bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensity of18Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes Between Indolent and Aggressive Non-Hodgkin’s Lymphoma
Authors: Schöder Heiko , Noy Ariela , Gönen Mithat , Weng Lijun , Green David , Erdi Yusuf E. , Larson Steven M. , Yeung Henry W.D. 
Published: April 2005

Purpose18Fluorodeoxyglucose positron emission tomography (FDG PET) is widely used for the staging of lymphoma. We investigated whether the intensity of tumor FDG uptake could differentiate between indolent and aggressive disease.Materials and MethodsPET studies of 97 patients with non-Hodgkin's lymphoma who were untreated or had relapsed and/or persistent disease and had not received treatment within the last 6 months were analyzed, and the highest standardized uptake value (SUV) per study was recorded. Correlations were made with histopathology.ResultsFDG uptake was lower in indolent than in aggressive lymphoma for patients with new (SUV, 7.0 ± 3.1 v 19.6 ± 9.3; P < .01) and relapsed (SUV, 6.3 ± 2.7 v 18.1 ± 10.9; P = .04) disease. Despite overlap between indolent and aggressive disease in the low SUV range (indolent, 2.3 to 13.0; aggressive, 3.2 to 43.0), all cases of indolent lymphoma had an SUV ≤ 13. A receiver operating characteristic (ROC) analysis demonstrated that the SUV distinguished reasonably well between aggressive and indolent disease (area under ROC curve, 84.7%), and an SUV > 10 excluded indolent lymphoma with a specificity of 81%. With a higher cutoff for the SUV, the specificity would have been higher.ConclusionFDG uptake is lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. This information may be helpful if there is discordance between biopsy and clinical behavior.
Effect of the anticancer drug oracin on mouse liver topoisomerases I and II
Authors: Stuchlík Stanislav , Turn̂a Ján , Miko Milan 
Published: April 2005

Abstract
The inhibitory effect of oracin on the activities of topoisomerases I and II isolated from the nuclei of mice liver tissue was studied. This drug showed a 100% inhibitory effect at 5 μm and 50% inhibition at 1 μm on topoisomerase II activity, while the activity of topoisomerase I at these concentrations was not inhibited.
Multidrug resistance modulator interactions with neutral and anionic liposomes: membrane binding affinity and membrane perturbing activity
Authors: Castaing Madeleine , Loiseau Alain , Mulliert Guillermo 
Published: April 2005

Abstract
A variety of cationic lipophilic compounds (modulators) have been found to reverse the multidrug resistance of cancer cells. In order to determine the membrane perturbing efficacy and the binding affinity of such drugs in neutral and anionic liposomes, the leakage of Sulfan blue induced by five modulators bearing different electric charges was quantified using liposomes with and without phosphatidic acid (xEPA = 0 and 0.1), at four lipid concentrations. The binding isotherms were drawn up using the indirect method based on the dependency of the leakage rate on the modulator and the lipid concentrations. Upon inclusion of negatively charged lipids in the liposomes: (i) the binding of cationic drugs was favoured, except in a case where modulator aggregation occurred in the lipid phase; (ii) the drugs with a net electric charge greater than 1.1 displayed a greater enhancement in their potency to produce membrane perturbation; and (iii) the EPA effect on membrane permeation was due mainly to that on membrane perturbation (≥50%) and, to a lesser extent, to that on the binding affinity (≤50%). The present study provides evidence that drug-membrane interactions are the result of a complex interplay between the structural and electrical characteristics of the drugs and those of the membranes.
Protective effect of aqueous garlic extract against naphthalene-induced oxidative stress in mice
Authors: Omurtag Gülden Z , Güranlioǧlu F Deniz , Şehirli Özer , Arbak Serap , Uslu Bahar , Gedik Nursal , Şener Göksel 
Published: April 2005

