bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Streptozotocin-induced Diabetes and Aldose Reductase Inhibition with Sorbinil, on Left and Right Atrial Function in the Rat
Authors: Sellers Donna J , Chess-Williams Russell 
Published: October 2002

Abstract
Diabetes mellitus is frequently associated with the complications of cardiovascular disease. Activation of the aldose reductase (or polyol) pathway has long been implicated as an underlying factor for the development of many diabetic complications and indeed, treatment with aldose reductase inhibitors has been shown to prevent or reverse many of these diabetic complications. This study examines the effects of 14-day streptozotocin-induced diabetes on α1 and β-adrenoceptor-mediated responses in rat isolated left and right atria. The effects of treatment with the aldose reductase inhibitor (ARI) sorbinil were also studied. A positive inotropic response was observed to both isoprenaline and phenylephrine in left atria. Diabetes of 14 days duration resulted in a supersensitivity of these tissues to the β-adrenoceptor agonist in comparison with controls, while responses to the α1-adrenoceptor agonist were unaltered. Spontaneously beating right atria from diabetic rats was found to have a depressed resting rate compared with control tissues, although positive chronotropic β-adrenoceptor-mediated responses were not affected by diabetes. Phenylephrine produced α1-adrenoceptor-mediated chronotropic responses in right atrial tissues, and these were found to be enhanced in rats with diabetes. Treatment of diabetic rats with the ARI sorbinil was successful in preventing only one of the observed diabetes-induced changes in atrial function, namely the supersensitivity of left atria to isoprenaline. Sorbinil treatment did, however, alter responses of control left and right atria in a manner similar to diabetes.
In conclusion, streptozotocin-induced diabetes of 14 days duration was found to cause a number of alterations in the functioning of both left and right atria. ARI treatment with sorbinil failed to prevent all but one of these changes, and in addition altered responses of atria from control rats, having a similar effect to that produced by diabetes. These data suggest that sorbinil may have effects in addition to, and independent of, aldose reductase inhibition in the cardiovascular system.
Liquid Chromatography-Atmospheric Pressure Chemical Ionization Mass Spectrometry as a Tool for the Characterization of Anthraquinone Derivatives from Chinese Herbal Medicine
Authors: Li Wenkui , Chan Chi-Leung , Lueng Hei-Wun 
Published: October 2002

Abstract
We have examined the anthraquinone derivatives of a Chinese herb medicine ‘Rhubarb’ by using HPLC/MS/MS, equipped with an atmospheric pressure chemical ionization source.
The simultaneous determination of five ingredients in the sample extracts by HPLC/MS/MS was demonstrated. Product ion spectra of these components in the extracts were obtained and matched against known standards. Concentrations of these active ingredients were estimated by multiple reaction monitoring in the negative ion mode using a single HPLC run.
Aerosol Delivery of Amphotericin B Desoxycholate (Fungizone) and Liposomal Amphotericin B (AmBisome): Aerosol Characteristics and In-vivo Amphotericin B Deposition in Rats
Authors: Ruijgrok E J , Vulto A G , Van Etten E W M 
Published: October 2002

Abstract
In the treatment or prophylaxis of invasive pulmonary aspergillosis, it may be attractive to administer the antifungal agent amphotericin directly to the pulmonary route via aerosol inhalation. In this study, we describe the aerosol characteristics of aerosolized non-liposomal amphotericin B (Fungizone) and liposomal amphotericin B (AmBisome), and the in-vivo aerosol deposition.
Aerosols were generated with a Collison nebulizer. Aerosol amphotericin concentrations and mass median diameters were measured. In-vivo pulmonary deposition was evaluated by measuring amphotericin concentrations in lungs of treated rats. Whole body aerosol deposition was determined by measuring radioactivity in tissues of rats after treatment with radiolabelled liposomes. For Fungizone and AmBisome, aerosol amphotericin concentrations were 24.5 ± 4.9 and 23.8 ± 3.0 μg L−1, respectively. The values for the median mass diameter were 1.38 and 2.26 μm for Fungizone and 2.43 and 1.97 μm for AmBisome. Amphotericin concentrations in lungs after 60-min nebulization of Fungizone or AmBisome were 24.2 ± 6.4 and 21.7 ± 2.6 μg g−1, respectively. After nebulization of radiolabelled liposomes, no radioactivity was retrieved from tissues other than the lungs or the gastrointestinal tract. Nebulization of either Fungizone or AmBisome leads to respirable aerosols and results in a substantial lung tissue concentration of amphotericin and low systemic exposure of amphotericin B. Aerosol administration of either Fungizone or AmBisome may be an attractive approach to prevent or treat pulmonary aspergillosis.
Anthraquinone-Oligodeoxynucleotide Conjugates as Inhibitors of Gene Transcription
Authors: Gibson V , Anderson R J , Hartley J A , McAdam S R , Cairns D 
Published: October 2002

