bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of nelfinavir and its M8 metabolite on lymphocyte P‐glycoprotein activity during antiretroviral therapy
Authors: Donahue John P. , Dowdy David , Ratnam Krishna K. , Hulgan Todd , Price James , Unutmaz Derya , Nicotera Janet , Raffanti Steven , Becker Mark , Haas David W. 
Published: February 2003

The efflux pump P‐glycoprotein decreases drug penetration into cells and tissues. To determine whether nelfinavir or its metabolites inhibit P‐glycoprotein in lymphocytes from a healthy volunteer, whole blood cells from human immunodeficiency virus‐negative donors were incubated either in human plasma to which nelfinavir or its M8 metabolite were added ex vivo or in plasma from human immunodeficiency virus‐positive patients receiving nelfinavir. The 50% P‐glycoprotein inhibitory concentrations of purified nelfinavir and M8 were 10.9 μmol/L and 29.5 μmol/L, respectively, for CD4+ T cells and 19.3 μmol/L and >48 μmol/L, respectively, for CD8+ T cells. Significant inhibitory activity was present in plasma from 27 of 46 patients (59%) receiving nelfinavir. Plasma nelfinavir concentrations correlated with percent inhibition on CD4+ (ρ = 0.85, P < .0001) and CD8+ (ρ = 0.83, P < .0001) T cells. The M8 concentrations correlated weakly with both inhibition and nelfinavir concentrations. On the basis of our findings in lymphocytes from a healthy volunteer exposed to plasma from human immunodeficiency virus‐positive patients, we believe it is likely that CD4+ and CD8+ lymphocytes in patients receiving nelfinavir as therapy for human immunodeficiency virus may have P‐glycoprotein inhibited by plasma concentrations of nelfinavir.Clinical Pharmacology & Therapeutics (2003) 73, 78–86; doi: 10.1067/mcp.2003.11
Analgesic effects of morphine and morphine‐6‐glucuronide in a transcutaneous electrical pain model in healthy volunteers
Authors: Skarke Carsten , Darimont Jutta , Schmidt Helmut , Geisslinger Gerd , Lötsch Jörn 
Published: February 2003

ObjectiveOur objective was to quantify the extent and time course of the effects of morphine‐6‐glucuronide and morphine on pain threshold, pain tolerance, pupil diameter, and side effects.MethodsIn a double‐blind, placebo‐controlled, randomized, 3‐way crossover study, 12 healthy volunteers (6 men and 6 women) received 63 to 112 mg of morphine‐6‐glucuronide or 26 to 66 mg of morphine as an intravenous bolus, followed by an infusion of the same medication for 1.8 to 6.4 hours. Analgesia was assessed every 30 minutes for up to 16 hours by means of transcutaneous electrical stimulation (sine wave, 5 Hz; intensity, 0–9.99 mA). Pupil diameter and side effects were recorded concomitantly.ResultsAt the administered doses, morphine‐6‐glucuronide and morphine had comparable effects on pain tolerance, pupil diameter, and side effects. The delay between the time course of the plasma concentrations and the time course of the effects was longer for morphine‐6‐glucuronide than for morphine (transfer half‐life, 8.2 hours versus 2.6 hours for pain tolerance and 7.7 hours versus 2.8 hours for pupil diameter). The slope of the linear concentration versus effect relationship for pain tolerance was flatter for morphine‐6‐glucuronide than for morphine (0.05% versus 0.6% increase in pain tolerance per nanomole per liter of morphine‐6‐glucuronide and morphine at effect site, respectively). Morphine‐6‐glucuronide was less potent than morphine in producing pupil constriction (mean concentration at half‐maximum effect, 745 nmol/L versus 26.4 nmol/L for morphine‐6‐glucuronide and morphine, respectively). In carriers of the mutated G118 allele of the μ‐opioid receptor, the potency of the pupil‐constricting effects of morphine‐6‐glucuronide and morphine was significantly smaller, and carriers of the G118 allele reported less nausea and vomited less often after administration of morphine‐6‐glucuronide.ConclusionsMorphine‐6‐glucuronide clearly produced analgesic effects in healthy volunteers. However, the high amounts of systemic morphine‐6‐glucuronide needed to produce the same effects as morphine suggest that morphine‐6‐glucuronide barely contributes to the central nervous opioid effects after administration of analgesic doses of morphine.Clinical Pharmacology & Therapeutics (2003) 73, 107–121; doi: 10.1067/mcp.2003.5
Nitric Oxide and the Autonomic Regulation of Cardiac Excitability
Authors: Paterson David J. 
Published: February 2003

