarneni Prashanth
Published: January 2007

A rapid high‐performance liquid chromatography/positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of fexofenadine in human plasma using mosapride as internal standard. Following solid‐phase extraction, the analytes were separated using an isocratic mobile phase on a reverse‐phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M+H]+ions,m/z502/466 for fexofenadine andm/z422/198 for the IS. The method exhibited a linear dynamic range of 1–500 ng/mL for fexofenadine in human plasma. The lower limit of quantification was 1 ng/mL with a relative standard deviation of less than 5% for fexofenadine. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 2 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of N‐methyl‐4‐isoleucine‐cyclosporin (NIM811) in human whole blood by high performance liquid chromatography‐tandem mass spectrometry
Authors: Li Wenkui , Luo Suyi , Hayes Michael , He Handan , Tse Francis L. S.
Published: January 2007

A liquid chromatographic method with tandem mass spectrometric detection (LC‐MS/MS) for the determination of N‐methyl‐4‐isoleucine‐cyclosporin (NIM811) was developed and validated over the concentration range 1–2500 ng/mL in human whole blood using a 0.05 mL sample volume. NIM811 and the internal standard, d12‐cyclosporin A (d12‐CsA), were extracted from blood using MTBE via liquid–liquid extraction. After evaporation of the organic solvent and reconstitution, a 10 µL aliquot of the resulting extract was injected onto the LC‐MS/MS system. Chromatographic separation of NIM811 and internal standard was performed using a Waters Symmetry RP‐8 (50 × 4.6 mm, 3 µm particle size) column. The mobile phase consists of 10 mm ammonium acetate in water (A) and acetonitrile (B), with 45% B from 0 to 0.2 min, 45 to 85% B from 0.2 to 0.8 min and 85% B from 0.8 to 2.2 min. The total run time was 3.5 min with a flow rate of 0.8 mL/min. The method was validated for sensitivity, linearity, reproducibility, stability, dilution integrity and recovery. The precision and accuracy of quality control samples at low (2.00 ng/mL), medium (20.0 and 400 ng/mL) and high (2000 ng/mL) concentrations were in the range 1.1–4.3% relative standard deviation (RSD) and −2.5–10.0% (bias), respectively, from three validation runs. The method has been used to measure the exposure of NIM811 in human subjects. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of gambogic acid in dog plasma by high‐performance liquid chromatography for a pharmacokinetic study
Authors: Hao Kun , Zhao Xiao‐Ping , Liu Xiao‐Quan , Wang Guang‐Ji
Published: January 2007

A rapid, simple and sensitive high‐performance liquid chromatography method for the quantification of gambogic acid in dog plasma was developed and validated. After acidification with hydrochloric acid, dog plasma was extracted with ethyl acetate and determined by HPLC. The analysis was carried out on a reversed‐phase C18 analytical column. The mobile phase consisted of a mixture of methanol–0.05% phosphoric acid (94:6, v/v), and the column temperature was maintained at 35°C. A constant mobile phase flow rate of 1.0 mL/min was employed throughout the analyses. The ultraviolet detector was set at 360 nm. Chromatographic separation was achieved in less than 10 min and the calibration curve was linear over a concentration range of 0.156–20 µg/mL. The intra‐assay and inter‐assay variability values were less than 10.0%. The accuracy ranged from 93.0 to 104.2%. The established method has been successfully applied to a pharmacokinetic study of gambogic acid in dogs. Copyright © 2007 John Wiley & Sons, Ltd.
A liquid chromatography–mass spectrometry assay method for simultaneous determination of amiodarone and desethylamiodarone in rat specimens
Authors: Shayeganpour Anooshirvan , Somayaji Vishwa , Brocks Dion R.
Published: January 2007