Abstract
The aim of this study was to investigate the possible protective effects of aqueous garlic extract (AGE) against naphthalene-induced oxidative changes in liver, kidney, lung and brain of mice. Balb/c mice (25–30 g) of either sex were divided into five groups each comprising 10 animals. Mice received for 30 days: 0.9% NaCl, i.p. (control); corn oil, i.p; AGE in a dose of 125 mg kg−1, i.p.; naphthalene in a dose of 100 mg kg−1, i.p. (dissolved in corn oil); and AGE (in a dose of 125 mg kg−1, i.p.) plus naphthalene (in a dose of 100 mg kg−1, i.p.). After decapitation, liver, kidney, lung and brain tissues were excised. Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase activity (MPO) were determined in the tissues, while oxidant-induced tissue fibrosis was determined by collagen content. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels and blood urea nitrogen and creatinine concentrations were measured for the evaluation of hepatic and renal function, respectively. MDA and GSH levels were also assayed in serum samples. In the naphthalene-treated group, GSH levels decreased significantly, while MDA levels, MPO activity and collagen content increased in the tissues (P&lt; 0.01–0.001), suggesting oxidative organ damage, which was also verified histologically. In the AGE-treated naphthalene group, all of these oxidant responses were reversed significantly (P&lt; 0.05–0.01). Hepatic and renal function test parameters, which increased significantly (P&lt; 0.001) following naphthalene administration, decreased (P&lt; 0.05–0.001) after AGE treatment. The results demonstrate the role of oxidative mechanisms in naphthalene-induced tissue damage. The antioxidant properties of AGE ameliorated oxidative organ injury due to naphthalene toxicity.
The use of hypromellose in oral drug delivery
Authors: Li Chi L , Martini Luigi G , Ford James L , Roberts Matthew 
Published: April 2005

Abstract
Hypromellose, formerly known as hydroxypropylmethylcellulose (HPMC), is by far the most commonly employed cellulose ether used in the fabrication of hydrophilic matrices. Hypromellose provides the release of a drug in a controlled manner, effectively increasing the duration of release of a drug to prolong its therapeutic effect. This review provides a current insight into hypromellose and its applicability to hydrophilic matrices in order to highlight the basic parameters that affect its performance. Topics covered include the chemical, thermal and mechanical properties of hypromellose, hydration of the polymer matrices, the mechanism of drug release and the influence of tablet geometry on drug-release rate. The inclusion of drug-release modifiers within hypromellose matrices, the effects of dissolution media and the influence of both the external environment and microenvironment pH within the gel matrix on the properties of the polymer are also discussed.
Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7])
Authors: Kobayashi Yasuna , Ohshiro Naomi , Sakai Ryoko , Ohbayashi Masayuki , Kohyama Noriko , Yamamoto Toshinori 
Published: April 2005

Abstract
Human organic anion transporter 2 (hOat2 [SLC22A7]) is highly expressed in the human liver. Although localization, gene expression, substrate specificity and transport mechanisms of other human Oat isoforms such as human Oat1 (hOat1), human Oat3 (hOat3) and human Oat4 (hOat4) have been elucidated, information concerning human Oat2 (hOat2) is less defined. The objective of this study was to provide further information on the transport mechanism and substrate specificity of hOat2. When expressed in Xenopus laevis oocytes, the transport of organic compounds mediated by hOat2 was not affected by the replacement of extracellular sodium with lithium, choline and mannitol. The uptake of estrone sulfate (ES) in hOat2-expressing oocytes was significantly trans-stimulated by preloading the oocytes with fumarate and succinate, but not glutarate. Moreover, we observed that hOat2 mediates the transport of bumetanide, ES, glutarate, dehydroepiandrosterone sulfate, allopurinol, prostaglandin E2, 5-fluorouracil, paclitaxel and L-ascorbic acid. These compounds are identified for the first time as hOat2 substrates. A wide range of structurally unrelated organic compounds inhibited the hOat2-mediated uptake of tetracycline, except for sulfobromophthalein. All of these findings indicate that hOat2 is a sodium-independent multi-specific organic anion/dimethyldicarboxylate exchanger. Our present findings thus provide further insights into the role of hOat2 in hepatic drug transport.
Improvement of diabetic states in streptozotocin-induced type 1 diabetic rats by vanadyl sulfate in enteric-coated capsules
Authors: Fugono Jun , Yasui Hiroyuki , Sakurai Hiromu 
Published: April 2005

Abstract
Chronic oral administration of vanadyl sulfate has recently been shown to improve the state of type 2 diabetic subjects. Mild gastrointestinal symptoms and side effects, however, have been observed in some subjects. To find safer and more effective dosages, we have developed an enteric-coated capsule containing solid vanadyl sulfate (ECC/VS), which enhances the bioavailability of vanadyl sulfate to almost double that of vanadyl sulfate solution. ECC/VS was chronically administered to treat streptozotocin-induced diabetic rats (STZ-rats), an animal model of type 1 diabetes mellitus, and an equivalent blood-glucose-lowering effect was observed at half the doses of vanadyl sulfate alone. In addition, we observed almost the same total vanadium levels in the serum after chronic administration of ECC/VS as those of vanadyl sulfate alone, suggesting that plasma vanadium levels correlate with the hypoglycaemic activity of vanadyl sulfate. These results indicate that oral ECC/VS improves the diabetic state by enhancing the uptake of vanadium in STZ-rats. These findings will be useful in designing clinical trials of vanadyl sulfate for diabetic subjects.
Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs and Valeriana edulis hydroalcoholic extract in mice*
Authors: Ugalde Martha , Reza Victoria , González-Trujano Ma Eva , Avula Bharathi , Khan Ikhlas A , Navarrete Andrés 
Published: April 2005

