bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic modulation of irinotecan metabolites by sulphobromophthalein in rats
Authors: Itoh Tatsuya , Itagaki Shirou , Sasaki Kentaro , Hirano Takeshi , Takemoto Isao , Iseki Ken 
Published: June 2004

Abstract
The purpose of this study was to modulate the pharmacokinetics of irinotecan metabolites, SN-38 and SN-38-glucuronide, by possibly reducing biliary excretion, which in turn could lower irinotecan toxicity. SN-38-glucuronide is associated with severe diarrhoea that occurs after irinotecan therapy as a result of enteric injury caused by SN-38. Sulphobromophthalein is used clinically as a drug for testing liver function and is considered to be a safe drug. We investigated the effect of sulphobromophthalein on the disposition of irinotecan metabolites after CPT-11 (7-ethyl-10-[10-4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin) administration. Wistar rats were administered CPT-11 (500 μg/body) in saline as a bolus injection into the femoral vein through a catheter. The volume of drug solution injected into each animal was 1 mL. Rats were either administered CPT-11 alone or simultaneously with sulphobromophthalein (20mg/body). After administration, blood and bile samples were taken at appropriate intervals and analysed by HPLC. Co-administration of sulphobromophthalein partially inhibited the biliary excretion of SN-38-glucuronide with a concomitant increase in its area under the plasma concentration-time curve (AUC) but did not significantly alter the biliary excretion and AUC of the active metabolite SN-38. These results suggested that cotreatment of CPT-11 with sulphobromophthalein might decrease intraluminal SN-38 concentrations without altering the pharmacokinetics of SN-38.
Aqueous solubilization of furosemide by supramolecular complexation with 4-sulphonic calix[n]arenes
Authors: Yang Wenzhan , de Villiers Melgardt M 
Published: June 2004

Abstract
The solubilization of the practically water insoluble drug furosemide by guest:host inclusion complexation with 4-sulphonic calix[n]arenes has been reported. The 4-sulphonic calix[n]arenes are water-soluble phenolic cyclooligomers that form inclusion complexes with neutral molecules. The solubility of furosemide in acidic (pH &lt; 4) aqueous solutions containing increasing concentrations of the calixarenes was determined at 30°C and the concentration of furosemide in solution was determined by HPLC. Results showed that the molecular size of the 4-sulphonic calix[n]arenes and the concentration of the calix[n]arenes significantly influenced the increase in the solubility of furosemide. 4-Sulphonic calix[6]arene improved the solubility of furosemide the most (± 104%) followed by 4-sulphonic calix[8]-arene (±84–102%), while 4-sulphonic calix[4]arene increased the solubility of furosemide the least (±73–81%). The increase in furosemide solubility afforded by the calixarenes was most probably the result of the incorporation of the non-polar portions of the furosemide molecule into the non-polar cavities of the calixarenes similar to furosemide:cyclodextrin complexes. The driving force for this interaction was the reduction in the non-polar-water interfacial surface area when the furosemide (guest) molecules were inserted into the 4-sulphonic calix[n]arenes (host).
Development and application of a micro-capillary rheometer for in-vitro evaluation of parenteral injectability
Authors: Allahham A , Mainwaring D , Stewart P , Marriott J 
Published: June 2004

Abstract
A micro-capillary rheometer was developed to determine the rheology and injectability of parenteral formulations. The rheometer consisted of a micro-capillary and a glass syringe attached to an Instron that drove the syringe plunger at predetermined speeds and measured resulting forces on the plunger. The cross-head speed and the measured force were used to calculate the shear rate and the shear stress respectively, according to the Hagen-Poiseuille equation. The resulting rheograms of several Newtonian standards showed excellent linearity over a broad range of about 10 times 103 to 160 times 103 s−1 and produced accurate and reproducible viscosity determinations over the viscosity range of about 10 times 10−3 to 100 times 10−3 Pa.s. The developed methodology focussed primarily on the minimization of errors associated with the determination of the wall frictional force using both direct measurement and linear regression to determine this parameter from the data. The effect of micro-capillary diameter, syringe cross-sectional area and micro-capillary length was explored in an effort to increase the measured force so that wall frictional force errors could be minimized. The micro-capillary rheometer gave reproducible and accurate rheograms over a range of shear rates consistent with the shear rate range used in clinical practice, and showed that Newtonian and non-Newtonian rheological behaviours could be evaluated quantitatively.
Comparison of the synaptosomal uptake inhibition of serotonin by St John's wort products
Authors: Schulte-Löbbert S , Holoubek G , Müller W E , Schubert-Zsilavecz M , Wurglics M 
Published: June 2004