A liquid chromatographic‐mass spectrometry (LC/MS) assay method was developed for the determination of amiodarone and desethylamiodarone in rat specimens. Analytes were extracted using liquid–liquid extraction in hexane. The LC/MS system consisted of a Waters Micromass ZQ™ 4000 spectrometer with an autosampler and pump. A C18 3.5 µm (2.1 × 50 mm) column heated to 45°C was used for separation. The mobile phase consisted of methanol and 0.2% aqueous formic acid pumped at 0.2 mL/min as a linear gradient. Components eluted within 12 min. The concentrations of ethopropazine (internal standard), desethylamiodarone and amiodarone were monitored for m/z of 313.10, combination of 546.9 and 617.73, and 645.83, respectively. In plasma (0.1 mL), linearity was achieved between the peak area ratios and concentrations over the range of 2.5–1000 ng/mL for both amiodarone and desethylamiodarone (r2 > 0.999). The intraday and interday CV were equal or less than 18%, and mean error was <12%. Similarly, in homogenates containing 0.1 g of rat tissue, linearity was observed in standards ranging from 5 to 5000 ng/g. The method was successfully used to measure tissue and plasma concentrations of drug. The validated lower limit of quantitation was 2.5 ng/mL for drug and metabolite, based on 0.1 mL of plasma. Copyright © 2007 John Wiley & Sons, Ltd.
The lipophilicity estimation of 5‐arylidene derivatives of (2‐thio)hydantoin with antimycobacterial activity
Authors: Łażewska Dorota , Maludziński Piotr , Szymańska Ewa , Kieć‐Kononowicz Katarzyna
Published: January 2007

The lipophilicity of antituberculotic 5‐arylidene derivatives of (thio)hydantoin, thioacetazone and isoniazid has been determined by reversed‐phase thin‐layer chromatography (RP‐TLC). Mixtures of acetone and water (with acetone content 60–85%) were used as the mobile phase. The RM (relative lipophilicity) of each compound (except isoniazid) decreased linearly with the increasing concentration of acetone. The partition coefficients (log P) of the compounds were calculated by the use of eight computer programs (ClogP, KowWin, XlogP, AlogPs, CAChe, Pallas, Interactive analysis and Slipper) and compared with the experimental lipophilicity (RM0). According to the observations the best tools for in silico predicting log P of (2‐thio)hydantoins are programs KowWin and AlogPs. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of secnidazole in human plasma by high‐performance liquid chromatography with UV detection and its application to the bioequivalence studies
Authors: Li Xiaoyu , Sun Jianguo , Wang Guangji , Zheng Yuanting , Yan Bei , Xie Haitang , Gu Yi , Ren Hongchan
Published: January 2007

A simple, accurate, precise and sensitive HPLC‐UV method was developed for the determination of secnidazole in human plasma. Secnidazole and tinidazole (IS) were extracted from 0.2 mL of human plasma by ethyl acetate. Secnidazole was then separated by HPLC on a Diamond C18 column and quantified by ultraviolet detection at 319 nm. The mobile phase consisted of acetonitrile–aqueous 5 mm sodium acetate (30:70, v/v) containing of 0.1% acetic acid adjusted to pH 4.0, and the flow rate was 1.0 mL/min. The low limit of quantification was 0.1 µg/mL. The method was linear over the concentration range 0.1–25.0 µg/mL (R2 = 1.000). The recovery of secnidazole from human plasma ranged from 76.5 to 89.1%. Inter‐ and intra‐assay precision ranged from 3.3 to 10.7%. Secnidazole in plasma was stable when stored at ambient temperature for 8 h, at −20°C for 2 weeks and at −20°C for three freeze–thaw cycles. The developed method was successfully applied to the pharmacokinetic and bioequivalence studies between test and reference secnidazole tablets following a single 500 mg oral dosage to 20 healthy volunteers of both genders. Pharmacokinetics parameters Tmax, Cmax, AUC0−t, AUC0−∞, T1/2 were determined of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. It was concluded that the two secnidazole preparations are bioequivalence and may be used interchangeably. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of paclitaxel in human and rat blood samples after administration of low dose paclitaxel by HPLC‐UV detection
Authors: Yonemoto Haruo , Ogino Seiko , Nakashima Mihoko N. , Wada Mitsuhiro , Nakashima Kenichiro
Published: January 2007

