bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrastructural Alterations and DNA Synthesis of Renal Cell Nuclei following Cisplatin or Carboplatin Injection in Rats
Authors: Yasumasu Tetsuo , Ueda Toyofumi , Uozumi Jiro , Mihara Yukitaka , Koikawa Yasuhiro , Kumazawa Joichi 
Published: April 2011

Abstract
To clarify the difference in nephrotoxicity between cisplatin and carboplatin, ultrastructural alterations and DNA synthesis of renal cell nuclei were studied in Sprague-Dawley rats which had received intravenously either cisplatin or carboplatin at an equitoxic dose. Twelve hours after cisplatin injection, nucleolar segregation accompanied by aggregated nuclear heterochromatin was observed in the third segment of the proximal tubules. Seventy-two hours after cisplatin injection, nuclear damage was more widespread while regenerative cells were also observed. Nuclear damage was not observed in the carboplatin-treated rats. Nuclear DNA synthesis of renal cells was suppressed at 8, 12 and 24 h and was accelerated at 72 h after cisplatin injection. Carboplatin did not suppress nuclear DNA synthesis at any time. The results indicate that cisplatin, but not carboplatin, can affect the renal cell nuclei. Cisplatin-induced nephrotoxicity is related to its effects on renal cell nuclei.
Effect of Uraemia and Anephric State on the Pharmacokinetics of Tenoxicam in the Rat
Authors: Lopez-Bustamante L G , Troconiz J I F , Fos D 
Published: April 2011

Abstract
Renal alterations, uraemia and nephrotic syndrome induced in experimental animals caused a reduction in the plasma albumin concentration of 25 and 30%, respectively. As a result of this decrease, the unbound fraction of tenoxicam in uraemic rats (0·06 ± 0·02) and in anephric rats (0·11 ± 0·08) increased with respect to the control group (0·03±0·004). The induced hypoalbuminaemia did not modify the blood to plasma concentration ratio. Both plasma clearance (CL) and apparent volume of distribution at steady-state (Vdss) rose significantly with the increase in the unbound fraction: (Vdss 55 ±6 mL (control rats); 69 ± 12 mL (uraemic rats); 96 ± 30 mL (anephric rats); CL = 7± 1 mL h−1 (control rats); 12 ± 4 mL h−1 (uraemic rats); 15 ± 7 mL h−1 (anephric rats)). Tenoxicam elimination was found to be restrictive, with an extraction ratio less than 0·1 in the three groups. The induction of nephrotic syndrome was observed to have a significant effect on intrinsic metabolic activity, intrinsic clearance of tenoxicam being reduced by 30% in the anephric rats (161 ± 38 mL h−1) with respect to the values obtained in the control group (228 ± 22 mL h−1).
Pharmacokinetic Study of Gadolinium-DOTA in Control and Streptozocin Diabetic Rats
Authors: Michel A , Bonnet P A , Fernandez J P , Chambon C , Doucet D 
Published: April 2011

Abstract
The pharmacokinetics of gadolinium tetraazacyclododecanetetraacetic acid (Gd-DOTA), a contrast agent used in magnetic resonance imaging, have been evaluated in control and streptozocin-diabetic rats of different ages. In control rats, an age-related decrease in the Gd-DOTA elimination rate was noted, supported by a significantly lower apparent total body clearance and a significantly higher mean residence time. In diabetic rats, a similar but less important age-related change in the mean residence time and the apparent total body clearance was observed. Regardless of age-related differences in the pharmacokinetic parameters, a diabetic state induced several alterations in the Gd-DOTA pharmacokinetic parameters. The apparent total body clearance was significantly higher and the mean residence time significantly lower in diabetic rats indicating a higher elimination rate of Gd-DOTA. An important age-related increase in the volume of distribution at steady-state was noted in diabetic rats.
Binding of [3H]Haloperidol to Dopamine D2 Receptors in the Rat Striatum
Authors: Tsuchihashi Hiroshi , Sasaki Toko , Kojima Shigeko , Nagatomo Takafumi 
Published: April 2011