Abstract
It has been declared frequently that valerian may potentiate the effect of other central nervous system (CNS) depressant drugs, however there has been a lack of experimental data. We have evaluated the profile of the interactions between the ethanol extract of Valeriana edulis spp procera and six CNS depressant drugs using an exploratory model to test the sedative effect in mice. All the compounds tested showed a dose-dependent sedative effect with the following ED50 values: valerian 181.62, diazepam 1.21, ethanol 1938, pentobarbital 11.86, buspirone 1.04, haloperidol 0.41 and diphenhydramine 17.06 mg kg−1. An isobolographic analysis was used to evaluate the sedative interaction of the intraperitoneal co-administration of 1:1 fixed-ratio combination of equi-effective doses of valerian extract with each CNS depressant drug. The ED50 theoretical (Zadd) and experimental (Zexp) for each combination were: valerian + diazepam, Zadd = 91.41 mg kg−1, Zexp = 81.64 mg kg−1; valerian + ethanol, Zadd = 1060.22 mg kg−1, Zexp = 687.89 mg kg−1; valerian + pentobarbital, Zadd = 96.74 mg kg−1, Zexp = 151.83 mg kg−1; valerian + buspirone, Zadd = 91.33 mg kg−1, Zexp = 112.73 mg kg−1; valerian + haloperidol, Zadd = 91.01 mg kg−1, Zexp = 91.52 mg kg−1; valerian + diphenhydramine, Zadd = 99.34 mg kg−1, Zexp = 123.52 mg kg−1. Neither synergistic nor attenuate effects were found in any of the combinations evaluated. We concluded that the valerian extract did not potentiate the sedative effect of commonly prescribed CNS depressant drugs as was expected. The additive effect found through the isobolographic analysis suggested that the sedative effect of V. edulis resulted from the activation of common mechanisms of haloperidol, diazepam, buspirone, pentobarbital, diphenhydramine and ethanol.
Modulation of intestinal transport of 2,4-dinitrophenyl-S-glutathione, a multidrug resistance-associated protein 2 substrate, by bilirubin treatment in rats
Authors: Yokooji Tomoharu , Murakami Teruo , Ogawa Kumiko , Yumoto Ryoko , Nagai Junya , Takano Mikihisa 
Published: April 2005

Abstract
The effect of bilirubin treatment on intestinal transport of 2,4-dinitrophenyl-S-glutathione (DNP-SG), a substrate of multidrug resistance-associated protein 2 (MRP2), after application of 1-chloro-2, 4-dinitrobenzene (CDNB), a precursor of DNP-SG, was examined in rat intestine by the in-vitro everted sac, in-situ re-circulating perfusion, and in-situ loop methods. CDNB was taken up rapidly by jejunum and ileum, and the consequent intestinal efflux of DNP-SG, a glutathione conjugated metabolite of CDNB, was significantly higher in jejunum than in ileum in the in-situ and in-vitro studies. Co-administration of bilirubin (100 μM), as well as probenecid (1 mM) or ciclosporin (100 μM), with CDNB decreased the DNP-SG efflux in jejunum significantly, but not in ileum. The suppression of DNP-SG efflux in jejunum was also observed after intravenous administration of bilirubin (85.5 μmol kg−1), in which plasma bilirubin glucuronide levels were approximately 100 μM. In the in-vitro metabolism study, bilirubin exerted no significant effect on CDNB metabolism in the intestinal S9 fraction (supernatant of 9000 g). These results suggested that the diseased states accompanied with hyperbilirubinaemia might have increased the intestinal absorption, or oral bioavailability, of MRP2 substrates by suppressing MRP2 function at the proximal intestinal region.
Pre-clinical pharmacokinetics of the cyclooxygenase-inhibiting nitric oxide donor (CINOD) AZD3582
Authors: Fagerholm U , Breuer O , Swedmark S , Hoogstraate J 
Published: April 2005

