bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Longitudinal Roughness on Friction in EHL Contacts
Authors: Jacod B. , Venner C. H. , Lugt P. M.
Published: June 2004

The effect of longitudinal roughness on the friction in EHL contacts is investigated by means of numerical simulations. In the theoretical model the Eyring equation is used to describe the rheological behavior of the lubricant. First the relative friction variation caused by a single harmonic roughness component is computed as a function of the amplitude and wavelength for a wide range of operating conditions. From the results a curve fit formula is derived for the relative friction variation as a function of the out-of-contact geometry of the waviness and a newly derived parameter characterizing the response of the lubricant to pressure variations. Subsequently, the case of a superposition of two harmonic components is considered. It is shown that for the effect on friction such a combined pattern can be represented by a single equivalent wave. The amplitude and the wavelength of the equivalent wave can be determined from a nonlinear relation in terms of the amplitudes and wavelengths of the individual harmonic components. Finally the approach is applied to the prediction of the effect of a real roughness profile (many components) on the friction. From a comparison of the results with full numerical simulations it appears that the simplified approach is quite accurate.
A Model for Temperature Rise of Polishing Process Considering Effects of Polishing Pad and Abrasive
Authors: Horng Jeng-Haur , Jeng Yeau-Ren , Chen Chun-Liang
Published: June 2004

The contact temperature plays an important role in the polishing process, which essentially is a surface contact abrasion process. This paper reports a contact temperature model to predict the temperature rise of both the abrasive-workpiece and pad-workpiece interfaces in a polishing process. In this analysis, the forces acting on an abrasive particle and an asperity of the pad are derived from a mechanistic analysis of abrasive-workpiece and pad-workpiece contact. Our results elucidate that polishing with a rigid, smooth plate is a special case of our purposed model. Theoretical predictions indicate that the temperature rise of abrasive-workpiece contact increases with an increase in particle size and density of particles, hardness of workpiece, hardness of pad, and with a decrease in thermal conductivity of workpiece. The temperature of pad-workpiece contact increases with an increase in hardness of pad and surface roughness of pad, and with a decrease in thermal conductivity of workpiece. The contact temperature rise of the pad-workpiece interface is independent of the hardness of workpiece. For a metal polishing process, the maximum contact temperature occurs at the pad-workpiece contact point for small abrasive particles and rough polishing pad with high hardness.
Sealability of Stationary Metal-to-Metal Seals
Authors: Murtagian G. R. , Fanelli V. , Villasante J. A. , Johnson D. H. , Ernst H. A.
Published: June 2004

The effectiveness of stationary metal-to-metal seals is investigated with respect to contact pressure and length, load history, and the use of sealing compounds. Laboratory cup and cone tests were carried out, and experimental results were used to develop a sealability criterion. A sealability parameter is proposed and a critical value for it was obtained from experiments. The criterion was validated through full-scale tests of tubular connections and FEA. This criterion can be used for the comparison, qualification and future performance improvements of different metal-to-metal seals, in particular those used in the petroleum industry.
Static Friction Model for Rough Surfaces With Asymmetric Distribution of Asperity Heights
Authors: Yu, Ning , Pergande, and Shaun R. , Polycarpou Andreas A.
Published: June 2004

The CEB static friction model is extended to include asymmetric distributions of asperity heights, using the normalized one-parameter Weibull distribution. The normal contact, tangential (friction), and adhesion forces are calculated for different skewness values, and are used to obtain the static friction coefficient. It is predicted that surfaces with negative skewness experience higher static friction coefficient compared to the Gaussian case, under the same external normal load, which agrees with published data. This effect is magnified for lower external loads, as is commonly encountered in microtribological applications.
Electron Transport in Deformed Carbon Nanotubes
Authors: Johnson H. T. , Liu B. , Huang Y. Y.
Published: June 2004

Carbon nanotubes are a material system of increasing technological importance with superb mechanical and electrical properties. It is well known that depending on details of atomic structure, nanotubes may be electrically conducting, semiconducting, or insulating, so deformation is believed to have strong effects on nanotube electrical properties. In this paper, a combination of continuum, empirical atomistic, and quantum atomistic modeling methods are used to demonstrate the effect of homogeneous deformation—tension, compression, and torsion—on the electrical conductance and current versus voltage (I(V)) characteristics of a variety of single wall carbon nanotubes. The modeling methods are used in a coupled and efficient multiscale formulation that allows for computationally inexpensive analysis of a wide range of deformed nanotube configurations. Several important observations on the connection between mechanical and electrical behavior are made based on the transport calculations. First, based on the I(V) characteristics, electron transport in the nanotubes is evidently fairly insensitive to homogeneous deformation, though in some cases there is a moderate strain effect at either relatively low or high applied voltages. In particular, the conductance, or dI/dV behavior, shows interesting features for nanotubes deformed in torsion over small ranges of applied bias. Second, based on a survey of a range of nanotube geometries, the primary determining feature of the I(V) characteristics is simply the number of conduction electrons available per unit length of nanotube. In other words, when the current is normalized by the number of free electrons on the tube cross section per unit length, which itself is affected by extensional (but not torsional) strain, the I(V) curves of all single walled carbon nanotubes are nearly co-linear.
Thermal Expansion of Single Wall Carbon Nanotubes
Authors: Jiang H. , Liu B. , Huang Y. , Hwang K. C.
Published: June 2004