Abstract
Although the number of prescriptions for psychotropic drugs has decreased in recent years, prescriptions for antidepressants are still increasing (Fritze 2002). Hypericum perforatum (St John's wort) is the main psychotherapeutic herbal medicinal product used for treatment of mild-to-moderate depression. The lipophilic constituent hyperforin (2–5% of the extract) demonstrated, similarly to chemical antidepressants, a significant effect on the synaptosomal uptake inhibition of several neurotransmitters in in-vitro assays. In Germany, St John's wort products are distributed via two different markets: products that are pharmacy restricted are only allowed to be distributed in pharmacies; traditionally used products, which do not claim to have a curative character, are allowed to be sold in supermarkets. Depending on the market wherein a St John's wort product is offered, it needs to fulfill the legal requirements regarding pharmaceutical quality, safety and efficacy. Our goal was to compare the quality of St John's wort products distributed in pharmacies with that of those available from supermarkets. Therefore, the quantity of the pharmaceutical active ingredients (the phloroglucinol derivate hyperforin, the flavonoids rutin, hyperoside, isoquercitrin, quercitrin and the biflavonoid biapigenin) was determined by high-performance liquid chromatography (HPLC). The naphthodianthrones hypericines and pseudohypericines were quantified by differential pulse polarography (DPP). The efficacy of the products was investigated by measuring their activity to inhibit serotonin (5-HT) uptake in-vitro using a radio ligand uptake assay. It could be demonstrated that the products were different not only in the concentration of pharmaceutically relevant ingredients but also in showing individual IC50 values (concentration producing half-maximal inhibition) in the serotonin reuptake assay (IC50 values between 3.07 and 17.9 μg extract mL−1). The results of our study confirm the assumption that the potency of St John's wort products in inhibiting the uptake of serotonin depends on the amount of hyperforin in their dosage forms. St John's wort products having greater hyperforin content and potency on synaptosomal serotonin uptake inhibition are restricted to be sold only in pharmacies.
Acteoside protects endothelial cells against free radical-induced oxidative stress
Authors: Chiou Wen Fei , Lin Lie Chwen , Chen Chieh Fu 
Published: June 2004

Abstract
The protective effect of acteoside against membrane lipid oxidation and free radical-mediated impairment of endothelial function was investigated. Results showed that iron-mediated oxidative modification of the cell membrane in cultured bovine pulmonary endothelial cells (PAECs) was significantly attenuated by acteoside as measured by thiobarbituric acid-reactive substances (TBARS). Fenton's reagent (H2O2/Fe2+) was used to generate hydroxyl radicals (*OH) and induce oxidative stress. Acteoside not only effectively minimized the loss of cell viability induced by hydroxyl radicals in cultured endothelial cells but also countered the free radical-induced destruction of the endothelium-dependent relaxation to acetylcholine in rat aorta. Furthermore, acteoside showed a dose-dependent scavenging effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals and appeared to be the most efficient in comparison with the four reference compounds (α-tocopherol, vitamin C, probucol and resveratrol). These data suggested that acteoside protects the cell from oxidative stress and that scavenging of free radicals could be a key mechanism contributing to the cytoprotective effect of acteoside.
Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats
Authors: Warrington Jill S , Court Michael H , Greenblatt David J , von Moltke Lisa L 
Published: June 2004

Abstract
We evaluated the role of specific isoforms in the biotransformation of phenacetin and chlorzoxazone and examined the effect of age on these reactions using liver microsomes from Fischer 344 rats between 3 and 26 months of age. Using rat cDNA-expressed cytochrome P450 (CYP) enzymes, we found that phenacetin biotransformation was primarily mediated by CYP2C6 and CYP1A isoforms, while chlorzoxazone biotransformation was largely mediated by CYP2E1 and CYP1A1. Incubations with liver microsomes prepared from rats of varying ages demonstrated that both phenacetin and chlorzoxazone biotransformation declined with age. Metabolite formation rates in the old rats (25–26 months) were reduced by approximately 60–70% for these reactions. This study suggests that the activity of CYP2E and CYP1A enzymes decline with age in the rat liver. Also, the relative specificity of the index substrates phenacetin (for CYP1A2) and chlorzoxazone (for CYP2E1) in man appears not to be applicable in rats.
Influence of preparation methodology on solid-state properties of an acidic drug-cyclodextrin system
Authors: Govindarajan Ramprakash , Nagarsenker Mangal S 
Published: June 2004