Abstract
The pre-clinical pharmacokinetics of AZD3582 (4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate) and its primary metabolites (naproxen and nitrate) were evaluated. AZD3582 had intermediate and passive intestinal permeability (40 times lower than for naproxen), high systemic plasma clearance (CL), substantial gastrointestinal hydrolysis, intermediate volume of distribution (Vss; ≥3.4 L kg−1) and half-life (t1/2; 7 h), negligible plasma protein binding (∼0.1%), low/intermediate oral uptake (≥13% as intact substance) and low and varying oral bioavailability (mean 1.4% in minipigs and 3.9% in dogs). Following administration of therapeutically relevant oral doses, plasma concentrations of AZD3582 were very low (≤ 13 nM in minipigs and ≤442 nM in dogs; rat data not available) and varying, and accumulation was not apparent. The pharmacokinetics of AZD3582 did not show apparent dose-, time- or gender-related dependency. In blood and intestine, AZD3582 was hydrolysed to naproxen, nitrate and other metabolites. The rate of this conversion was higher in rats than in non-rodents, including man. Despite near-complete to complete uptake of the oral dose, AZD3582 administration resulted in a lower bioavailability (F) of total naproxen than naproxen administration: 55% and 85% relative bioavailability (Frel) in rats and minipigs, respectively. An increased distribution to metabolizing tissues of naproxen (as AZD3582), and thereby enhanced naproxen CL, is believed to be responsible. Following dosing of AZD3582 or naproxen, the t1/2 of naproxen was 5, 9–10 and &gt;40 h in rats, minipigs and dogs, respectively. The Vss and CL for naproxen were small. Plasma protein binding was extensive, and saturation was observed within the therapeutic dose and concentration range. Intake of food prolonged the systemic absorption of naproxen in the minipig. The pharmacokinetics of naproxen did not show apparent time- or gender-related dependency. Following oral dosing of [3H]-, [14C]- and [15N]-AZD3582, most [14C]- and [3H]-activity was excreted in urine and expired air, respectively. Seventeen per cent of [15N] was recovered in minipig urine as [15N]-nitrate. About 30% of [3H]-activity (naproxen and/or naproxen-related metabolites) was excreted in bile and re-absorbed. Concentrations of [14C]-activity (nitrooxy-butyl group and/or its metabolites) in milk were higher than in plasma and [3H]-activity in milk. [3H]- and [14C]-excretion data indicated that intact AZD3582 was not excreted in urine, bile or milk to a significant extent. There was no apparent consistency between tissue distribution of [14C]- and [3H]-activity in the rat, which suggests rapid and extensive metabolism of extravascularly distributed AZD3582. A substantial increase of plasma nitrate levels was found after single and repeated oral doses of AZD3582 in the minipig. No inhibition or induction of CYP450 was found.
A site-specific controlled-release system for metformin
Authors: Di Colo Giacomo , Zambito Ylenia , Baggiani Andrea , Carelli Vera , Serafini Maria Francesca 
Published: April 2005

Abstract
Oral absorption of the antihyperglycaemic agent metformin hydrochloride (MF-HCl) is confined to the upper part of the intestine, therefore rational controlled-release formulations of this drug should ensure a complete release during transit from stomach to jejunum. The aim of this study was the preparation of a system able to sustain release of high MF-HCl doses in compliance with the above requirement. Matrices (6 mm diameter; 50 mg weight) comprising varying drug-Precirol ATO 5 ratios were prepared by compression. The matrix containing 70% drug was coated on one face with Eudragit L100–55. Drug release to simulated gastric (SGF), jejunal (SJF) and ileal (SIF) fluids in sequence was studied using a modified USP rotating basket method. Release depended on drug load whereas it was independent of dissolution medium pH and hydrodynamics. Release kinetics were of √t type and were determined by drug diffusion in aqueous pores created in the matrix by drug dissolution. An equation correlating rate-determining factors was developed, whereby the release pattern could be optimized. The half-coated matrix started release in SGF and completed it in SJF. The half-coated matrix, synchronizing drug release and matrix transit across the small intestine, may improve drug bioavailability and reduce side effects.
Influence of the Ginkgo extract EGb 761 on rat liver cytochrome P450 and steroid metabolism and excretion in rats and man
Authors: Chatterjee Shyam S , Doelman Cees J A , Nöldner Michael , Biber Anton , Koch Egon 
Published: April 2005

