bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinguishing enzymes using metabolome data for the hybrid dynamic/static method
Authors: Ishii Nobuyoshi , Nakayama Yoichi , Tomita Masaru 
Published: May 2007

Abstract

Background
In the process of constructing a dynamic model of a metabolic pathway, a large number of parameters such as kinetic constants and initial metabolite concentrations are required. However, in many cases, experimental determination of these parameters is time-consuming. Therefore, for large-scale modelling, it is essential to develop a method that requires few experimental parameters. The hybrid dynamic/static (HDS) method is a combination of the conventional kinetic representation and metabolic flux analysis (MFA). Since no kinetic information is required in the static module, which consists of MFA, the HDS method may dramatically reduce the number of required parameters. However, no adequate method for developing a hybrid model from experimental data has been proposed.

Results
In this study, we develop a method for constructing hybrid models based on metabolome data. The method discriminates enzymes into static modules and dynamic modules using metabolite concentration time series data. Enzyme reaction rate time series were estimated from the metabolite concentration time series data and used to distinguish enzymes optimally for the dynamic and static modules. The method was applied to build hybrid models of two microbial central-carbon metabolism systems using simulation results from their dynamic models.

Conclusion
A protocol to build a hybrid model using metabolome data and a minimal number of kinetic parameters has been developed. The proposed method was successfully applied to the strictly regulated central-carbon metabolism system, demonstrating the practical use of the HDS method, which is designed for computer modelling of metabolic systems.
Femoral tunnel placement in anterior cruciate ligament reconstruction: rationale of the two incision technique
Authors: Garofalo Raffaele , Moretti Biagio , Kombot Cyril , Moretti Lorenzo , Mouhsine Elyazid 
Published: May 2007

Abstract
Endoscopic anterior cruciate ligament (ACL) reconstruction can be performed through one-incision or two-incision technique. The current one-incision endoscopic ACL single bundle reconstruction techniques attempt to perform an isometric repair placing the graft along the roof of the intercondylar notch, anterior and superior to the native ACL insertion. However the ACL isometry is a theoretical condition, and has not stood up to detailed testing and investigation. Moreover this type of reconstruction results in a vertically oriented non-anatomic graft, which is able to control anterior tibial translation but not the rotational component of the instability. Femoral tunnel obliquity has a great effect on rotational stability. To improve the obliquity of graft, an anatomical ACL reconstruction should be attempt. Anatomical insertion of ACL on the femur lies very low in the notch, spreading between 11 and 9–8 o'clock position and the center lies lower than at 11 o'clock position. Femoral aiming devices through the tibial tunnel aim at an isometric placement, and they do not aim at an anatomic position of the graft. Also, a placement of tunnel in a position of 11 o'clock is unable to restore rotational stability. The two-incision technique, with the possibility to position femoral tunnel independently by tibial tunnel, allows us to place femoral tunnel entrance in a position of 10 'clock that can most accurately reproduce the anatomic behaviour of the ACL and can potentially improve the response of the graft to rotatory loads. This positioning results in a more oblique graft placement, avoiding problem related to PCL impingement during knee flexion. Further studies are required to understand if this kind of reconstruction can ameliorate proprioception as well as clinical outcome at a long-term follow-up.
Phase I/II Study of an Anti-CD30 Monoclonal Antibody (MDX-060) in Hodgkin's Lymphoma and Anaplastic Large-Cell Lymphoma
Authors: Ansell Stephen M. , Horwitz Steven M. , Engert Andreas , Khan Khuda Dad , Lin Thomas , Strair Roger , Keler Tibor , Graziano Robert , Blanset Diann , Yellin Michael , Fischkoff Steven , Assad Albert , Borchmann Peter 
Published: May 2007

PurposeMDX-060 is a human anti-CD30 immunoglobulin (Ig) G1κ monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed.Patients and MethodsIn the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients—16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma—were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg.ResultsMDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment.ConclusionMDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.
Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma at the Time of Second or Subsequent Remission: Long-Term Follow-Up
Authors: Rohatiner Ama Z.S. , Nadler Lee , Davies Andrew J. , Apostolidis John , Neuberg Donna , Matthews Janet , Gribben John G. , Mauch Peter M. , Lister T. Andrew , Freedman Arnold S. 
Published: May 2007