We have developed an analytical method to determine the coefficient of thermal expansion (CTE) for single wall carbon nanotubes (CNTs). We have found that all CTEs are negative at low and room temperature and become positive at high temperature. As the CNT diameter decreases, the range of negative CTE shrinks. The CTE in radial direction of the CNT is less than that in the axial direction for armchair CNTs, but the opposite holds for zigzag CNTs. The radial CTE is independent of the CNT helicity, while the axial CTE shows a strong helicity dependence.
A Comparative Study on Various Ductile Crack Formation Criteria
Authors: Bao Yingbin , Wierzbicki Tomasz
Published: June 2004

Various fracture criteria, based on different assumptions and different mechanical models, have been proposed in the past to predict ductile fracture. The objective of this study is to assess their effectiveness and accuracy in a wide range of process parameters. A series of tests on 2024-T351 aluminum alloy, including upsetting tests and tensile tests is carried out. It is found that none of the existing fracture criteria give consistent results. Two totally different fracture mechanisms are clearly observed from microfractographs of upsetting and tensile specimens. This observation confirms that it is impossible to capture all features of ductile crack formation in different stress states with a single criterion. It is shown that different functions are necessary to predict crack formation for different ranges of stress triaxiality. Weighting functions in a wide range of stress states can be obtained by determining the fracture locus in the space of equivalent strain to fracture and stress triaxiality.
Partial Slip Rolling Wheel-Rail Contact With a Slant Rail Crack
Authors: Chen Yung-Chuan , Kuang Jao-Hwa
Published: June 2004

This paper investigates the tip characteristics of an oblique crack in the wheel-rail contact problem. The wheel-rail normal contact pressure and interfacial shear stress distributions, and the stress intensity factors (SIF), are studied for oblique cracks of different inclinations, and the variations in both contact stress distributions near the crack edge are simulated under normal and traction loads, respectively. Contact elements are employed to model the interactions between the wheel-rail contact surfaces and the crack surfaces, respectively. The effects of crack orientation, crack length, and contact distance on the contact stress distributions and stress intensity factors, KI and KII, are investigated. The results indicate that a wheel-rail traction force reduces KII significantly as the contact point travels over the crack edge. Furthermore, fluctuations in KI and KII are very significant with regard to early squat propagation of cracks. The results also demonstrate that applying Carter’s contact model or the full slip contact model to the same wheel-rail contact crack problem yields significantly different stress intensity factor values.
Thermoelastic Problems for the Anisotropic Elastic Half-Plane
Authors: Lin Yuan , Ovaert Timothy C.
Published: June 2004

By applying the extended version of Stroh’s formalism, the two-dimensional thermoelastic problem for a semi-infinite anisotropic elastic half-plane is formulated. The steady-state heat transfer condition is assumed and the technique of analytical continuation is employed; the formulation leads to the Hilbert problem, which can be solved in closed form. The general solutions due to different kinds of thermal and mechanical boundary conditions are obtained. The results show that unlike the two-dimensional thermoelastic problem for an isotropic media, where a simply-connected elastic body in a state of plane strain or plane stress remains stress free if the temperature distribution is harmonic and the boundaries are free of traction, the stress within the semi-infinite anisotropic media will generally not equal zero even if the boundary is free of traction.
Aqueous Extract of Phyllanthus urinaria Induces Apoptosis in Human Cancer Cells
Authors: Huang Sheng-Teng , Yang Rong-Chi , Pang Jong-Hwei S.
Published: June 2004

Cell apoptosis is now known to play an important role in the maintenance of cellular homeostasis and anti-carcinogenesis. The anticancer effect of aqueous extract prepared from Phyllanthus urinaria (P. urinaria) was investigated by analyzing its potential to induce apoptosis in human cancer cells. We showed that the aqueous extract of P. urinaria could reduce the viability by inducing the apoptosis in human cancer cells derived from several different origins as demonstrated by morphological changes and DNA fragmentation. Yet, P. urinaria extract exhibited no cytotoxic effect on normal human cells, including vascular endothelial cells and liver cells under the same conditions. It suggests that the aqueous extract of P. urinaria is substantially useful in treating various kinds of human cancer cells without toxic side effect on normal cells.
Radix Bupleuri Containing Compound (KY88 Liver-Livo) Induces Apoptosis and Production of Interleukin-4 and Tumor Necrosis Factor-α in Liver Cancer Cellsin Vitro
Authors: Chow Louis W.C. , Loo Wings T.Y. , Sham Jonathan S.T. , Cheung Mary N.B.
Published: June 2004

Hepatocellular carcinoma is an important health problem in Asia. A blend of herbal extracts containing radix bupleuri (KY88) was tested for its effects on liver cancer cells. A hepatocellular carcinoma cell line (HB8064) was cultured with methanol extract of KY88. We were able to produce a dose-dependent inhibition of cancer cell proliferation. At IC50and IC100, KY88 induces a DNA ladder pattern, indicating the presence of apoptosis. We also checked the changes of the levels of interleukin (IL)-2, -4 and -6, interferon (INF)-γ and tumor necrosis factor (TNF)-α by ELISA kits. After 24 hours of culture, there was activation of IL-2 and -4 and TNF-α. However, significant changes were observed only for IL-4 and TNF-α. Therefore, we concluded that KY88 is able to induce apoptosis, which may be regulated through changes in IL-4 and TNF-α.
Corticotropin-Releasing Factor and Interleukin-1β are Involved in the Electroacupuncture-Induced Analgesic Effect on Inflammatory Pain Elicited by Carrageenan
Authors: Sekido Reina , Ishimaru Keisou , Sakita Masakazu
Published: June 2004