Contents PageIntroduction 1Cardiac sympathetic imbalance and arrhythmia 2Nitric oxide‐cGMP pathway and the cholinergic modulation of cardiac excitability 3Nitric oxide‐cGMP pathway and the sympathetic modulation of cardiac excitability 7Functional significance of nitric oxide in the autonomic regulation of cardiac excitability 9Summary 9References 10
Study of protein–protein interactions by fluorescence of tryptophan analogs: Application to immunoglobulin G binding domain of streptococcal protein G
Authors: Li Qi , Du Hai‐Ning , Hu Hong‐Yu 
Published: February 2003

AbstractThe protein–protein interaction system often contains many fluorophores that may significantly interfere with the quantitative determination of the binding abilities. To solve this perplexing problem, we biosynthetically incorporated the two tryptophan analogs, 5‐hydroxytryptophan and 7‐azatryptophan, into the immunoglobulin G (IgG) binding domain of streptococcal protein G (PGBD). The exclusive excitation and novel fluorescence changes in both the intensity and anisotropy are beneficial to reporting the details of the interactions between PGBD and the IgG fragments and enable assessment of the binding abilities. The dissociation constants are estimated to be 0.28 μM for the binding of human Fc and 8.0 μM for mouse Fc. The results clearly demonstrate that labeling of tryptophan analogs has very little effect on the binding abilities and is broadly applicable to quantitatively studying protein–protein interactions in a whole biomolecular complex. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 116–122, 2003
Detection by circular dichroism of conformational transitions in pH and thermosensitive copolymers based on N‐isopropylacrylamide and N‐methacryloyl‐L‐leucine
Authors: Lebon France , Bignotti Fabio , Penco Maurizio , Gangemi Roberto , Longhi Giovanna , Abbate Sergio 
Published: February 2003

AbstractCircular dichroism (CD) spectra in the region of 210–250 nm allow visualization of intrachain phase transition of pH‐ and thermosensitive polyelectrolytes. Indeed, in 0.001 M citrate and acetate buffers, at pH 4.0–5.5, aqueous solutions of a poly(N‐isopropylacrylamide‐co‐N‐methacryloyl‐L‐leucine) (NIPAAm‐MALEU) copolymer containing 90.9 mol% of NIPAAm residues exhibit a well‐defined sigmoidal increase in the CD signal at 220 nm with increasing temperature. This phenomenon is suggestive of a highly cooperative transition which occurs at lower temperatures compared to that observed by cloud point measurements. The change in the CD signal is less sharp at higher pH, indicating varying cooperativity with pH. For pH 6.0 and higher, no such phenomena are observed. Chirality 15:251–255, 2003. © 2003 Wiley‐Liss, Inc.
Geometrical approach to central molecular chirality: A chirality selection rule
Authors: Capozziello Salvatore , Lattanzi Alessandra 
Published: February 2003

AbstractChirality is of primary importance in many areas of chemistry and has been extensively investigated since its discovery. We introduce here a description of central chirality for tetrahedral molecules using a geometrical approach based on complex numbers. According to this representation, for a molecule having n chiral centers it is possible to define an “index of chirality χ.” Consequently, a “chirality selection rule” has been derived which allows the characterization of a molecule as achiral, enantiomer, or diastereoisomer. Chirality 15:227–230, 2003. © 2003 Wiley‐Liss, Inc.
Kinetics and thermodynamic parameters of the thermal decomposition of imipramine hydrochloride and trimipramine maleate
Authors: Abu‐Eittah Rafie H. , Kamel Laila T. 
Published: February 2003