Abstract
Extracts from leaves of Ginkgo biloba L. are among the most used herbal medicinal products worldwide. Based on in-vitro tests and studies in rats, concern has been expressed that intake of Ginkgo extracts may affect hepatic metabolism of xenobiotics and cause drug interactions, although no evidence for modulation of cytochrome P450 (CYP450) enzyme activity was obtained in human trials. Because of these contradictory findings, we investigated the effects of the standardised extract EGb 761 on hepatic CYP450 in rats. EGb 761 (100 mg kg−1 daily, p.o., for 4 days) strongly increased liver CYP450 content and altered the ex-vivo biotransformation of androstendione, as well as metabolism of endogenous steroids. However, in human subjects no effect on the urinary steroid profile was observed after intake of EGb 761 for 28 days (240 mg daily). These results indicate that the effects of EGb 761 on drug metabolising enzymes are specific for rats and may not be extrapolated to man.
Nelumbinis Semen reverses a decrease in hippocampal 5-HT release induced by chronic mild stress in rats
Authors: Kang Moonkyu , Pyun Kwang-Ho , Jang Choon-Gon , Kim Hyuntaek , Bae Hyunsu , Shim Insop 
Published: April 2005

Abstract
Depression is associated with a dysfunctional serotonin system. Recently, several lines of evidence have suggested that a very important evoking factor in depression may be a serotonin deficit in the hippocampus. This study assessed the antidepression effects of Nelumbinis Semen (NS) through increasing serotonin concentrations under normal conditions and reversing a decrease in serotonin concentrations in rat hippocampus with depression-like symptoms induced by chronic mild stress (CMS). Using an in-vivo microdialysis technique, the serotonin-enhancing effect of NS on rat hippocampus was investigated and its effects compared with those of two well-known antidepressants, Hypericum perforatum (St John's wort) and fluoxetine (Prozac). Rats were divided into five groups: saline-treated normal, without CMS; saline-treated stress control; NS-, St John's wort- and fluoxetine-treated rats under CMS for 8 weeks or no stress treatment. NS and fluoxetine significantly increased serotonin in normal conditions and reversed a CMS-induced decrease in serotonin release in the hippocampus (P&lt; 0.05 compared with normal group or control group under CMS). These results suggest that NS increases the serotonin levels normally decreased in depression, resulting in an enhancement of central serotonergic transmission and possible therapeutic action in depression. It is suggested that NS may present an antidepressant effect through enhancement of serotonin.
Sensoreigenschaften von Aktoren (Characteristics of Self-Sensing Actuator Systems)
Authors: Pawelczak Dieter R. , Tränkler Hans-Rolf 
Published: April 2005

Abstract
Die in Aktorsystemen implizit enthaltenen Messeffekte können mit geeigneten Methoden der Signalverarbeitung ausgewertet werden und ermöglichen es, zusätzliche Sensoren für Position, Geschwindigkeit oder Kraft einzusparen. Nutzbare Messeffekte verschiedener elektro-mechanischer Aktortypen werden vorgestellt. Der Einfluss der statischen und dynamischen Kopplung zwischen Aktor- und Sensorsignal auf typische Sensoreigenschaften (Empfindlichkeit, Linearität, Temperaturverhalten) wird am Beispiel eines elektromagnetischen Antriebs diskutiert.
I
nter
P
ro
Authors: Mulder Nicola J. 
Published: April 2005

Abstract
InterPro is an integrated resource for protein families, domains, and active sites. The resource provides an invaluable means for automatic classification of protein sequences into families or domains with a view to providing functional annotation for the proteins. It constitutes an amalgamation of the major protein signature databases: PROSITE, PRINTS, Pfam, ProDom, SMART, TIGRFAMs, PIR SuperFamily, and SUPERFAMILY into a unified database where similarities and differences between the signatures from each of these databases are rationalized for ease of use. All signatures representing the same family or domain are collated into unique InterPro entries, with annotation and a list of the proteins in UniProt that these signatures match. New sequences not available in UniProt can be run through all signatures in InterPro using the InterProScan software. InterPro is useful for large‐scale classification of whole genomes, as well as for functional annotation of individual protein sequences.
Infrared Spectroscopy
Authors: Stuart Barbara 
Published: April 2005

AbstractInfrared ir spectroscopy is one of the most important analytical techniques available to scientists. One of the great advantages of ir spectroscopy is that virtually any sample may be studied in any state. Liquids, solutions, pastes, powders, films, fibers, gases, and surfaces all can be examined with a judicious choice of sampling technique. The basic theory of ir spectroscopy is described, including the vibrations of molecules that are crucial to the interpretation of ir spectra. Fourier transform (ft) spectrometers are described as these are the most widely used instruments. The sampling procedure used in ir spectroscopy depends very much on the type of sample to be examined. The various sampling techniques commonly available are outlined. Spectrum interpretation is also discussed outlining how information may be gained from an ir spectrum. Infrared spectroscopy is now used in a wide variety of scientific fields and some of the applications of the technique are summarized: organic and inorganic molecules, polymers, biological and industrial applications are reviewed.