Abstract
The present study was designed to examine the properties of [3H]haloperidol binding to dopamine D2-receptors in rat striatum membranes, displacement potencies of various chemicals and differences between the affinities of various chemicals and two new 5-hydroxytryptamine (5-HT2) receptor antagonists, MCI-9042, (±)-2-(dimethylamino)-1-[[o-(m-methoxyphenetyl)phenoxy]methyl]ethyl hydrogen succinate hydrochloride and one of its metabolites. The plots of specific binding for the striatum membranes obtained from the Scatchard analysis using [3H]haloperidol were monophasic when nonspecific binding was determined with 10 μm chlorpromazine, and the Kd and Bmax values were 7·42±1·03 Nm and 1·58±0·20 pmol (mg protein)−1 (n= 10), respectively. The displacement potencies of D2 receptor, 5- HT2 receptor, histamine H1-receptor, and adrenoceptor antagonists were characterized by [3H]haloperidol binding to D2 receptors. The pKi values of a new antiplatelet agent, MCI-9042, and its metabolite were 5·02 and 5·53, respectively, and these values were lower than those of the D2-receptor antagonists, fluphenazine, spiperone, haloperidol, prochlorperazine, chlorpromazine, thioridazine, and sulpiride. They were also lower than the pKi values of the 5-HT2-receptor antagonists, pirenperone, ketanserin, methysergide, and mianserin. We conclude that the binding site of [3H]haloperidol in the rat striatum is the D2 receptor, that MCI-9042 and its metabolite have lower affinities for D2 receptors than for 5-HT2 receptors, and that this radioreceptor assay is useful for assessing the affinities of various agents.
The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5-hydroxytryptamine: in-vitro and ex-vivo studies
Authors: Ramassamy C , Christen Y , Clostre F , Costentin J 
Published: April 2011

Abstract
The Ginkgo biloba extract (EGb 761) added to a synaptosomal fraction prepared from mice cerebral cortex modified [3H]5-hydroxytryptamine ([3H]5-HT) uptake in a biphasic manner. Between 4 and 16 μg mL−1 EGb 761 increased significantly the [3H]-5-HT uptake (maximum + 23%). A similar increase was also obtained when synaptosomes were prepared from the cortex of mice treated orally with EGb 761, either acutely (100 mg kg−1, 14 h and 2 h before death) or semi-chronically (2× 100 mg−1 kg daily for 4 consecutive days). The in-vitro increase in [3H]5-HT uptake induced by EGb 761 was not observed in the presence of 10−6 m clomipramine, a 5-HT-uptake inhibitor. EGb 761 did not increase [3H]dopa-mine uptake by synaptosomes prepared from striatum of mice. We investigated different fractions of EGb 761 in order to determine the compounds inducing the increase in [3H]5-HT uptake. The BN 52063 extract (corresponding to the EGb 761 devoid of flavonoid substances) did not increase [3H]5-HT uptake. The Cp 202 extract (corresponding to the EGb 761 devoid of terpenic substances and containing mostly flavonoid substances) increased [3H]5-HT uptake. Among the flavonoids, quercetin has been tested and had no effect on the [3H]5-HT uptake. Since at the usual therapeutic doses of EGb 761, the effective concentrations of the components responsible for this increase are likely to be reached in the brain, one may suggest that this effect could contribute to the therapeutic effect of EGb 761.
Cross-linked Chitosan Microspheres: Preparation and Evaluation as a Matrix for the Controlled Release of Pharmaceuticals
Authors: Thanoo B Chithambara , Sunny M C , Jayakrishnan A 
Published: April 2011

Abstract
Chitosan microspheres having good spherical geometry and a smooth surface were prepared by the glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in paraffin oil using dioctyl sulphosuccinate as the stabilizing agent. Microspheres having different degrees of swelling were made by varying the cross-linking density. Microspheres were prepared by incorporating theophylline, aspirin or griseofulvin. Drug incorporation efficiencies exceeding 80% could be achieved for these drugs. In-vitro release studies of these drugs were carried out in simulated gastric and intestinal fluids at 37°C. It was observed that the drug release rates were influenced by the cross-linking density, particle size and initial drug loading in the microspheres.
Pharmacological Evaluation of the Histamine H1 and 5-HT Blocking Properties of 2-N-(Carboxamidinonormianserin) (FCC5): in-vitro studies
Authors: Leitch Ian M , Boura Alan L A , King Roger G 
Published: April 2011