AbstractThermal decomposition of imipramine hydrochloride and trimipramine maleate has been investigated isothermally and nonisothermally. The kinetic parameters, namely the activation energy Ea and the Arrhenius preexponential term A, were calculated. Applying the theory of activated complex to the process of decomposition one calculated ΔS≠, ΔH≠, and ΔG≠ for the reaction. The values of Ea as well as the thermodynamic functions did not vary significantly with temperature of the reaction whereas the preexponential term showed a significant dependence on the reaction temperature. Both imipramine hydrochloride and trimipramine maleate showed two main steps of decomposition. Each step proved to be a first‐order reaction. The rate constant was calculated for each step, and the results were analyzed statistically. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 166–179, 2003
Cross‐reactivity of yeast antigens in human colon and peripheral leukocytes
Authors: Oshitani1 Nobuhide , Hato Fumihiko , Suzuki Kenichi , Sawa Yoshinori , Matsumoto Takayuki , Maeda Kiyoshi , Higuchi Kazuhide , Kitagawa Seiichi , Arakawa Tetsuo 
Published: February 2003

AbstractElevation of the serum anti‐Saccharomyces cerevisiae antibody (ASCA) level has been reported in patients with Crohn's disease. This study investigated the antigenic distribution of S. cerevisiae in human colon and peripheral leukocytes. ASCA was isolated from sera from patients with Crohn's disease using immuno‐affinity chromatography and then biotinylated and assayed immunohistologically and immunocytologically to determine the distribution of antigens recognized by ASCA in human colon and peripheral leukocytes. Immunoblot analysis of yeast extract and human peripheral leukocytes was performed. Immunohistological study using biotinylated ASCA revealed the presence of yeast‐like particles in the granulation tissue of inflamed colonic mucosa. Biotinylated ASCA also stained lymphocytes and polymorphonuclear cells infiltrating inflamed intestine. Monocytes in epithelioid granulomas of colon with Crohn's disease were also stained. Polymorphonuclear leukocytes in peripheral blood were also stained with biotinylated ASCA. The antigens reactive to ASCA among heat‐extracted, non‐heat‐extracted yeast antigens, and human leukocyte extract differed. The findings of cross‐reactivity of polymorphonuclear leukocytes with S. cerevisiae antigen and the presence of S. cerevisiae antigen in Crohn's disease granulomas suggest the possibility of involvement of S. cerevisiae in the pathogenesis of Crohn's disease. Copyright © 2003 John Wiley & Sons, Ltd.
Genetic algorithm optimization of a firewater deluge system
Authors: Andrews J. D. , Bartlett L. M. 
Published: February 2003

AbstractSafety systems are designed to operate when certain conditions occur and to act to prevent their development into a hazardous situation. Failure of a safety system for a potentially hazardous industrial system or process may have catastrophic consequences, possibly injuring members of the work force or public and occasionally resulting in loss of life. The purpose of this paper is to describe a design optimization scheme using genetic algorithms applied to a firewater deluge system, which uses available resources to the best possible advantage to obtain an optimal safety system design. Copyright © 2003 John Wiley & Sons, Ltd.
Changing ideas about the periodic table of elements and students' alternative concepts of isotopes and allotropes
Authors: Schmidt Hans‐Jürgen , Baumgärtner Tim , Eybe Holger 
Published: February 2003

AbstractThe Periodic Table of Elements (PTE) is one of the organizing principles in chemistry. Originally it was a list of elements (as substances). Later, the PTE developed into a list of atoms of the elements. However, isotopes and allotropes are difficult to integrate into the PTE. Therefore, difficulties in understanding these terms can be expected. The investigation set off to study secondary school students' concepts of isotopes and allotropes and how the concepts are linked to the PTE. Three specific research questions were addressed: (a) How do secondary school students describe the relationship between fundamental particles constituting an atom? (b) How do they conceive isotopes? and (c) What are students' concepts of graphite and diamond? Multiple choice items were given to 3074 senior high school students. In addition, six interviews were conducted with senior high school students. The data analysis revealed students' alternative concepts, which distinguished between standard atoms and atoms of isotopes. Standard atoms contain neutrons and protons in equal numbers and are more stable. The atomic masses are expressed as integers. Moreover, students considered graphite and diamond as isotopes. The analysis of the results shows that students actively tried to make sense of what they had experienced. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 40: 257–277, 2003
Glutamine and glutamate—their central role in cell metabolism and function
Authors: Newsholme Philip , Procopio Joaquim , Lima Manuela Maria Ramos , Pithon‐Curi Tania Cristina , Curi Rui 
Published: February 2003