Abstract
Several anthraquinone-oligodeoxynucleotide conjugates have been synthesized and their inhibition of transcription of the bla gene in E. coli has been determined.
All conjugates at 10 μm inhibited transcription and three conjugates inhibited mRNA production by 40 to 50% for periods of up to 60 min.
The Use of Atomic Charges and Orbital Energies as Hydrogen-bonding-donor Parameters for QSAR Studies: Comparison of MNDO, AM1 and PM3 Methods
Authors: Ghafourian Taravat , Dearden John C 
Published: October 2002

Abstract
Hydrogen-bonding, important in drug-receptor interactions, also determines the solubility and partitioning of drugs between phases. It is, therefore, important to incorporate the effects of hydrogen-bonding in studies of quantitative structure-activity relationships (QSAR).
In this study the atomic charge on the most positively charged hydrogen atom in a molecule and the energy of the lowest unoccupied molecular orbital (LUMO) have been used as a measure of hydrogen-bond-donor capacity. For several hydrogen-bonding acids the Mulliken atomic charges and the energy of the LUMO produced by use of three semi-empirical methods, AM1, PM3 and MNDO, and MNDO electrostatic-potential-derived atomic charges, have been compared in correlations with solvatochromic hydrogen-bonding acidity (σα2H).
Atomic charges and LUMO energies, particularly those calculated by use of the AM1 and MNDO methods, were found to correlate well with σα2H. They were also found to be good models of hydrogen-bonding in QSAR correlations.
Inert Gas Sparge Leads to Alternate Reaction Pathway
Authors: Franchini Miriam K , Carstensen Jens T 
Published: October 2002

Abstract
The effect of sparging with an inert gas (argon) was evaluated during the investigation of the solution kinetics of an oxidation-prone amphiphilic drug containing a sulphide moiety.
Samples stored with an air headspace in pH 7 and 8 phosphate buffers at elevated temperatures and in the absence of light degraded to two main products, a sulphoxide and a cinnamic acid analogue. Initially, this appeared to be a sequential mechanism which could be blocked by removing oxygen. Instead, argon-sparge forced the direct degradation to the cinnamate, which was evidenced by the formation of a strong odour of sulphide. In addition, argon-sparged samples remained colourless, while those sparged with oxygen or stored with an air headspace turned yellow and had negligible odour. The half-lives for samples stored in pH 8 buffers at 93°C at an initial drug concentration of 25 mg mL−1 were 128 days (argon sparged), 86 days (air headspace), and 65 days (oxygen sparged).
The results indicated that for the drug under study, sparging with an inert gas affected the mechanism as well as the rate of the reaction at elevated temperatures.
Distribution of α1L-Adrenoceptors in Canine Prostate: Characterization by Quantitative Autoradiography
Authors: Suzuki Yasunori , Moriyama Nobuo , Okaya Yuki , Kanada Atsunori , Nishimatsu Hiroaki , Kawabe Kazuki , Aisaka Kazuo 
Published: October 2002