Abstract
We have investigated the influence of processing variables on the solid-state of a model drug, flurbiprofen, in cyclodextrin-based systems and its effect on dissolution behaviour of the drug. The interaction between flurbiprofen and hydroxypropyl β-cyclodextrin (HP-β-CyD) was studied by NMR spectroscopy and phase solubility studies. Binary systems containing flurbiprofen and HP-β-CyD or povidone (polyvinylpyrrolidone) K30, prepared by various processes, were characterized by FTIR, DSC, XRD and dissolution studies. HP-β-CyD enhanced the solubility of flurbiprofen and increased dissolution rates from binary systems. It was found to be superior to povidone K30 in producing higher dissolution rates. The method of preparation of the binary systems and the agents used were found to have a major influence on the final solid-state of flurbiprofen. Solvents and processing conditions favouring greater interaction between flurbiprofen and the cyclodextrin during the preparation process resulted in greater extent of drug-cyclodextrin association and/or greater amorphization of the drug. Use of ammonia during the preparation of binary systems yielded solids from which very rapid drug dissolution was achieved, due to a higher extent of molecular dispersion of the drug. Processing variables therefore could significantly influence the solid-state of a drug in cyclodextrin-based formulations and thereby affect its dissolution behaviour. This could lead to significant effects on the in-vivo performance of the formulation.
Hypochlorite scavenging activity of flavonoids
Authors: Firuzi Omidreza , Mladênka Pr̂emysl , Petrucci Rita , Marrosu Giancarlo , Saso Luciano 
Published: June 2004

Abstract
Scavengers of hypochlorite, a highly reactive oxidant produced by activated phagocytes, could have potential therapeutic effects in diseases in which this oxidant plays a pathogenic role. Flavonoids are polyphenolic substances present in food plants and have been extensively studied for their antioxidant properties against various free radicals. Less is known about their reactivity with hypochlorite. In this study, the hypochlorite scavenging activity of flavonoids was investigated using a microplate assay recently developed in our laboratory. This method evaluates the ability of a substance to inhibit the formation of chloramines in human serum albumin upon oxidation by hypochlorite. Thirteen flavonoids were tested. Most of them inhibited human serum albumin oxidation at micro-molar concentrations and appeared more active than Trolox, a water-soluble equivalent of vitamin E. It was observed that the greater the number of hydroxyl substitutions, the greater the scavenging activity. The 3-hydroxy substitution seemed to be particularly important for scavenging activity, whereas the presence of a 2,3-double bond in the C ring did not. Flavonoids were found to be good hypochlorite scavengers in-vitro and further information is provided about the chemical aspects important for scavenging activity. Thus, flavonoids could have beneficial effects in diseases such as atherosclerosis in which hypochlorite plays a pathogenic role.
Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4
Authors: Mohamed Hoda E , Asker Mervat E , Ali Sousou I , Abd El Fattah Tamer M 
Published: June 2004