Abstract
Some in-vitro pharmacological effects of a novel analogue of mianserin, 2-carboxamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2,-α) azepine hydrochloride (FCC5) have been studied. FCC5 was a non-competitive antagonist of both histamine-induced contractions of the guinea-pig ileum and 5-HT-induced contractions of rat fundal strips with pD'2 values of 6·13 and 5·57, respectively. The insurmountable antihistaminic effect of FCC5, 100 Nm, in the guinea-pig isolated ileum was not removed by washing. FCC5, 10–100 Nm, had no effect on responses to acetylcholine or barium chloride of the guinea-pig isolated ileum. In guinea-pig isolated right atria, FCC5, 1–30 μm, had no effect on H2-receptor-mediated chronotropic responses to histamine. FCC5, 10–1000 Nm, had no α2-adrenoceptor antagonist activity, as assessed by lack of effect on the inhibitory responses to B-HT 920 in the electrically stimulated rat isolated vas deferens. FCC5 resembles mianserin by being a potent, non-competitive antagonist at histamine H1 and 5-HT receptors, but differs from mianserin in a number of respects including having much less effect at α2-adrenoceptors.
Non-opioid-dependent Inhibitory Action of Loperamide on Cholinergic Neurotransmission in Canine Isolated Bronchial Smooth Muscle
Authors: Tamaoki Jun , Horii Satsuki , Katayama Michio , Yamawaki Isao , Takizawa Takao 
Published: April 2011

Abstract
The effect of loperamide on cholinergic neurotransmission in canine bronchial smooth muscle was studied under isometric conditions in-vitro. Addition of loperamide decreased contractile responses to electrical field stimulation in a dose-dependent fashion, the maximal decrease from the control response and the IC50 value being 65·4 ± 5·9% and 1·5 μm, respectively. In contrast, loperamide was without effect on the responses to exogenously administered acetylcholine. The inhibitory effect of loperamide was not altered by pre-incubation of tissues with propranol, 6-hydroxydopamine, bicuculline, or naloxone. These results suggest that loperamide attenuates the neurally mediated airway contraction probably by inhibiting acetylcholine release from cholinergic nerve terminals through a non-opioid-dependent mechanism.
Stimulation of faecal excretion in rats by α2-adrenergic antagonists
Authors: Croci Tiziano , Bianchetti Alberto 
Published: April 2011

Abstract
The effects of several α-adrenoceptor antagonists on faecal output and water content in rats were investigated. Fed rats were treated either subcutaneously (s.c.) or orally with phentolamine, idazoxan, yohimbine, 1-(2-pyrimidinyl) piperazine (PmP) or prazosin. Drug potencies were compared on the basis of the dose inducing excretion of 1 g dry weight of faeces (AD1) by rats that do not normally excrete any faecal pellet during the observation time. The α2-antagonist, idazoxan (AD1 = 0·25 mg kg−1, s.c.) was approximately 2·5, 4 and 8 times more potent than PmP, phentolamine and yohimbine in promoting faecal excretion. Prazosin, an α1-antagonist with putative affinity for the α2B-receptor subtype, was the least effective (AD1 &gt; 5 mg kg−1, s.c). The same compounds also increased the water content of faeces and had similar potencies by the oral route. Both clonidine (0·15 mg kg−1, s.c.) and atropine (0·2 mg kg−1, s.c.) significantly prevented the effects of all antagonists on faecal excretion. The present results are consistent with the view that rat colon is under tonic inhibitory control of prejunctional α2-adrenergic receptors, whose blockage by specific antagonists induces faecal excretion. The α2A-receptor subtype appears to be the most likely candidate for controlling faecal excretion through inhibition of acetylcholine release.
The potent irritancy of the daphnane orthoester, resiniferatoxin, exhibits features of a mixed aetiology
Authors: Evans A Tudor , Gordge Philip C , Sahni Vaneeta , Evans Fred J 
Published: April 2011

Abstract
Resiniferatoxin-induced erythema of mouse ear was shown to possess characteristics of both a phorbol ester-mediated response and that induced by the neurogenic irritant, capsaicin. Whereas the response to the phorbol ester, sapintoxin D, was delayed and prolonged, and was augmented by capsaicin pretreatment, the response to resiniferatoxin was biphasic, with the early phase being antagonized by capsaicin desensitization. However, resiniferatoxin was most potent in inducing a delayed erythema which, unlike the capsaicin response, was sensitive to inhibition by low dose hydrocortisone treatment, but not to chronic capsaicin desensitization. It is concluded that the erythema response to resiniferatoxin has a mixed aetiology, which may explain the unique potency of this toxin.
Quantitative Skin Blanching Assay of Corticosteroid Creams Using Tristimulus Colour Analysis
Authors: Chan Sui Yung , Po Alain Li Wan 
Published: April 2011