Purpose The aim of this retrospective analysis was to determine the outcome of patients with follicular lymphoma who received myeloablative therapy supported by autologous bone marrow transplantation as consolidation of second or subsequent remission, with a minimum follow-up of 12 years. Patients and Methods One hundred twenty-one adults received cyclophosphamide (CY) and total-body irradiation (TBI) supported by autologous bone marrow transplantation, with the marrow mononuclear cell fraction having been treated with monoclonal antibodies and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer Institute were combined for the purpose of this analysis because the patients were treated in an identical manner. Results Fifty-seven patients are alive, 41 without progression between 9 and 19 years; 64 patients have died, 20 without progression. With a median follow-up of 13.5 years, 60 patients have developed recurrent lymphoma. There is an apparent plateau on the remission duration curve at 48% at 12 years. Survival of patients treated in second remission was significantly longer than the survival of patients treated later in the course of the illness. Both remission duration and overall survival were also significantly longer for patients treated in second remission compared with an age-matched, remission-matched group of patients treated at St Bartholomew's Hospital before the introduction of this treatment. However, use of CY+TBI was associated with a significant risk of secondary myelodysplasia and secondary acute myeloblastic leukemia, resulting in 15 patient deaths. Conclusion These mature data confirm that prolonged freedom from recurrence may be achieved with myeloablative therapy and that a plateau on the curve seems to emerge with long follow-up.
Tamoxifen, Soy, and Lifestyle Factors in Asian American Women With Breast Cancer
Authors: Wu Anna H. , Pike Malcolm C. , Williams Lee D. , Spicer Darcy , Tseng Chiu-Chen , Churchwell Mona I. , Doerge Daniel R. 
Published: May 2007

PurposeSoy foods have been a staple in Asia for centuries but the consumption of this food in the West is recent. Intake of soy among women at high risk for or with breast cancer has become a public health concern because genistein, a major component of soy, has weak estrogenic effects on breast epithelium, and has been found to negate the benefit of tamoxifen in some animal and in vitro studies.Patients and MethodsWe conducted a cross-sectional study in Asian Americans with breast cancer who were tamoxifen users (n = 380) to investigate the association between soy intake and circulating levels of tamoxifen and its metabolites (N-desmethyl tamoxifen [N-DMT], 4-hydroxytamoxifen [4-OHT], and 4-hydroxy-N-desmethyl-tamoxifen [endoxifen]).ResultsSerum levels of tamoxifen or its metabolites were unrelated to self-reported intake of soy or serum levels of isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women age 65 or older compared with premenopaual women age 45 or younger (P = .005); similar patterns of results were observed for the tamoxifen metabolites. Levels of N-DMT were 27% (P = .03) lower among women in the highest tertile of body mass index (BMI, > 24.4 kg/m2) compared with those in the lowest category (BMI ≤ 21.5). Women who used hypertensive medications had higher levels of tamoxifen (P = .02) and N-DMT (P = .04) compared with nonusers.ConclusionWe found no evidence that soy intake adversely affected levels of tamoxifen or its metabolites. However, age, menopausal status, BMI, and use of hypertensive medications significantly influenced circulating levels of tamoxifen and its metabolites in this population.
The use of proteomics to identify novel therapeutic targets for the treatment of disease
Authors: Moseley Fleur L , Bicknell Katrina A , Marber Michael S , Brooks Gavin 
Published: May 2007

Abstract
The completion of the Human Genome Project has revealed a multitude of potential avenues for the identification of therapeutic targets. Extensive sequence information enables the identification of novel genes but does not facilitate a thorough understanding of how changes in gene expression control the molecular mechanisms underlying the development and regulation of a cell or the progression of disease. Proteomics encompasses the study of proteins expressed by a population of cells, and evaluates changes in protein expression, post-translational modifications, protein interactions, protein structure and splice variants, all of which are imperative for a complete understanding of protein function within the cell. From the outset, proteomics has been used to compare the protein profiles of cells in healthy and diseased states and as such can be used to identify proteins associated with disease development and progression. These candidate proteins might provide novel targets for new therapeutic agents or aid the development of assays for disease biomarkers. This review provides an overview of the current proteomic techniques available and focuses on their application in the search for novel therapeutic targets for the treatment of disease.
Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops
Authors: Loftsson Thorsteinn , Hreinsdóttir Dagný , Stefánsson Einar 
Published: May 2007

Abstract
Delivery of steroids to the retina is currently undertaken with invasive injections into the vitreous cavity. This paper describes a non-invasive method to deliver steroids in therapeutic levels to the retina in rabbits. Dexamethasone was formulated as somewhat water-soluble dexamethasone/γ-cyclodextrin (γCD) microparticles in a low-viscosity aqueous eye drop suspension. The mean (± standard deviation) diameter of the particles was 20.4 ± 10.3 μm, with no particles larger than 60 μm. The aqueous suspension formulation was tested in rabbits and compared with an aqueous dexamethasone eye drop solution containing randomly methylated β-cyclodextrin (RMβCD). The dexamethasone concentration was identical in both formulations (15 mg mL−1). The drug was administered to the left eye but determined in both eyes. The amount reaching different eye tissues via the topical route was determined by subtracting the amount found in the right eye from the amount found in the left eye. Two hours after single application of the dexamethasone/γCD eye drops to rabbits the mean (± s.d.) concentration in vitreous was 29 ± 16 ng g−1, 86% of which reached vitreous via the topical route and in retina the concentration was 57 ± 22 ng g−1 (49% via topical route). For the RMβCD the values were 22.6 ± 9 and 66 ± 49 ng g−1 (73 and 14% via topical route), respectively. These steroid levels are comparable with the dexamethasone concentration achieved 1 month after intravitreal injection. The aqueous dexamethasone/γCD eye drop formulation was chemically stable during 7 months storage and well tolerated with no visible short-term side effects.
Analysis of eupatilin-human serum albumin interactions by means of spectroscopic and computational modelling
Authors: Tang Jianghong , Lian Ning , Bi Chenglu , Li Weihua 
Published: May 2007