Abstract
Our aim was to determine the distribution of α1L-adrenoceptors in canine prostate by an autoradiographic technique using [3H]JTH-601 (an α1L-adrenoceptor antagonist) and [3H]JTH-601-G1 (an active metabolite of JTH-601).
Prostates were removed from three male beagle dogs. Several slices of the specimens were incubated with 5 nm of [3H]JTH-601, [3H]JTH-601-G1 and [3H]tamsulosin (an α1A-adrenoceptor antagonist). For macroscopic autoradiography, visualization was performed using an imaging plate and image-analyser. To examine microscopic localization of binding sites, preparations were exposed, developed and fixed.
Specific binding of [3H]JTH-601 and [3H]JTH-601-G1 was observed diffusely throughout the entire interstitium on macroscopic autoradiography. Specific binding of [3H]tamsulosin was also recognized although the binding was weaker than that of [3H]JTH-601. On microscopic autoradiograms, the grains of each ligand were mainly distributed on smooth muscle.
These results indicate morphologically that specific binding sites of JTH-601 and JTH-601-G1 exist in canine prostate, suggesting the distribution of α1L-adrenoceptors in this tissue, in addition to α1A-adrenoceptors.
Anti-hypercholesterolaemia, Antioxidant Activity and Free Radical Scavenger Effects of Traditional Chinese Medicine Prescriptions Used for Stroke
Authors: Lin Chun-Ching , Yen Feng-Lin , Hsu Feng-Fang , Lin Jer-Min 
Published: October 2002

Abstract
The generation of oxygen radicals and lipid peroxidation may be factors in the cerebral damage secondary to ischaemia of the cerebrovascular disease, as in stroke. Five traditional Chinese medicinal prescriptions were investigated for their antioxidant activity: Shiee Fuu Jwu Iu Tang (TCMP1), Oh Yaw Shuen Chin Saan (TCMP2), Buu Yang Hwan Wim Tang (TCMP3), Sheau Shiuh Ming Tang (TCMP4), and Chir Hwu Jia Long Guu Mini Lih Tang (TCMP5).
Anti-lipid peroxidation, anti-superoxide formation and free radical scavenger activity were determined by the FeCl2—ascorbic acid-induced lipid peroxidation effects on lipids in-vitro, xanthine oxidase inhibition, cytochrome C system and an electron spin resonance spectrometer, respectively. The results showed that TCMP5 had greater anti-lipid peroxidation and anti-superoxide formation activity than the other prescriptions. TCMP4 had the greatest free radical scavenging effect, TCMP5 showed the greatest superoxide radical scavenger activity and TCMP3 showed the greatest hydroxyl radical scavenger activity. Tests were also performed to evaluate the effects of the five prescriptions on blood lipid in-vivo. The test showed that the prescriptions decreased the level of total cholesterol and LDL-cholesterol in serum in high cholesterol-fed rats.
From these results, it seems probable that these prescriptions may be effective in the prevention and therapy of stroke and ischaemia.
Endothelium-independent Vasorelaxant Effect of Dioclein, a New Flavonoid Isolated from Dioclea grandiflora, in the Rat Aorta
Authors: Trigueiro F , Côrtes S F , Almeida R N , Lemos V S 
Published: October 2002

Abstract
We have investigated the endothelium-independent vasorelaxant effect of the new Flavonoid dioclein (5,2′,5′-trihydroxy-6–7-dimethoxyflavanone) in the rat aorta.
In endothelium-denuded vessels, dioclein induced a concentration-dependent relaxation of aortic rings precontracted with noradrenaline (IC50 = 3.5 ± 0.89 times 10−4 M and KCl (IC50 = 5.2 ± 1.2 times 10−4 M). In the absence of extracellular calcium, dioclein reduced the contraction induced by noradrenaline (maximal reduction approximately 33%) but not that induced by caffeine. Dioclein also produced a concentration-dependent inhibition of the sustained contractions induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate in normal (IC50 = 4.0 ± 0.2 times 10−4 M) and Ca2+ -free solution (IC50 = 4.0 ± 0.3 times 10−4 M).
The results indicate that the endothelium-independent vasorelaxant effect of dioclein may be explained by inhibition of contractions dependent on activation of protein kinase C, voltage-dependent Ca2+ influx and on the release of intracellular Ca2+ stores sensitive to noradrenaline.
The Effect of Different Dosing Schedules of UCN-01 on its Pharmacokinetics and Cardiohaemodynamics in Dogs
Authors: Kurata N , Imabeppu S , Nitoh M , Kobayashi H , Kuwabara T , Kobayashi S 
Published: October 2002