A simple and sensitive HPLC‐UV method was developed for the determination of paclitaxel (TXL) in human and rat blood samples. 4‐Hydroxybenzoic acid n‐hexyl ester was used as an internal standard. TXL was extracted by a liquid–liquid extraction with tert‐butylmethyl ether. The disturbing peaks in the case of serum sample were removed by pre‐extraction with hexane. The separation of TXL was achieved within 25 min using an ODS column with 50% acetonitrile aqueous solution as a mobile phase at a flow rate of 1.0 mL/min. The eluent was monitored at 230 nm, and the resulted retention times of TXL and IS were 11.2 and 20.4 min. The detection limits of TXL for human plasma, serum and rat plasma samples at a signal‐to‐noise ratio of 3 were 10, 9.5 and 7.5 ng/mL, respectively. The proposed methods were applicable to the determination of TXL in human patients' plasma ranging from 15 to 27 ng/mL. Furthermore, monitoring of the time course of TXL after its single administration to rat could be demonstrated. Copyright © 2007 John Wiley & Sons, Ltd.
Pharmacokinetic study of puerarin in rat serum by liquid chromatography tandem mass spectrometry
Authors: Prasain Jeevan K. , Peng Ning , Acosta Edward , Moore Ray , Arabshahi Alireza , Meezan Elias , Barnes Stephen , Wyss J. Michael
Published: January 2007

A highly sensitive and specific atmospheric pressure chemical ionization liquid chromatography–tandem mass spectrometry method was developed for serum pharmacokinetic studies of puerarin in rats. Chromatography was carried out on a reversed‐phase Phenomenex Synergi 4 µm Fusion‐RP80 column (150 × 2.0 mm i.d.) using a mobile phase consisting of acetonitrile–water (10:90, v/v) in 10 mm NH4OAc with a flow rate of 0.2 mL/min. Puerarin was analyzed in the multiple reaction monitoring mode with a precursor/product ion transition of m/z 415/267. The method was demonstrated to be specific and sensitive, and a linear response was observed over a range of 2–5000 ng/mL in rat serum. The validated method was successfully applied to the characterization of the pharmacokinetics of puerarin in rat serum after oral administration to spontaneously hypertensive rats. The blood concentration–time profile of puerarin showed a rapid initial increase, reaching a maximum and then declining within 1 h. Puerarin could not be detected after 24 h. The main pharmacokinetic parameters for puerarin after oral administration were as follows: Cmax (3.54 ± 2.03 mg/L), Tmax (0.68 ± 0.37 h), AUC0−t (7.29 ± 3.79 mg h/L), AUC0−∞ (9.17 ± 4.87 mg h/L), T1/2 (1.7 ± 0.6 h), CL/F (7.24 ± 4.27 L/h/kg) and V/F (17.88 ± 13.55 L/h/kg). Copyright © 2007 John Wiley & Sons, Ltd.
Handling of Rayleigh and Raman scatter for PARAFAC modeling of fluorescence data using interpolation
Authors: Bahram Morteza , Bro Rasmus , Stedmon Colin , Afkhami Abbas
Published: January 2007

Fluorescence excitation‐emission matrix (EEM) measurements are useful in fields such as food science, analytical chemistry, biochemistry and environmental science. EEMs contain information which can be modeled using the parallel factor analysis (PARAFAC) model but the data analysis is often complicated due to both Rayleigh and Raman scattering. There are several established ways to deal with scattering effects. However, all of these methods have associated problems. This paper develops a new method for handling scattering using interpolation in the areas affected by first‐ and second‐order Rayleigh and Raman scatter in such a way that the interfering signal is, at best, removed. The suggested method is fast and requires no additional input other than specifying the scattering region. The results of the proposed method were compared with those obtained from common alternative approaches used for preprocessing fluorescence data before analysis with PARAFAC and were shown to be equally good for various types of EEM data. The main advantage of the interpolation method is in its lack of additional metaparameters, its algorithmic speed and subsequent speed‐up of PARAFAC modeling. It also allows for using EEM data in software not able to handle missing data. Copyright © 2007 John Wiley & Sons, Ltd.