AbstractThe interaction of eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone) with human serum albumin (HSA) was studied at simulative physiological pH, with a HSA concentration of 3.0 times 10−6 mol L−1 and eupatilin concentrations over the range of 6.0 times 10−6 to 1.9 times 10−5 mol L−1. Fluorescence spectroscopy in combination with UV absorption spectroscopy and Fourier transform infrared (FTIR) spectroscopy were used to study the binding properties (including binding mechanism, the binding constants, the number of binding sites and the binding mode) of the interaction of eupatilin with HSA and the effect of this drug on HSA conformation changes. According to the Scatchard equation there was only one class of binding site that could bind to HAS; the binding constants were 1.53 times 105, 1.20 times 105, 1.05 times 105, 0.87 times 105 L mol−1 at temperatures of 287, 298, 310 and 318 K, respectively. The FTIR spectra revealed that the protein secondary structure changed, with reductions in α-helices of about 3.65% at a drug to protein molar ratio of 3. The thermodynamic analysis (enthalpy and entropy change: ΔH0 and ΔS0) and the computational modelling study indicated that hydrophobic force played an important role in eupatilin-HSA complex stabilization, and eupatilin could bind within the subdomain IIA of HSA.
Physicochemical characterization of solid dispersions of three antiepileptic drugs prepared by solvent evaporation method
Authors: Douroumis Dionysios , Bouropoulos Nikolaos , Fahr Alfred 
Published: May 2007

Abstract
We have investigated the solid dispersion and dissolution profiles of three antiepileptic drugs (carbamazepine (CBZ), oxcarbazepine (OXC) and rufinamide (RFN)) with different aqueous solubilities, prepared by the solvent evaporation method. Solid dispersions of the three drugs in hydroxy-propylmethylcellulose (HPMC), with drug:polymer ratios of 1:4, were prepared and characterized by differential scanning calorimetry (DSC), Fourier transformation infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy. The release mechanism was also investigated and the kinetic order of the solid dispersions was evaluated. It appeared that the dissolution behaviour depended on the physicochemical properties of the drug and drug-polymer interactions. DSC thermographs showed amorphous forms for all drugs confirmed by XRD patterns. The FTIR spectra of CBZ and OXC demonstrated drug interactions with HPMC through hydrogen polymer bonds. Thus, solid dispersions of these drugs had an improved dissolution profile. In contrast, solid dispersions of RUF showed modest enhancement of dissolution, suggesting negligible drug-polymer interactions. The different dissolution behaviour is attributed to the extent of interactions between the polymer hydroxyl group and the drug amide groups.
Preparation, characterization and pharmacokinetics of N-palmitoyl chitosan anchored docetaxel liposomes
Authors: Liang Ge , Jia-Bi Zhu , Fei Xiong , Bin Ni 
Published: May 2007

Abstract
The objective of this work was to investigate the preparation, characterization and pharmacokinetics of N-palmitoyl chitosan anchored docetaxel liposomes. To decrease toxic effects and improve anti-tumour efficacy of the drug, docetaxel has been incorporated in liposomes; the formulation, stability and pharmacokinetics of plain docetaxel liposomes (PDLs), PEGylated docetaxel liposomes (PEGDLs) and N-palmitoyl chitosan anchored docetaxel liposomes (NDLs) were compared. NDL was more stable than PDL and PEGDL in-vitro, especially in the presence of serum at 37°C. The concentration of docetaxel in the plasma of rats after intravenous administration of docetaxel injection, PDL, PEGDL and NDL was studied by RP-HPLC. The pharmacokinetic behaviour of docetaxel injection, PDL, PEGDL and NDL were significantly different. These findings suggest that anchored liposomes could increase the stability of docetaxel in-vivo, as compared with plain liposomes, but the improvement was not more significant than PEGylated liposomes. N-Palmitoyl chitosan as a new polymeric membrane to anchor liposome was useful to stabilize liposomes containing anti-tumour drug.
Synthesis and pharmacological investigation of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents
Authors: Alagarsamy Veerachamy , Dhanabal Kumarasamy , Parthiban Periyasamy , Anjana Gobi , Deepa Govinhan , Murugesan Balakrishnan , Rajkumar Subramanian , Beevi Abdulrahim Janath 
Published: May 2007