Electroacupuncture (EA) is used to relieve various kinds of pain. However, the mechanistic basis of electroacupuncture analgesia (EAA) in inflammatory pain remains unclear. In the present study, we investigated whether endogenous peripheral corticotropin-releasing factor (CRF) or interleukin-1β (IL-1) participated in EAA during hyperalgesia elicited by carrageenan-induced inflammation. Carrageenan was subcutaneously administered by intraplantar (i.pl.) injection of the left hind paw to induce inflammation. Nociceptive thresholds were measured using the paw pressure threshold (PPT) (Randall Sellito Test). Rats received 3 Hz EA in the left anterior tibial muscles for 1 hour after carrageenan injection. The selective CRF antagonist, α-helical CRF, or the recombinant IL-1 receptor antagonist, IL-1ra, was administered by i.pl. injection of the inflamed paw or by intravenous (i.v.) injection 1 hour before EA. PPT decreased significantly 3 hours after carrageenan injection. This decrease persisted at least 24 hours after carrageenan injection. EA resulted in significant increases of PPT, moreover, PPT elevations lasted 24 hours after carrageenan injection. By contrast, PPT elevations produced by EA were dose-dependently antagonized by local i.pl. injection of α-helical CRF or IL-1ra. This PPT elevation was not influenced by i.v. injection of α-helical CRF or IL-1ra. These findings suggest that peripheral CRF or IL-1 participate in EAA during hyperalgesia. The release of CRF or IL-1 elicited by EA may trigger the release of opioid peptides within inflamed tissue which may activate peripheral opioid receptors and inhibit the pain.
A Four-Week, Randomized, Double-Blind Trial of the Efficacy and Safety of SKI306X: A Herbal Anti-arthritic Agent versus Diclofenac in Osteoarthritis of the Knee
Authors: Jung Young-Bok , Seong Sang-Cheol , Lee Myung-Chul , Shin Yong-Un , Kim Dong-Han , Kim Jung-Man , Jung Yang-Kuk , Ahn Jin-Hwan , Seo Jai-Gon , Park Youn-Soo , Lee Chong-Suh , Roh Kwon-Jae , Han Chang-Kyun , Cho Yong-Baik , Chang Don-Yong , Kwak Wie-Jong , Jung Kui-Oak , Park Byung-Joo
Published: June 2004

The efficacy and safety of SKI306X, an herbal anti-arthritic agent, was compared with that of diclofenac sodium for the treatment of osteoarthritis of the knee. In a randomized, double-blind, active comparator-controlled trial, a total of 249 patients were randomly assigned to receive either 200 mg of SKI306X three times daily or 100 mg of diclofenac sustained release (SR) once daily. Clinical efficacy variables (visual analog scale, Lesquesne index and global satisfaction score) and adverse events were monitored at baseline and 2nd and 4th weeks of treatment. SKI306X demonstrated efficacy statistically comparable to that of diclofenac, as assessed by the VAS and patients' and investigators' global satisfaction score. Both treatments were well tolerated, however, the SKI306X treatment group experienced less heartburn (4.0% versus 13.7%, p=0.015, chi-square test). In this four-week trial, SKI306X was well tolerated and demonstrated clinical efficacy comparable to that of diclofenac SR.
A STABILIZED SCHEME FOR THE LAGRANGE MULTIPLIER METHOD FOR ADVECTION-DIFFUSION EQUATIONS
Authors: RAPIN GERD , LUBE GERT
Published: June 2004

We consider a new stabilized finite element method for advection-diffusion equations, where the Dirichlet boundary condition is imposed in a weak sense by Lagrange multipliers. The inf–sup condition of the corresponding mixed problem is circumvented by adding some further terms. Using the SUPG-stabilization, an optimal a priori estimate is shown for the singularly perturbed case. Then we present an a posteriori error estimator for our stabilized scheme. Some numerical experiments support the theoretical results. The present results are basic for a nonconforming three-field formulation of the problem.
QUANTUM AND THERMAL CORRECTIONS TO A CLASSICALLY CHAOTIC DISSIPATIVE SYSTEM
Authors: RODRÍGUEZ-ACHACH MANUEL , PÉREZ GABRIEL , CERDEIRA HILDA A.
Published: June 2004

The effects of quantum and thermal corrections on the dynamics of a damped nonlinearly kicked harmonic oscillator are studied. This is done via the quantum Langevin equation formalism working on a truncated moment expansion of the density matrix of the system. We find that the type of bifurcations present in the system change upon quantization and that chaotic behavior appears for values of the nonlinear parameter that are far below the chaotic threshold for the classical model. Upon increase of temperature or Planck's constant, bifurcation points and chaotic thresholds are shifted towards lower values of the nonlinear parameter. There is also an anomalous reverse behavior for low values of the cutoff frequency.
REGULARIZATION OF QUASILINEAR HEAT EQUATIONS BY A FRACTIONAL NOISE
Authors: NUALART DAVID , OUKNINE YOUSSEF
Published: June 2004

We show the existence and uniqueness of a solution for a quasilinear parabolic equation in one dimension driven by an additive fractional white noise, assuming that the drift is measurable and satisfies a suitable integrability condition. The proof is based on Girsanov theorem and lower estimates of the density of the solution of the equation without drift.
DERIVATION ALGEBRAS OF RINGS RELATED TO HEISENBERG ALGEBRAS
Authors: BERGEN JEFFREY
Published: June 2004

In this paper, we will determine the Lie algebra of derivations of rings which are generalizations of the enveloping algebras of Heisenberg Lie algebras. First, we will determine which derivations are X-inner and also determine which elements in the Martindale quotient ring induce X-inner derivations. Then, we will show that the Lie algebra of derivations is the direct sum of the ideal of X-inner derivations and a subalgebra which is isomorphic to a subalgebra of finite codimension in a Cartan type Lie algebra.
UNDERSTANDING PERCEPTIONS OF CHANGE: A PATHWAYS CONTRIBUTION TO COMMUNITY CONSULTATION AND ENVIRONMENTAL DECISION-MAKING
Authors: LEMON MARK , JEFFREY PAUL , MCINTOSH BRIAN S. , OXLEY TIM
Published: June 2004