AbstractGlucose is widely accepted as the primary nutrient for maintenance and promotion of cell function. However, we propose that the 5‐carbon amino acids, glutamine and glutamate, should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine are many and include: substrate for protein synthesis, anabolic precursor for muscle growth, acid–base balance in the kidney, substrate for ureogenesis in the liver, substrate for hepatic and renal gluconeogenesis, an oxidative fuel for intestine and cells of the immune system, inter‐organ nitrogen transport, precursor for neurotransmitter synthesis, precursor for nucleotide and nucleic acid synthesis and precursor for glutathione production. Many of these functions are connected to the formation of glutamate from glutamine. We propose that the unique properties regarding concentration and routes of metabolism of these amino acids allow them to be used for a diverse array of processes related to the specialized function of each of the glutamine utilizing cells. In this review we highlight the specialized aspects of glutamine/glutamate metabolism of different glutamine‐utilizing cells and in each case relate key aspects of metabolism to cell function. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of erythropoietin and pentoxifylline on the oxidant and antioxidant systems in the experimental short bowel syndrome
Authors: Noyan Tevfik , Önem Önder , Ramazan Şekeroğlu M. , Köseoğlu Burhan , Dülger Haluk , Bayram İrfan , Sadık Yalçinkaya A. , Bakan Vedat 
Published: February 2003

AbstractIn this study, we investigated the effects of erythropoietin (Epo), and pentoxifylline (Ptx) on the oxidant and antioxidant systems in the experimental short bowel syndrome. Spraque‐Dawley rats were divided into four groups and all animals underwent 75% small bowel resection. Group E was treated with 500 IU kg− 1 Epo subcutaneously (s.c.), group P with 50 mg kg− 1 day− 1 s.c. Ptx and group E+P with 500 IU kg− 1 s.c. Epo plus 50 mg kg− 1 day− 1 s.c. Ptx for a period of 28 days. In group C, which is the control group, no drug treatment was given. At the end of 28 days the experimented rats were killed and ileum samples excised for biochemical and histopathological testing. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) levels were determined in ileum homogenates. When compared to group C, the MDA and GSH‐Px levels were significantly decreased (p < 0.05), but SOD activitiy was not changed (p > 0.05) in groups P and E+P, whereas both MDA and SOD and also GSH‐Px activities were not changed significantly in group E (p > 0.05). The average villous length, crypt depth, muscular thickness and mucosal length were measured in all groups. The average crypt depth and mucosal length were statistically higher in the group P than group C (p < 0.001, p < 0.01, respectively). In addition, the crypt depth was statistically higher in both E and E+P groups as compared to group C (p < 0.001, p < 0.01, respectively). Therefore, our study indicates that Ptx may be more effective than Epo in reducing lipid peroxidation. Moreover, we considered that Ptx may give this protective effect by inhibiting the free oxygen radicals to a greater extent than developing the antioxidant capacity. Copyright © 2002 John Wiley & Sons, Ltd.
Microcapsules made by enzymatically tailored alginate
Authors: Strand Berit L. , Mørch Yrr A. , Syvertsen Kjersti R. , Espevik Terje , Skjåk‐Bræk Gudmund 
Published: February 2003