Abstract
A variety of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one was synthesized from 3-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. Compound 2-(1-ethylpropylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS2) was the most active analgesic agent. Compound 2-(1-methylbutylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS3) was the most active anti-inflammatory agent and was moderately more potent than the reference standard diclofenac sodium. The test compounds showed only mild ulcerogenic potential compared with aspirin.
Inhibition of intermediate-conductance Ca2+-activated K+ channel and cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol
Authors: Shen Ai-Yu , Tsai Jen-Hsiang , Teng Hsiu-Chen , Huang Mei-Han , Wu Sheng-Nan 
Published: May 2007

Abstract
The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (IK) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 μM. Neither iberiotoxin (200 nM) nor paxilline (1 μM) suppressed the amplitude of IK, whereas clotrimazole (5 μM) significantly inhibited it. In the inside-out configuration of single channel recordings, application of THPI (5 μM) into the bath medium did not alter the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IKCa) channels (i.e KCa3.1 channels), but it suppressed the channel activity significantly. THPI-induced inhibition of IKCa channels was reversed by a further application of 1-ethyl-2-benzimidazolinone (10μM). THPI-induced reduction in IKCa-channel activity in these cells was primarily due to a decrease in mean open time. These results provide direct evidence that THPI is capable of suppressing the activity of IKCa channels in HL-60 cells. The antioxidant action of THPI also revealed a beneficial cytoprotective effect against mitomycin C-mediated haemolytic effect in human erythrocytes. The results of this study suggest that blockade of IKCa channels and the membrane-protecting activity of THPI would combine to have beneficial effects in lessening the severity of haemolytic crisis and reducing anaemia in sickle cell disease.
Protective effect of Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in rats
Authors: Cho Eun Ju , Yokozawa Takako , Okamoto Takuya 
Published: May 2007

Abstract
We have investigated the effect of the Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in-vivo in a rat model. The serum and hepatic triglyceride levels were remarkably elevated in 12-month-old compared with two-month-old rats. However, the administration of Kangen-karyu and Tanjin extracts significantly decreased these levels. This suggested a protective role against related pathological conditions as well as hyperlipidaemia. On the other hand, the reduction of the levels of adiponectin in serum with ageing did not show significant changes in rats given diets supplemented with Kangen-karyu and Tanjin extracts. Furthermore, the expression of transcription factors in nuclear hepatic tissue related to lipid metabolism was investigated. The decline in the expression of nuclear peroxisome proliferator-activated receptor α protein in hepatic tissue with age was ameliorated by the administration of Kangen-karyu and Tanjin supplements. On the other hand, the overexpression of sterol regulatory element-binding proteins (SREBP)-1 and SREBP-2 in old rats compared with young rats showed a tendency to decrease with Kangen-karyu and Tanjin administration. The decline of hepatic function with ageing was attenuated by Kangen-karyu and Tanjin, suggesting the beneficial role of Kangen-karyu and Tanjin on lipid metabolism through the improvement of hepatic function. This study has demonstrated that Kangen-karyu and Tanjin inhibited the accumulation of triglyceride with regulation of related protein expressions and they improved hepatic function. Evidence has been provided for the anti-ageing activity of Kangen-karyu and its crude drug Tanjin against age-related lipidosis.
Beneficial effects of the extract from Corydalis yanhusuo in rats with heart failure following myocardial infarction
Authors: Wu Limao , Ling Haiyun , Li Lianda , Jiang Lianxiu , He Minle 
Published: May 2007

Abstract
As indicated in ancient Chinese medical books, Corydalis yanhusuo has therapeutic effects on cardiovascular diseases. The analgesic effect of this plant has been fully elucidated, and I-tetrahydropalmatine has been shown to be the main active principle. The aim of this investigation was to evaluate its protective effects in a rat heart failure model. Rats were subjected to coronary artery ligation, and orally administered with ethanolic extract of Corydalis yanhusuo 50, 100, or 200 mg kg−1 daily, from the 7th day after surgery. We measured cardiac function, plasma atrial natriuretic peptide (ANP), relative heart and lung weights, infarct size and ventricular dilatation after treatment for 8 weeks. Administration with Corydalis yanhusuo led to a significant reduction in infarct size and improvement in cardiac function as demonstrated by lower left ventricular end diastolic pressure (LVEDP) and elevated ± dp/dtmax. We also found that Corydalis yanhusuo significantly reduced left ventricular (LV)/body weight ratio, lung/body weight ratio and significantly inhibited neurohormonal activation. Taken together, this study indicated that Corydalis yanhusuo exerted salutary effects on heart failure induced by myocardial infarction in rats.