Abstract
Selective cardiotoxicity of doxorubicin (DOX) remains a significant and dose-limiting clinical problem. The mechanisms implicated are not yet fully defined but may involve the production of reactive oxygen species or expression of cytokines. Although patients with advanced congestive heart failure express elevated circulating levels of tumour necrosis factor-α (TNFα), little is known about the prognostic importance and regulation of TNFα in the heart in cardiac disease states. Here we tested whether the expression of TNFα, along with oxidative stress, is associated with the development of DOX-induced cardiomyopathy (DOX-CM) and whether concurrent treatment with taurine (Taur), an antioxidant, or rolipram (Rolp), a TNFα inhibitor, offer a certain protection against DOX cardiotoxic properties. DOX (cumulative dose, 12 mg kg−1) was administered to rats in six equal (intraperitoneal) injections over a period of 6 weeks. Cardiomyopathy was evident by myocardial cell damage, which was characterized by a dense indented nucleus with peripheral heterochromatin condensation and distorted mitochondria, as well as significant increase in serum levels of creatine kinase and lactate dehydrogenase. DOX also induced an increment (P &lt; 0.001) in serum TNFα and plasma nitric oxide levels. The extent of left ventricular (LV) superoxide anion, lipid peroxide measured as malondialdehyde, catalase and calcium content were markedly elevated, whereas superoxide dismutase, total and non-protein-bound thiol were dramatically decreased in DOX-treated rats. Exaggeration of DOX-CM was achieved by intraperitoneal injection of lipopolysaccharide (LPS) (1 mg kg−1) 18h before sampling and evaluated by highly significant increase in heart enzymes (P &lt; 0.001), oxidative stress biomarkers and TNFα production. Pre- and co-treatment of DOX or DOX-LPS rats with Taur (1% daily supplemented in drinking water, 10 days before and concurrent with DOX) or Rolp (3 mg kg−1, intraperitoneally, one dose before DOX administration then every 2 weeks throughout the experimental period) ameliorated the deleterious effect of both DOX and LPS on the aforementioned parameters. Meanwhile, it is noteworthy that Rolp exhibited a more preferable effect on serum TNFα level. Taur and rolipram also restored the myocardial apoptosis induced by DOX. In conclusion, a cumulative dose of DOX affected free radical and TNFα production in the heart of an experimental cardiomyopathy animal model. The current results suggest that down-regulation of these radicals and cytokines could be maintained by using the free radical scavenger Taur or, more favourably, the TNFα inhibitor Rolp.
Fumigaclavine C improves concanavalin A-induced liver injury in mice mainly via inhibiting TNF-α production and lymphocyte adhesion to extracellular matrices
Authors: Zhao Ying , Liu Junyan , Wang Jun , Wang Lei , Yin Hao , Tan Renxiang , Xu Qiang 
Published: June 2004

Abstract
Fumigaclavine C, an alkaloidal metabolite, was produced by Aspergillus fumigatus (strain No. CY018). This study examined the effect of this compound on concanavalin A (Con A)-induced liver injury in mice, a T cell-dependent model of liver damage. Con A administration resulted in severe liver injury, T lymphocyte activation and a strong increment in spleen cell adhesion, as well as in tumour necrosis factor-α (TNF-α) production. Against this liver injury, the intraperitoneal administration of fumigaclavine C dose-dependently inhibited the elevation in transaminase activity, TNF-α production in serum and the histological changes, including inflammatory infiltration, hepatocyte necrosis and degeneration and Kupffer cell hyperplasia. In addition, this compound in-vitro also inhibited the proliferation of spleen cells induced by Con A, and reduced their IL-2 and TNF-α production. Moreover, the intraperitoneal administration of fumigaclavine C inhibited the potential of spleen cells isolated from the liver-injured mice to adhere to fibronectin, laminin and type IV collagen. These results suggest that the improvement of this T cell-mediated liver injury by fumigaclavine C may be related to the inhibition of lymphocyte activation, proliferation and adhesion to extracellular matrices as well as the reduction in TNF-α production.
Carbohydrate-based therapeutics
Authors: Osborn Helen M I , Evans Philip G , Gemmell Natasha , Osborne Sadie D 
Published: June 2004

Abstract
In recent years there has been a resurgence of interest in the biological roles of carbohydrates and as a result it is now known that carbohydrates are involved in a vast array of disease processes. This review summarises progress in the development of carbohydrate-based therapeutics that involve: inhibition of carbohydrate-lectin interactions; immunisation, using monoclonal antibodies for carbohydrate antigens; inhibition of enzymes that synthesise disease-associated carbohydrates; replacement of carbohydrate-processing enzymes; targeting of drugs to specific disease cells via carbohydrate-lectin interactions; carbohydrate based anti-thrombotic agents.
A model for evaluation of laser welding efficiency and quality using an artificial neural network and fuzzy logic
Authors: Casalino G , Minutolo F Memola Capece 
Published: June 2004