Participation has become part of the language of environmental management. While this move is positive there remains a danger that overly formalised and restricted participatory procedures, in terms of the information sought, may constrain and hinder dialogue and learning between the public and management agencies. Responses to specific issues are often sought from members of the public without a clear understanding about whether those issues are salient to them, where they are salient or how they fit into multiple and dynamic interpretations of environmental change. This paper uses case study material from the UK to demonstrate a novel Pathways Approach to the recording and analysis of individual perceptions about environmental change. The approach seeks to concentrate on experience and interpretation and is based on the conceptualisation of perceived cause–effect relationships and the pathways that support them. The links between time, space and community are considered within this analysis, as is the potential for improved participation through the provision of policy relevant information to planners and environmental managers operating in complex, multi-perspective situations.
EIA SCREENING FOR CHANGES AND EXTENSIONS TO EXISTING PROJECTS: APPLYING AN EU PERSPECTIVE
Authors: WESTON JOE
Published: June 2004

Directive 97/11/EC, amending the Environmental Impact Assessment (EIA) Directive (85/337/EEC), introduced a number of key changes to the procedures of EIA in the European Union (EU). One significant amendment was the introduction of a requirement for EIAs to be completed for "changes or extensions to Annex I or II projects that have already been authorised executed or are in the process of being executed and which are likely to have significant adverse effects on the environment (CEC, 1997). That requirement imposes a duty on competent authorities to screen all changes and extensions of Annex I and Annex II projects for the need for EIA. Applying legal and policy principles established in the European Union, the scope of what constitute relevant changes and extensions is very wide. Given this wide scope, it would be reasonable to assume that screening changes or extensions would have been a major growth area of EIA activity in the UK. However, evidence presented here indicates just the opposite and suggests that many local planning authorities are not fully aware of the full implications of this clause in the EIA Directive. Furthermore, for the full implications of the "changes and extensions" clause to be implemented in the UK may require further amendments to the EIA legislation.
POTENTIAL BENEFITS OF COMBINING ENVIRONMENTAL MANAGEMENT TOOLS IN A LOCAL AUTHORITY CONTEXT
Authors: EMILSSON SARA , TYSKENG SARA , CARLSSON ANNICA
Published: June 2004

Today, there are many environmental management tools available to support integration of environmental perspectives in decision-making processes. However, a single tool is seldom the answer to all queries. This paper shows potential benefits of using a combination of different environmental management tools in a local authority context. Three environmental management tools used in Swedish local authorities are examined — Substance Flow Analyses (SFA), Strategic Environmental Assessment (SEA), and Environmental Management Systems (EMSs) — from mainly a theoretical point-of-view. The tools are positioned according to their key characteristics, and their individual contribution to environmental management in local authorities is explored. For the local authorities, a combination of tools allows decision-makers to integrate experience from individual projects to overall environmental management, which helps decision-makers to deal with some of the challenges that different environmental management situations require.
DEVELOPMENT OF A LIFE CYCLE ASSESSMENT (LCA) BASED DECISION-MAKING TOOL FOR THE ASSESSMENT OF BUILDING PRODUCTS
Authors: URIE ALEXANDRA , DAGG SUZAN
Published: June 2004

This paper introduces the need for the responsible selection of construction products and then analyses a number of assessment methodologies. Some computer packages and guidebooks that assist in life cycle assessment or aid construction product selection are briefly reviewed. Issues that affect decision-making and complexities in the construction industry are discussed. A tool for assisting responsible construction product selection is then presented that involves carrying out a streamlined life cycle assessment, comparing a novel product to a traditional product. The tool is pragmatic because only three environmental criteria are considered (resource consumption, energy use and human and ecological impacts) and a relative rather then absolute assessment is required. The decision-assisting methodology is demonstrated with a case study. The limitations and benefits of the streamlined LCA are finally presented.
Sliding mode control of a magnetic levitation system
Authors: Al-Muthairi N. F. , Zribi M.
Published: June 2004

Sliding mode control schemes of the static and dynamic types are proposed for the control of a magnetic levitation system. The proposed controllers guarantee the asymptotic regulation of the statesof the system to their desired values. Simulation results of the proposed controllers are given to illustrate the effectiveness of them. Robustness of the control schemes to changes in the parameters of the system is also investigated.
On certain comparison theorems for half‐lineardynamic equations on time scales
Authors: Řehák Pavel
Published: June 2004

We obtain comparison theorems for the second‐order half‐linear
dynamic equation , where
Φ(x) = |x|α−1sgn x with α > 1. In particular,
it is shown that the
nonoscillation of the previous dynamic equation is preserved if
we multiply the coefficient p(t) by a suitable function q(t)
and lower the exponent α in the nonlinearity Φ, under
certain assumptions. Moreover, we give a generalization of
Hille‐Wintner comparison theorem. In addition to the aspect of
unification and extension, our theorems provide some new results
even in the continuous and the discrete case.
On linear singular functional‐differential equationsin one functional space
Authors: Shindiapin Andrei
Published: June 2004

We use a special space of integrable functions for studying the
Cauchy problem for linear functional‐differential equations with
nonintegrable singularities. We use the ideas developed by
Azbelev and his students (1995). We show that by
choosing the function ψ
generating the space, one can
guarantee resolubility and certain behavior of the solution near
the point of singularity.
Progression of a General Substance Use Pattern among Adolescents in Switzerland? Investigating the Relationship between Alcohol, Tobacco, and Cannabis Use over a 12-Year Period
Authors: Kuntsche Emmanuel N.
Published: June 2004