Abstract
The potencies of four proprietary corticosteroid creams were ranked using blanching measured by a tristimulus colour analyser as an index. Intra-subject variation was measured in a trial using a single subject while in a second study inter-subject variation was quantified using six volunteers. Discriminative parameters were derived from the extended multiple-point chromaticity coordinates L* and a* recorded after application of the steroid creams under occlusion. Analysis of variance of the data using the linear regression model was followed by Tukey's multiple comparison tests. Ranking of the creams using parameters of the pharmacodynamic response corresponded with the generally accepted rank order of the potencies of the corticosteroid creams. It is proposed that this multiple-point skin blanching assay of topical corticosteroids using an internationally accepted clear measurement standard and the subsequent data analysis be adopted as a standard protocol.
The Pharmacology of a Novel Topical Retinoid, BMY 30123: Comparison with Tretinoin
Authors: Tramposch K M , Nair X , Gendimenico G J , Tetrault G B , Chen S , Kiss I , Whiting G , Bonney R J 
Published: April 2011

Abstract
Preclinical studies pertaining to the pharmacology and toxicology of BMY 30123 (4-acetamidophenyl retinoate) are reported. BMY 30123 is a novel compound which has topical retinoid activity. This compound exhibits lower toxicity, both local and systemic, than other clinically used topical retinoids such as tretinoin (all-trans retinoic acid) in animal models. BMY 30123 is effective in a number of retinoid sensitive skin models including the rhino mouse utriculi reduction assay, the mouse epidermal hyperplasia model and in the suppression of DNA synthesis in mouse skin stimulated with phorbol ester. BMY 30123 was equipotent with tretinoin in these topical models. In the rhino mouse model the ED30 values for BMY 30123 and tretinoin were 0·037 and 0·015 Mm, respectively. In addition, BMY 30123 was active in the UVB-induced photodamaged mouse model, another retinoid sensitive model. One of the problems associated with topically applied tretinoin is local irritation. Therefore, for topical therapy to be optimal, it is important to reduce or minimize local irritation. Repeated applications of BMY 30123 to rabbit skin resulted in low skin irritation. The first perceptible signs of skin irritation produced by BMY 30123 occurred at a dose 10 times higher than that observed for tretinoin. BMY 30123 also exhibits low retinoid activity after oral or i.p. administration in mice and produced no signs of hypervitaminosis A-related toxicity at twenty times the no effect dose of tretinoin. Because retinoids are effective modulators of epidermal growth and differentiation, this compound should be useful for the treatment of cutaneous disorders that exhibit altered epidermal differentiation such as acne, psoriasis, ichthyosis and epithelial tumours. While BMY 30123 and tretinoin are shown here to be equipotent in animal efficacy models, the low skin irritation activity gives BMY 30123, at a minimum, a 10-fold enhancement in the therapeutic index relative to tretinoin and suggests that retinoid efficacy and skin irritation are separable phenomena.
Parthenolide Content and Bioactivity of Feverfew (Tanacetum parthenium (L.) Schultz-Bip.). Estimation of Commercial and Authenticated Feverfew Products
Authors: Heptinstall S , Awang D V C , Dawson B A , Kindack D , Knight D W , May J 
Published: April 2011

Abstract
Three physicochemical methods (HPLC, NMR spectroscopy, and HPLC of a derivative) have been used to measure parthenolide in authenticated Tanacetum parthenium (feverfew) and in several commercial purported feverfew products. A bioassay based on inhibition of the secretory activity of blood platelets by extracts of feverfew in comparison with parthenolide was also used. Similar results were obtained for all three physicochemical assays and also for the bioassay. Thus different methodologies yield consistent values for parthenolide content of feverfew preparations. Parthenolide appears to be mainly responsible for the antisecretory effects of extracts of feverfew. Authenticated Tanacetum parthenium grown in the UK contained a high level of parthenolide in leaves, flowering tops and seeds but a low level in stalks and roots. The level of parthenolide in powdered leaf material fell during storage. The purported feverfew products varied widely in their parthenolide content and in some products parthenolide was not detected. Possible reasons for the variation in parthenolide content are discussed. Since therapeutic efficacy has only been demonstrated for preparations of feverfew that contain parthenolide, it is suggested that manufacturers of feverfew products should use measurements of parthenolide as a means of standardization and quality control.
Demonstration of the Receptor-mediated Hepatic Uptake of Dextran in Mice
Authors: Nishikawa Makiya , Yamashita Fumiyoshi , Takakura Yoshinobu , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
To establish a rationale of designing a drug targeting system using dextran conjugation, the disposition behaviour of dextran itself was investigated in mice. At a high dose (100 mg kg−1), [14C]dextran was retained in the blood circulation for a considerably long period. However, [14C]dextran rapidly disappeared from the plasma and accumulated in the liver (up to 60% of dose in 1 h) after a dose of 1 mg kg−1. Cellular localization of [14C]dextran in the liver following intravenous administration was examined and the contribution of parenchymal cells was demonstrated as well as the case of galactosylated bovine serum albumin (Gal-BSA). Pharmacokinetic analysis based on a physiological model including Michaelis-Menten type uptake mechanisms revealed that the Michaelis constant Km,l of [14C]dextran was 100 times greater than that of Gal-BSA. Coadministration of Gal-BSA delayed the hepatic uptake of [14C]dextran and the simulation based on the physiological model suggested that [14C]dextran was taken up by the same mechanism as Gal-BSA. These results suggested that dextran conjugation of a drug might lead to its undesirable accumulation in the liver at a low dose and an appropriate modification of dextran, such as carboxymethylation, would be required in such cases.
Interaction and Aggregation of Sodium Aurothiomalate and Poly l-Lysine
Authors: Brown Robert A , Wells Terri M 
Published: April 2011