For any welding process, efficiency and quality strongly depend on the energy input, which is the energy introduced per unit length of weld from a travelling heat source. The focused laser beam is one of the highest power density sources available to the welding industry today, which makes it possible to weld with very low energy input with respect to most of other welding processes. In this paper a number of stainless steel butt joints were produced by laser irradiation. The welding efficiencies were calculated as the melted volume-energy input ratio. Moreover, the weld crown and depth were measured in order to evaluate the joint quality. The collected data were interpolated and correlated to the process parameters using an artificial neural network. They were then clustered using a fuzzy C-means algorithm. During the training stage of the neural network algorithm, the design of experiment (DOE) technique was used for the selection of the optimized network parameters. In practice, using some artificial intelligence, a model was built to choose the most suitable laser welding process for producing high efficiency and good quality, and is now available for supporting design and research.
Fine-tuning of the rolling mill using an Internet-based on-line application-processing interface
Authors: Cser L , Naude J 
Published: June 2004

In order to meet the challenge of steady growing pressure to improve product quality, rolling mills employ extensive automation and sophisticated on-line data sampling techniques. However, the steel sheet quality is influenced by the entire ‘life history’ of the rolled strip.Application of the self-organizing maps helps to discover hidden dependencies influencing the quality parameters, such as flatness, profile, wedge, thickness and width deviations and surface quality, as well as mechanical and magnetic properties. A dataset collected from the measured parameters in a strip location corresponds to a proper process state, described by a point in the state space. Time series of points corresponding to each sampled data set show how the system ‘moves’ in the state space and how the predicted product quality is changing within the strip.
Accidents, injuries and safety priorities for light goods vehicles in Great Britain
Authors: Lenard J , Frampton R , Kirk A , Morris A , Newton R , Thomas P , Fay P A 
Published: June 2004

This study presents data on light goods vehicle (LGV) crashes. The data are derived from two main sources. The first source involves mass analysis of crashes involving LGVs recorded in the national British STATS19 accident database for 1994 to 2000. The second source involves analysis from an in-depth study of LGV accidents in Britain since the late 1980s. In total, in-depth data on almost 500 LGV crashes are considered. Three main issues are apparent. Firstly, there is an issue of crash compatibility between LGVs and passenger cars. The second issue involves restraint use among LGV occupants, since the in-depth data reveal that use is low compared with car occupants. The third issue is the implications of introducing a regulatory compliance crash test for LGVs.
NbCl5-catalyzed Rapid and Efficient Synthesis of 3,4-Dihydropyrimidinones Under Ambient Conditions
Authors: Yadav J S , Reddy B V S , Naidu Jaishri J , Sadashiv K 
Published: June 2004

Abstract
Three-component condensation of an aldehyde, 1,3-dicarbonyl compound and urea or thiourea proceeds smoothly at room temperature in the presence of 5 mol % of NbCl5 under extremely mild conditions to afford the corresponding 3,4-dihydropyrimidines in high to quantitative yields. This method is very useful for the synthesis of a wide range of dipyrimidinones at room temperature from aromatic, heterocyclic, and aliphatic aldehydes.
Characterization of the Chiral Paramagnetic Multispin System Built on a Cyclotriphosphazene Scaffold
Authors: Shimono Satoshi , Tamura Rui , Ikuma Naohiko , Takahashi Hiroki , Sakai Naoko , Yamauchi Jun 
Published: June 2004

Abstract
Chiral nitroxide–cyclotriphosphazene hybrid compounds such as 2,2-dinitroxide (1a), 2,2,4,4-tetranitroxide (2a), and 2,2,4,4,6,6-hexanitroxide (3a) have been prepared to examine the potentiality for the use of the cyclotriphosphazene framework as a molecular scaffold for elaborating robust, chiral paramagnetic multispin systems. EPR spectroscopic studies of these compounds in solution and in frozen solvent matrixes indicate the existence of appreciable intramolecular electron-exchange interactions between two or three neighboring radical moieties disposed on the same side of the cyclotriphosphazene ring. Their bulk paramagnetic properties have also been characterized by magnetic susceptibility measurements.
Lithium Acetate-catalyzed Mannich-type Reaction between Trimethylsilyl Enolates and Aldimines in a Water-containing DMF
Authors: Takahashi Eiki , Fujisawa Hidehiko , Mukaiyama Teruaki 
Published: June 2004

Abstract
Lithium acetate-catalyzed Mannich-type reaction between trimethylsilyl enolates and aldimines proceeded smoothly in dry or even in a water-containing DMF to afford the corresponding β-amino carbonyl compounds in good to high yields under mild conditions.