Abstract
7-Hydroxy-staurosporine (UCN-01) is now under development as a novel anticancer drug. In clinical studies, different infusion schedules are being investigated in the USA and Japan. To examine the effect of different infusion schedules on the pharmacokinetics and cardiohaemodynamics of UCN-01, dogs were treated with UCN-01 as either a 3-h or a 24-h constant intravenous infusion. Blood pressure and heart rate, together with UCN-01 concentrations during and after infusion, were monitored. To analyse the relationship between the pharmacokinetics and cardiohaemodynamics of UCN-01, the plasma concentration of UCN-01 at the end of infusion (Cend), the area under the plasma concentration versus time curves (AUC0-∞) and the mean residence time (MRT) were used. As indices of cardiohaemodynamic changes, the area under decreasing systolic blood pressure and increasing heart rate versus time curves (dAUCpressure and AUCheart rate) were calculated by the trapezoidal method.
For the 3-h (0.22 and 0.65 mgkg−1) and 24-h infusion (0.81 to 6.48 mgkg−1), systolic and diastolic blood pressures fell after or during infusions, accompanied by a dose-dependent increase in heart rate for both infusions. During both infusion schedules, the plasma concentrations of UCN-01 gradually increased and Cend showed a dose-proportional increase. After that, UCN-01 was eliminated bi-exponentially with an elimination half-life of 5.14 ± 1.12 to 8.32 ± 1.80 h. The total clearance (CLtotal) ranged from 0.383 to 0.666 ± 0.149L h−1kg−1. There was no significant difference in these parameters among the doses in each infusion schedule, indicating that UCN-01 has a linear pharmacokinetic profile over the dose range examined for each infusion, and there were also no significant differences between the 3-h and 24-h infusion except for MRT. The pharmacokinetic parameters of Cend, AUC0-∞ and slope0-3h exhibited a degree of correlation with the AUCheart rate in the 3-h infusion and correlated significantly with the dAUCpressure in the 24-h infusion. The MRT did not correlate with cardiohaemodynamic changes during either infusion.
In conclusion, the pharmacokinetic profile of UCN-01 after the shorter infusion is similar to that after the longer one. However, a longer dosing period of UCN-01 increased the residence time in comparison with the shorter infusion. This may be due to the effect on the circulatory function in dogs.
Recombinant Human Lactoferrin is Effective in the Treatment of Helicobacter felis-infected Mice
Authors: Dial E J , Romero J J , Headon D R , Lichtenberger L M 
Published: October 2002

Abstract
Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis.
A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydro-phobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate.
These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application.
Effects ofUncaria tomentosaTotal Alkaloid and its Components on Experimental Amnesia in Mice: Elucidation Using the Passive Avoidance Test
Authors: Abdel-Fattah Mohamed A-F , Matsumoto Kinzo , Tabata Keiichi , Takayama Hiromitsu , Kitajima Mariko , Aimi Norio , Watanabe Hiroshi 
Published: October 2002

AbstractThe effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training.Uncaria tomentosa total alkaloid (10–20 mgkg−1, i.p.) and the alkaloid components (10–40 mg kg−1, i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mgkg−1, i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3mgkg−1, i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20mgkg−1, i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mgkg−1, i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mgkg−1, i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mgkg−1, i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam.These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.
Sustained Release of 5-Fluorouracil from Polymeric Nanoparticles
Authors: McCarron Paul A , Woolfson A David , Keating Siobhán M 
Published: October 2002