Many studies have shown that different risk or problem behaviors in adolescence are interrelated. Given the increased use of various substances among adolescents in the United States and in most European countries, the question emerges whether there are more substance use ‘specialists’ or a progression of a general substance use pattern. If the latter is the case, the interrelatedness of the different substances should remain stable over time in a representative sample and among subgroups characterized by gender and language. Data from 4,146 15-year-olds in Switzerland surveyed in 1986, 1994 and 1998 were analyzed, using confirmatory factor analyses based on polychoric correlations. Smoking, drunkenness and cannabis use greatly increased over the 12-year period. However, in the different survey years, the factor structure did not differ for all 15-year-olds in general or for subgroups. This progression of a general pattern refers to an increased normalization of recreational substance use in general, not only of cannabis use. Favorable attitudes towards general substance use are a challenge to substance use prevention in adolescence, and reveal a need for more research on such a progression in other countries.
Readiness to Change in a Clinical Sample of Problem Drinkers: Relation to Alcohol Use, Self-Efficacy, and Treatment Outcome
Authors: Demmel Ralf , Beck Beate , Richter Dirk , Reker Thomas
Published: June 2004

According to the transtheoretical model of behaviour change, individuals addicted to psychotropic drugs typically cycle through a sequence of five discrete stages (precontemplation, contemplation, preparation, action, and maintenance) before achieving sustained long-term abstinence and moderation, respectively. A number of English-language questionnaires have been developed to assess client motivation in accordance with the stages of change approach. The present study aimed to expand the research on the transtheoretical model by establishing the factor structure of a German-language version of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) in a large sample of alcohol-dependent inpatients (n = 350). Furthermore, the relation of client motivation to alcohol use, self-efficacy and treatment outcome at 3-month follow-up was examined. Exploratory factor analysis revealed three separate dimensions of readiness to change (Taking Steps, Recognition, and Ambivalence). The factorial structure of the German-language SOCRATES corresponded almost exactly to that of the original version. Readiness to change accounted for 9.4% of the variance in treatment outcome. Moreover, readiness to change was positively related to pretreatment self-efficacy.
Pharmacodynamics and Bactericidal Activity of Gatifloxacin in Experimental Pneumonia Caused by Penicillin-Resistant Streptococcus pneumoniae
Authors: Yanagihara Katsunori , Fukuda Yuichi , Miyazaki Yoshitsugu , Tsukamoto Kazuhiro , Hirakata Yoichi , Tomono Kazunori , Kadota Jun-Ichi , Tashiro Takayoshi , Murata Ikuo , Kohno Shigeru
Published: June 2004

Background: Antimicrobial resistance rates for Streptococcus pneumoniae continue to increase worldwide, and resistance to nearly every major class of antimicrobials used to treat pneumococcal infections has been reported. Gatifloxacin (GFLX) is one of the quinolones that have strong activity against S. pneumoniae.Methods: We compared the bacteriological, pharmacological and histopathological effects of orally administered GFLX with those of levofloxacin (LVFX) and ciprofloxacin (CPFX) in a murine model of pneumonia caused by penicillin-resistant S. pneumoniae (PRSP). Results: Treatment with GFLX resulted in a significant decrease in the number of viable bacteria (control, CPFX, LVFX, and GFLX: 6.48 ± 0.36, 6.44 ± 0.27, 5.51 ± 0.15, and 4.89 ± 0.28 log10 CFU/lung, respectively, mean ± SD). A significant decrease in mortality was observed in the GFLX-treated group in comparison with the other groups. Histopathological examination revealed that inflammatory changes in GFLX-treated mice were less marked than in the other mice. Conclusion: Our results suggest that orally administered GFLX is effective in PRSP pneumonia. The pharmacokinetic profiles also reflected the effectiveness of GFLX.
A New Perspective on Cardiotoxicity of 5-Fluorouracil
Authors: Barutca Sabri , Ceyhan Ceyhun , Meydan Nezih , Ozturk Banu , Tekten Tarkan , Onbasili Alper , Kadikoylu Gurhan , Bolaman Zahit
Published: June 2004

Background: The pathophysiology of 5-fluorouracil (5-FU) cardiotoxicity is still controversial. The objective of this study was to assess the influence of high-dose leucovorin and infusional 5-FU regimen (HDLV5FU) on cardiac tissues. Methods: We monitored 28 patients (median age 68 years) under HDLV5FU chemotherapy with complete blood counts, cardiac enzymes, C-reactive protein, coagulation tests, Holter electrocardiogram, and conventional echocardiography. Cardiac ultrasonic tissue characterization with integrated backscatter (IBS) analysis was performed in the 16 last enrolled patients. Results: The magnitude of both anterior and posterior cardiac IBS values significantly decreased at the 48th hour of treatment compared to both 0th hour and day 15 (p < 0.003). Cardiac IBS values on the 15th day were not different from the 0th hour. Clinical cardiotoxicity was not observed and other monitored parameters did not change significantly in any patient (p > 0.5 for all). Conclusion: Cardiac IBS analysis suggests that 5-FU might cause reversible subclinical myocardial dysfunction.
Hypoxia-Inducible Factor 1alpha- Mediated Resistance to Phenolic Anticancer
Authors: Hyun Ju-Yeon , Chun Yang-Sook , Kim Tae-You , Kim Hye-Lim , Kim Myung-Suk , Park Jong-Wan
Published: June 2004