AbstractAlginate is widely used for encapsulation of cells. Alginate is a linear block copolymer consisting of mannuronic acid (M) and guluronic acid (G). It has been shown that enzymes known as C‐5 epimerases convert M to G in the polymer chain, giving rise to novel alginates with tailored properties. One of these enzymes, AlgE4, converts M blocks into blocks of strictly alternating M and G. In this study we investigated how alginate epimerized by AlgE4 affected capsule properties such as stability and permeability. Inhomogeneous calcium‐alginate gel beads were made with original and AlgE4‐epimerized alginates of different origin. The epimerized alginates formed initially smaller alginate gels that showed increased resistance to osmotic swelling compared with the original nonmodified alginate samples. The permeability, measured as diffusion of immunoglobulin (Ig) G into Ca/Ba‐alginate gel beads, was reduced by epimerization and further reduced by addition of poly‐L‐lysine (PLL). The osmotic stability of alginate‐poly‐D‐lysine(PDL)‐alginate capsules was enhanced by the use of epimerized alginate; indeed, stable capsules with low permeability to tumor necrosis factor (TNF) could be made with low PDL exposures. Finally, alginate with an alternating structure interacted more strongly with the alginate‐PLL capsule than did alginate with a high content of M blocks or G blocks or than an alginate consisting mainly of M. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 540–550, 2003
Mixed‐ligand modification of polyamidoamine dendrimers to develop an effective scaffold for maintenance of hepatocyte spheroids
Authors: Higashiyama S. , Noda M. , Kawase M. , Yagi K. 
Published: February 2003

AbstractCompared with a monolayer culture, hepatocyte spheroids are known to maintain liver function for long periods. We found that hepatocytes formed spheroids when cultured on polyamidoamine dendrimers modified with fructose. Because galactose is a ligand for the asialoglycoprotein receptor on the hepatocyte cytoplasmic membrane, it was chosen as another ligand for modification in order to maintain adhesion of spheroids for long periods. Simultaneous modification of dendrimers with fructose and galactose had a marked effect on the time length of spheroid adhesion. Suppression of apoptosis and necrosis was observed in hepatocyte spheroids cultured on a dendrimer modified with fructose and galactose (F/G dendrimer). Moreover, the hepatocyte spheroids cultured on the F/G dendrimer had higher activities of liver‐specific functions, such as urea synthesis and albumin gene expression, than did those cultured on single‐ligand‐modified dendrimers. The expression of heat shock protein (HSP) genes was examined to evaluate the stress response of cells to scaffolds. The hepatocytes cultured on the F/G dendrimer had very low expression levels of both HSP60 and HSP70 mRNAs. Thus immobilization of mixed‐ligand‐modified dendrimers could generate a suitable surface for hepatocyte spheroid formation. These dendrimers could be a powerful tool for generating custom‐made scaffolds for cells other than hepatocytes by selecting the ligands suitable for each cell type. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 475–482, 2003
A meta‐analysis of the effectiveness of bibliotherapy for alcohol problems
Authors: Apodaca Timothy R. , Miller William R. 
Published: February 2003

AbstractThere has been increased interest in the use of brief interventions and the delivery of alcohol treatment services through nonspecialist health care settings. One possible resource for reaching untreated individuals is “bibliotherapy,” the provision of self‐help materials to motivate and guide the process of changing drinking behavior. Research on the effectiveness of self‐help materials for problem drinkers has been done for three decades. This report summarizes a meta‐analytic review of 22 studies evaluating the effectiveness of such self‐help materials. Each study was rated on 12 methodological criteria, and effect sizes of bibliotherapy were computed. The methodological quality of studies was generally high relative to other treatment‐outcome studies. Modest support was found for the efficacy of self‐help materials in decreasing at‐risk and harmful drinking. The weighted mean pre/post‐effect size for bibliotherapy was .80 with self‐referred individuals seeking help for drinking problems, and .65 for individuals identified through health screening. Between‐group comparisons of bibiotherapy with no‐intervention controls appear to have a small to medium effect, with a weighted mean effect size of .31 with self‐referred drinkers; effect size was more variable in opportunistic interventions based on health screening. Finally, between‐group comparisons of effects on drinking of bibliotherapy versus more extensive interventions yielded effect size values near zero. These findings provide support for the cost‐effective use of bibliotherapy with problem drinkers seeking such help to reduce their consumption, and to a lesser extent with drinkers who are identified through screening as at risk. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 289–304, 2003.