Abstract
The use of biodegradable nanoparticles loaded with 5-fluorouracil was investigated as a potential means to sustain the release of this drug. Nanoparticles prepared from four biodegradable polymers were loaded with 5-fluorouracil using three loading concentrations of drug and three different concentrations of added polymer.
Washing particles using a centrifugation/re-suspension with ultrasound protocol was found to dislodge the majority of drug, resulting in an over-estimation of incorporation efficiency and low levels of strongly entrapped drug. Increasing the initial 5-fluorouracil concentration before polymer/monomer addition increased the drug loading in both washed and unwashed particles. Increasing the amount of polymer used to make nanoparticles did not increase loadings, but did produce increased amounts of unusable polymer waste. Drug release from nanoparticles was evaluated using a Franz cell diffusion apparatus, which showed an initial burst effect followed by a slower release phase over 24 h. Indeed, nanoparticles prepared from poly(lactide-co-glycolide) released 66% of their 5-fluorouracil payload over this period.
It was concluded that 5-fluorouracil-loaded nanoparticles could be readily included into a hydrogel-based delivery system to provide sustained drug release for trans-epithelial drug-delivery applications.
Enhancement of Anti-metastatic Activity of Pentoxifylline by Encapsulation in Conventional Liposomes and Sterically Stabilized Liposomes in Murine Experimental B16F10 Melanoma Model
Authors: Sant V P , Nagarsenker M S , Rao S G A , Gude R P 
Published: October 2002

Abstract
Pentoxifylline has been shown to exhibit anti-metastatic activity by inhibiting homing of B16F10 melanoma cells in the murine experimental metastasis model. In this study, the effect of encapsulation of pentoxifylline in conventional and sterically stabilized liposomes on its anti-metastatic activity in the murine experimental metastasis model was investigated.
After a single intravenous dose (10, 20 or 40 mg kg−1), pentoxifylline solution, as well as conventional pentoxifylline liposomes, significantly reduced the number of pulmonary nodules compared with the untreated control group. Conventional pentoxifylline liposomes showed significantly higher inhibition (69%) of pulmonary tumour nodule formation at a dose of 20 mg kg−1 as compared with pentoxifylline solution (49%) at the same dose. Encapsulation of pentoxifylline in sterically stabilized liposomes prepared by incorporation of monomethoxypolyethyleneglycol (5000)-cholesteryl ester further enhanced the inhibition of pulmonary nodule formation (77%) at a dose of 20 mg kg−1 as compared with conventional pentoxifylline liposomes.
Overall, the results suggest that encapsulation of pentoxifylline in conventional liposomes enhanced its anti-metastatic activity. Steric stabilization of pentoxifylline liposomes also resulted in a two-fold increase in anti-metastatic activity (at dose of 10 mg kg−1) as compared with conventional liposomes.
Effect of Buthionine Sulphoximine, Glutathione and Methimazole on the Renal Disposition of Cisplatin and on Cisplatin-induced Nephrotoxicity in Rats: Pharmacokinetic-Toxicodynamic Analysis
Authors: Hanada Kazuhiko , Mukasa Yuji , Nomizo Yuko , Ogata Hiroyasu 
Published: October 2002

Abstract
The aim of this study was to classify the protective mechanisms of DL-buthionine-(S,-R-)-sulphoximine, glutathione and methimazole on cisplatin-induced nephrotoxicity in rats. An Emax model was used to study the effect of these compounds on the pharmacokinetics of cisplatin, especially renal handling and intra-renal biotransformation.
Cisplatin (5 mg kg−1) was administered as an intravenous bolus to rats treated with either 0–9% NaCl (control), buthionine sulphoximine, glutathione or methimazole. The blood urea nitrogen level was monitored to estimate cisplatin-induced nephrotoxicity. To estimate renal handling of cisplatin, cisplatin was infused intravenously to rats treated with 0–9% NaCl, buthionine sulphoximine, glutathione or methimazole. The concentrations of unchanged cisplatin in plasma, urine and kidney were determined by a post-column derivatization HPLC method. The relationship between the pharmacokinetics and toxicodynamics of cisplatin was analysed using a sigmoid Emax model.
All compounds studied ameliorated significantly the nephrotoxicity of cisplatin. The renal accumulation of cisplatin was reduced significantly by pretreatment with buthionine sulphoximine but not by either glutathione or methimazole. Although glutathione treatment did not affect the renal accumulation of cisplatin, it significantly decreased the binding of cisplatin to the intrarenal organelle and the decreased binding was well correlated to the decrease of the blood urea nitrogen level.
In summary, pharmacokinetic-toxicodynamic analysis will be useful for classifying the protective mechanism of cisplatin-induced nephrotoxicity.