Background: Phenolic compounds EGCG [(–)-epigallocatechin-3-gallate], resveratrol (3,4′,5-trihydroxy-trans-stilbene) and capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) are worth investigating for clinical application in cancer prevention and chemotherapy. Hypoxia-induced drug resistance is a major obstacle in the development of effective cancer chemotherapy. Therefore, we examined whether drug resistance to these phenolic compounds is acquired by hypoxia. Methods: Hep3B hepatoma, Caki-1 renal carcinoma, SK-N-MC neuroblastoma, and HEK293 cell lines were cultured under normoxic or hypoxic conditions. Drug sensitivities to the phenolic compounds and expression of hypoxia-inducible factor-1α (HIF-1α) and the multidrug resistance genes were examined in these cell lines. Results: Drug resistance was acquired 24 h after hypoxia and subsided 8 h after reoxygenation. Protein synthesis inhibitors abolished this drug resistance. A transfection study demonstrated that HIF-1α enhanced this hypoxia-induced resistance and that its dominant-negative isoform suppressed resistance acquisition. However, MDR1 and MRP1, which provide multidrug resistance to conventional anticancer agents, were not induced by hypoxia. Conclusions: These results suggest that HIF-1α-dependent gene expression participates in the cellular process of the hypoxia-induced resistance to phenolic compounds.
Chemotherapy Delays Progression of Motor Neuron Disease in the SOD1 G93A Transgenic Mouse
Authors: Bruce K.M. , Narayan K. , Kong H.C. , Larmour I. , Lopes E.C. , Turner B.J. , Bertram J.F. , Cheema S.S.
Published: June 2004

Background: A significant proliferation of glial cells occurs in the spinal cord and brainstem of SOD1 G93A transgenic mice with familial amyotrophic lateral sclerosis (ALS). Since activated glia may contribute to motor neuron degeneration, we tested whether inhibition of gliosis using low-dose chemotherapy is beneficial in this mouse model. Methods: Mice were administered fortnightly intraperitoneal injections of 0.1 mg/kg vincristine (VIN) or saline commencing at postnatal day 68 before disease onset. Mice were sacrificed at end-stage disease, and spinal cords were examined for histology. Results: Survival of VIN-treated mice was significantly increased at 132.0 ± 4.1 days compared to control animals at 117.8 ± 2.1 days (p < 0.05). Furthermore, analysis of microglia and astrocyte populations suggests a reduction in the former following VIN therapy. Conclusion: This study suggests that chemotherapy may offer an alternative therapy or co-therapy for ALS.
Synergism of Ciprofloxacin and Trimethoprim against Salmonella enterica Serovar typhi Isolates Showing Reduced Susceptibility to Ciprofloxacin
Authors: Mandal Shyamapada , Mandal Manisha Deb , Pal Nishith Kumar
Published: June 2004

The activity of the combination of ciprofloxacin and trimethoprim against 16 Salmonella enterica serovar typhi isolates from blood cultures were tested by agar dilution checkerboard technique. When used in combination, minimum inhibitory concentrations (MICs) of ciprofloxacin and trimethoprim ranged from 0.5 to 1.25 and from 10 to 125 µg/ml, respectively, and fractional inhibitory concentrations (FICs) from 0.025 to 0.125 and from 2.5 to 10 µg/ml, respectively. The FIC index was 0.140–0.483, indicating a marked synergy between ciprofloxacin and trimethoprim against trimethoprim-resistant S. enterica serovar typhi isolates (100%) with high MICs for ciprofloxacin.
Endothelin-1 Is Increased in the Breath Condensate of Patients with Non-Small-Cell Lung Cancer
Authors: Carpagnano G.E. , Foschino-Barbaro M.P. , Resta O. , Gramiccioni E. , Carpagnano F.
Published: June 2004

One recent line of cancer research is currently directed to the study of growth factors. Of increasing interest is endothelin-1 (ET-1), a mitogenic factor already investigated in several human cancer cell lines, which has been found to participate in the development and progression of tumours. This peptide has an important role also in non-small-cell lung cancer (NSCLC) where ET-1 expression has been found in 100% of cell lines. Objectives: The aim of this study was to measure ET-1 concentrations in the airways of patients with NSCLC using a completely non-invasive procedure – the breath condensate – and to verify the involvement of this peptide in the growth of lung tumours. Methods: We enrolled 30 patients (17 men, median age 63 years; range 53–74) with histological evidence of NSCLC and 15 healthy controls (9 men, median age 59 years; range 52–70). ET-1 was measured in the exhaled breath condensate by means of a specific enzyme immunoassay kit. Results: Higher concentrations of exhaled ET-1 were found in NSCLC patients (8.3 ± 0.7 pg/ml) compared to controls (5.2 ± 0.5 pg/ml, p < 0.0001). A statistically significant difference was observed between patients with distant metastases (stage IV) of NSCLC (8.9 ± 0.6 pg/ml) and those with locoregional disease (stage I–III) (7.9 ± 0.5 pg/ml). A significant reduction in ET-1 levels was found in 14 patients after surgical removal of the tumour either associated with or without adjuvant chemotherapy (6.3 ± 0.5 vs. 7.9 ± 0.4 pg/ml, p < 0.0001). Conclusions: These findings suggest that the measurement of ET-1 in the breath condensate of patients with NSCLC could be proposed as a marker for early detection of NSCLC as well as for monitoring reduction or progression of the neoplasm in the follow-up of treated patients.
Paclitaxel, Epirubicin and Cyclophosphamide Combination in First-Line Treatment of Metastatic Breast Cancer: A Dose Escalation Study
Authors: Bonneterre Jacques , Tubiana-Hulin Michèle , Catimel Gilles
Published: June 2004