Abstract
This report describes the interaction and aggregation of sodium aurothiomalate with polylysine, a potentially useful property, both as a model for drug-protein interaction and as a means of reversibly immobilizing sodium aurothiomalate. Sodium aurothiomalate formed stable precipitates with polylysine at neutral pH, ionic strengths below 1m NaCl, and optimally, at sodium aurothiomalate to lysine ratios of less than one. The interaction could be demonstrated both by precipitation (which was sensitive to the size of polylysine polymer) and by using polylysine immobilized to Sepharose. Precipitation could be inhibited by addition of the organic thiomalate moiety alone. These findings indicate that the interaction of sodium aurothiomalate with polylysine is by electrostatic bonding of the thiomalate (mercaptosuccinate) moiety and the ε-amino groups of lysine residues. At suitable molar ratios this will link together many polylysine chains leading to precipitation. This represents a potentially valuable interaction for immobilization of the drug and in the formation of conjugates.
Doxorubicin-loaded Casein Microspheres: Protean Nature of Drug Incorporation
Authors: Willmott N , Magee G A , Cummings J , Halbert G W , Smyth J F 
Published: April 2011

Abstract
We have studied incorporation of [14C]doxorubicin within protease-sensitive casein microspheres both by 14C-activity, measuring total drug, and HPLC, measuring free drug only. It was found that total drug content (27·7 μg mg−1) exceeded free drug content (3·2 μg mg−1) suggesting that the major portion of doxorubicin was incorporated via a covalent linkage to matrix protein. In-vivo drug disposition and activity studies suggested that this fraction of doxorubicin was the major species within tumour tissue (total vs free: 5 min, 14·3 μg g−1 vs 0·7 μg g−1; 24 h, 11·7 μg g−1 vs 1.1 μg g−1;48 h, 11·2 μg g−1 vs 1·2 μg g−1; 72 h, 100 μg g−1 vs 0·8 μg g−1), did not exhibit a ‘burst’ effect, was slowly cleared (30% loss over 3 days), and was equiactive (growth delay = 12 days) compared with drug in solution (growth delay = 10 days). This work clearly implicates in-vivo microsphere matrix biodegradation in drug release and subsequent disposition and activity.
Anti-ulcer Activity of a Slow-release Zinc Complex, Zinc Monoglycerolate (Glyzinc)
Authors: Rainsford K D , Whitehouse M W 
Published: April 2011

Abstract
A slow-release zinc complex, zinc monoglycerolate (ZMG) was examined for its potential gastroprotective activity in various gastric ulcer models. These models comprised (a) oral or parenteral nonsteroidal anti-inflammatory drugs (NSAIDs) given to rats whose gastrointestinal mucosa was pre-sensitized by prior development of arthritis, oleyl alcohol-induced inflammation and cold exposure, (b) oral ethanol (12·5−100%) with and without added 4% HCl, (c) intraperitoneal reserpine (5 mg kg−1) in arthritic and normal rats and in normal mice, (d) oral NSAIDs given to mice in which acid and pepsin production was stimulated by co-administration of intraperitoneal bethanechol chloride (5 mg kg−1) to enhance ulcer development, and (e) NSAIDs given to carrageenan-inflamed rats to determine effects of ZMG on paw inflammation. In these models, ZMG given orally was effective in preventing development of gastric lesions, except with propionic acid NSAIDs; the effective doses being apparently dependent on the severity of the mucosal injury. In many of the models ZMG was superior to zinc sulphate and other zinc salts or metal ion complexes investigated but was slightly more effective or equipotent compared with zinc acexamate. ZMG did not impair the anti-oedemic effects of NSAIDs. ZMG is thus an effective agent in preventing ulcer development in a wide range of model systems and may be more effective than zinc salts because of the controlled slow-release of zinc from the complex.