The purpose of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of combined paclitaxel, epirubicin and cyclophosphamide in patients with metastatic breast cancer. The dose of paclitaxel was planned to be escalated from 150 to 225 mg/m2 in 25 mg/m2 steps, while the doses of epirubicin and cyclophosphamide were fixed at 50 and 500 mg/m2, respectively. Because of DLT, the dose of paclitaxel was maintained at 200 mg/m2 and the dose of epirubicin was increased to 90 mg/m2. The MTD was reached at a dose of paclitaxel and epirubicin of 200 and 75 mg/m2,respectively. DLT were mainly febrile neutropenia and grade 4 neutropenia lasting for ≧7 days. Among the 35 evaluable patients, there were 2 (6%) complete responses and 19 (53%) partial responses for an overall response rate of 59% [95% confidence interval (CI): 41–74%]. The triplet paclitaxel/epirubicin/cyclophosphamide is an effective and well-tolerated combination worthy of further investigation in the treatment of patients with metastatic breast cancer.
A Multicenter Phase II Study of the Combination of Irinotecan and Gemcitabine in Previously Treated Patients with Small-Cell Lung Cancer
Authors: Agelaki Sofia , Syrigos Kostas , Christophylakis Charalambos , Boukovinas John , Varthalitis John , Pavlakou Georgia , Athanasiadis Athanasios , Kouroussis Charalambos , Vardakis Nikolaos , Maltezakis George , Milaki Georgia , Georgoulias Vassilis
Published: June 2004

Objective: To evaluate efficacy and toxicity of the combination of irinotecan and gemcitabine in pretreated patients having small-cell lung cancer. Patients andMethods: Thirty-one patients (median age 60 years, performance status 0–1 in 87% and 2 in 13% of the patients) with limited or extensive-stage disease, refractory or relapsing after at least one prior chemotherapy regimen, received gemcitabine 1,000 mg/m2 on days 1 and 8 and irinotecan 300 mg/m2 on day 8, every 21 days. Sixteen (52%) patients had sensitive and 15 (48%) refractory disease. Fifteen patients (48%) had received ≧2 prior regimens. Results: All patients were evaluable for toxicity and 26 for response analysis. A median of three (range 1–6) cycles per patient was administered. Three partial responses were documented for an overall response rate of 10% (95% CI 0.73–20.09), and disease stabilization was obtained in 7 patients (22%; intention-to-treat analysis). Two of the responders had refractory, and 1 had sensitive disease. The median time to progression was 4.5 months, the median duration of responses was 2.5 months, and the median survival time was 6 months. Grade 3–4 (WHO) neutropenia was observed in 9 patients (29%), grade 3–4 thrombocytopenia in 4 (13%), and grade 3–4 diahrrea in 3 patients (10%). Three patients experienced febrile neutropenia. No toxic deaths occurred. Conclusions: The combination showed modest activity in this patient group with a poor prognosis. Thus we believe it merits further investigation in the treatment of patients with small-cell lung cancer who have failed one prior chemotherapy regimen.
Gemcitabine and Cisplatin in Refractory Malignant Lymphoma
Authors: Avilés Agustín , Neri Natividad , Huerta-Guzmán Judith , Fernández Raúl
Published: June 2004

Objective: We performed a pilot study to evaluate the effect of the high-dose gemcitabine-cisplatin combination in a brief weekly regimen in the treatment of primary refractory diffuse large cell lymphoma with high or high-intermediate clinical risk. Methods: Thirty patients refractory to first-line anthracycline-based chemotherapy were treated with a combination of gemcitabine (1.5 g/m2 i.v.) and cisplatin (50 mg/m2 i.v.) on days 1, 8, 22, 29, 42 and 49. No further treatment was administered. Results: Complete response rate was 53%; and only two relapses have been observed at the last follow-up. Thus actuarial disease-free survival at the 3-year follow-up was: 87% (95% confidence interval, CI: 70–93%) and overall survival 53% (95% CI: 44–63%). Toxicity was mild, and treatment was well tolerated. No treatment-related death was observed. Conclusions: The gemcitabine-cisplatin combination appears to be promising in the treatment of refractory lymphoma patients, with a low toxicity. However, a longer follow-up is needed to confirm the results. In our opinion, prolonged chemotherapy (6–8 cycles) did not improve outcome. At present, we are testing if the use of monoclonal antibodies (anti-CD20) employed as maintenance therapy may improve disease-free survival and overall survival.
Caspase-3 Expression in Human Gastric Carcinoma and Its Clinical Significance
Authors: Isobe Naoki , Onodera Hisashi , Mori Akira , Shimada Yutaka , Yang Weige , Yasuda Seiichi , Fujimoto Akihisa , Ooe Hideaki , Arii Shigeki , Kitaichi Masanori , Imamura Masayuki
Published: June 2004

Objectives: Caspase-3 is one of the most important molecules in the apoptosis cascade, and the relationship between caspase-3 expression and prognosis has been reported in many types of malignancies. However, the involvement of caspase-3 in human gastric carcinoma is not fully understood. We evaluated caspase-3 expression in human gastric carcinoma to clarify the clinicopathological importance and investigated the apoptosis avoidance mechanism by an immunohistological method. Methods: Specimens from 151 patients who underwent gastrectomy at the Department of Surgery and Surgical Basic Science of Kyoto University Hospital were investigated. Caspase-3 expression in cancer cells was evaluated by comparing its expression in the germinal center of the lymphoid follicle, and was quantified as the caspase-3 expression index (C3EI). C3EI was compared with the expression of Bcl-2 and the TdT-mediated dUTP biotin nick-end labeling (TUNEL) in 80 randomly selected cases. Actual activation of caspase-3 was determined by immunohistochemistry using monoclonal antibody that recognizes only activated caspase-3. Results: C3EI correlated significantly with lymph node metastasis (negative 105.5–78.7, positive 153.8 ± 66.1 p = 0.001) and the lower C3EI group had a better prognosis than the higher group (log-rank test, p = 0.0001). Cox multivariate analysis showed that age, operation curability, tumor invasion and C3EI were significant independent determinants of overall survival. Bcl-2 and TUNEL staining had no significant correlations with C3EI. Immunohistochemistry of activated caspase-3 revealed that most caspase-3 in gastric cancer cells was not activated, in accordance with TUNEL assay. Conclusions: Our results show that C3EI is a novel, independent prognostic factor in gastric cancer patients and cancer cells may avoid apoptosis by inhibiting caspase-3 activation.
Establishment of a New Cell Line with Neuronal Differentiation Derived from Small Cell Neuroendocrine Carcinoma of the Maxillary Sinus
Authors: Noguchi Kazuma , Urade Masahiro , Kishimoto Hiromitsu , Kuroda Junko , Moridera Kuniyasu , Sakurai Kazunari
Published: June 2004

Objective: It is well known that small cell neuroendocrine carcinoma (SNEC) arising at extrapulmonary sites has a poor prognosis and an interesting biological characterization. To understand biological characterization and elucidation of the origin of the histogenesis of SNEC, we report the establishment of a new SNEC cell line and characteristics of neuroendocrine properties including neuronal differentiation by treatment with dibutyryl cyclic AMP (db-cAMP). Methods: We established a new cell line (SNEC-MI) derived from SNEC of the maxillary sinus by a modified spill-out method, and verified neuroendocrine properties including neuronal differentiation by immunocytochemical and immunoblotting methods. Results: The established cell line showed spherical or spindle shape in monolayer culture and was positive for neuron-specific enolase (NSE), neuronal cell adhesion protein (N-CAM, CD56) and gastrin-releasing peptide. NSE was also demonstrated in the cultured medium and dense-core neuroendocrine granules were detected ultrastructurally in the cytoplasm. Treatment of cells with db-cAMP markedly induced the development and elongation of neuronal processes, which formed a netlike arrangement. Characterization of these elongated neuronal processes revealed them immunoreacting intensely with high molecular-weight neurofilament, and a time-dependent increase of microtubule-associated protein-2 in cell lysates. Conclusions: These findings indicated that this cell line possesses the capability to differentiate into neuronal cells, and supported the hypothesis that extrapulmonary SNEC might be derived from a pluripotent stem cell.
Dietary Supplementation of the Citrus Antioxidant Auraptene Inhibits N,N-Diethylnitrosamine-Induced Rat Hepatocarcinogenesis
Authors: Sakata Keiko , Hara Akira , Hirose Yoshinobu , Yamada Yasuhiro , Kuno Toshiya , Katayama Masaki , Yoshida Koujiro , Zheng Qiao , Murakami Akira , Ohigashi Hajime , Ikemoto Kohei , Koshimizu Koichi , Tanaka Takuji , Mori Hideki
Published: June 2004

Objectives: We have previously reported that an antioxidant, auraptene (AUR), isolated from citrus fruit effectively inhibits chemically induced carcinogenesis in digestive tracts, such as the oral cavity, esophagus and large bowel. In this study, we investigated the modifying effects of dietary supplementation with AUR on N,N-diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in male F344 rats in two different experiments to determine whether the compound exerts a cancer-chemopreventive action in other organs. Methods: In the first experiment, animals were fed diets containing AUR at dose levels of 100 and 500 ppm for 7 weeks 1 week before, during, and 1 week after the start of liver carcinogenesis induced by DEN (40 ppm in drinking water for 5 weeks) to predict the modulatory effect on hepatocarcinogenesis. After 7 weeks, the numbers of hepatocellular enzyme-altered foci (EAF; cm2) which stained positive for the placental form of glutathione S-transferase (GST-P) and transforming growth factor (TGF)-α were determined on immunohistochemically stained sections. In the second experiment conducted to confirm the findings, animals subjected to DEN treatment were fed AUR-containing diets (100 and 500 ppm) during either the initiation stage (‘initiation’ feeding for 7 weeks) or post-initiation phase (‘post-initiation’ feeding for 25 weeks) of DEN-induced hepatocarcinogenesis. Results: In the first experiment, feeding with AUR at both doses during DEN exposure decreased the mean numbers of GST-P-positive and TGF-α-positive EAF/cm2, and the reduction in the number of TGF-α-positive EAF by feeding 500 ppm AUR was statistically significant (p < 0.005). In the second experiment, the ‘initiation’ feeding with 500 ppm AUR significantly inhibited the incidence (33 vs. 83%, p = 0.000511) and multiplicity (0.67 ± 1.09 vs. 1.96 ± 1.85, p < 0.005) of liver cell carcinoma. Also, the ‘post-initiation’ feeding with AUR at both doses significantly reduced the development of hepatocellular carcinoma (100 ppm: incidence, 15%, p = 0.000006; multiplicity: 0.25 ± 0.64, p < 0.001; 500 ppm: incidence, 11%, p = 0.000002; multiplicity, 0.26 ± 0.81, p < 0.001). In addition, AUR feeding reduced cell proliferation and the apoptotic index in liver cell neoplasms. Conclusions: The results suggest that the citrus antioxidant AUR is a potential chemopreventive agent against DEN-induced hepatocarcinogenesis in rats.