bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine (“ecstasy”): is metabolism a contributory factor?
Authors: Forsling Mary , Fallon John K , Kicman Andrew T , Hutt Andrew J , Cowan David A , Henry John A 
Published: July 2003

Abstract
The aim of this investigation was to examine the effect of 3,4-methylenedioxymethamphetamine (MDMA) administration on arginine vasopressin (AVP) release. (R,S)-MDMA (40 mg) was administered to eight normally hydrated healthy male volunteers (22–32 years) and blood samples were collected up to 24 h. Plasma was assayed for AVP and cortisol by radioimmunoassays, and for MDMA and the N-demethylated metabolite, MDA, by gas chromatography-mass spectrometry. Sodium concentrations and osmolality were also determined. Plasma AVP increased in all subjects after MDMA administration and a significant negative correlation was observed between concentrations of AVP and both single and total enantiomer MDMA at 1 h (r &lt; −0.91, P &lt; 0.01). This had disappeared by 2 h (P &gt; 0.7). Compared with basal values, no significant change was observed for osmolality or cortisol at 1 h after drug administration. In conclusion, plasma AVP concentrations increase after MDMA administration, but the increase is not part of a generalized stress response since cortisol did not increase concurrently. A significant negative correlation between plasma MDMA and AVP was observed soon after administration. The possibility that a pharmacological effect of MDMA is primarily mediated via one or more metabolites, rather than by the parent drug, should be considered.
The effect of endotoxin on hepatocyte nuclear factor 1 nuclear protein binding: potential implications on CYP2E1 expression in the rat
Authors: Roe Amy L , Poloyac Samuel M , Howard Georgette , Shedlofsky Steven I , Blouin Robert A 
Published: July 2003

Abstract
The purpose of this study was to determine if changes in nuclear protein binding of hepatocyte nuclear factor 1 (HNF-1) occur after lipopolysaccharide (LPS) administration. In addition, the time-course of alterations in CYP2E1 regulation were evaluated. Rats were injected with 2.0 mg LPS and euthanized over a 72-h period. Nuclear protein binding to a consensus HNF-1 oligonucleotide was assessed by the electrophoretic mobility shift assay. CYP2E1 activity was analysed using chlorzoxazone as a substrate (6OH-CLZ), and CYP2E1 protein concentration was determined by enzyme-linked immunosorbent assay. Endotoxin treatment resulted in decreased nuclear protein binding to an HNF-1 element as early as 1 h after treatment and returned to control levels by 72 h. This reduced binding persisted for 24 h and returned to control values 48 h after LPS administration. In addition, the reduction in binding was primarily attributable to a HNF-1α immunoreactive protein. The observed reduction in HNF-1 binding was followed in the time-course by decreases in CYP2E1 activity and protein content with maximal decreases to 50 and 67% of control, respectively, at 48 h after LPS administration. Endotoxin is a potent inducer of the acute phase response (APR). The APR stimulation by endotoxin administration reduced HNF-1α binding and decreased the expression of CYP2E1 in the rat liver. The time-course of alterations in HNF-1 and CYP2E1 lend support to the possibility that HNF-1α may play a role in the down-regulation of genes that require HNF-1α for their constitutive expression. These data serve as an important precedent for future studies evaluating the direct association of decreased HNF-1α binding and reduced gene expression after LPS administration.
Antitumour activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumour-bearing mice
Authors: Kimura Yoshiyuki , Sawai Naoki , Okuda Hiromichi 
Published: July 2003

Abstract
We examined the antitumour activity and adverse reactions, such as myelotoxicity, gastrointestinal toxicity and body-weight loss, of the cancer chemotherapy drug doxorubicin when given with chitosan in sarcoma 180-bearing mice. Intraperitoneally administered doxorubicin (5 mg kg−1) given on days 1 and 8 with or without orally administered chitosan (200, 400 and 800 mg kg−1 twice daily) inhibited tumour growth. The orally administered chitosan (400 and 800 mg kg−1 twice daily) prevented doxorubicin-induced body-weight loss and small-intestinal mucosal injury. Similarly, the reduction of leucocyte number induced by the intraperitoneally administered doxorubicin was restored to normal by the oral administration of chitosan (400 and 800 mg kg−1 twice daily). It seems likely that the mechanisms by which the orally administered chitosan protects against doxorubicin-induced gastrointestinal toxicity may be due to the formation of doxorubicin-chitosan complex in the small-intestinal mucosa through the diffusion of chitosan into the small-intestinal villi. In conclusion, our data suggest that the oral administration of chitosan prevents the gastrointestinal mucositis associated with doxorubicin therapy.
Immunomodulating activity of CVT-E002, a proprietary extract from North American ginseng (Panax quinquefolium)
Authors: Wang Meiqi , Guilbert Larry J , Ling Lei , Li Jie , Wu Yingqi , Xu Sharon , Pang Peter , Shan Jacqueline J 
Published: July 2003

Abstract
The activity of CVT-E002, an aqueous extract containing mainly oligosaccharides and polysaccharides from North American ginseng (Panax quinquefolium), as an immunobooster on murine spleen cells and peritoneal macrophages, was studied in-vitro. CVT-E002 stimulated the proliferation of normal mouse spleen cells, of which the major responding subpopulation was identified as B lymphocytes. CVT-E002 also activated peritoneal exudate macrophages leading to enhanced interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and nitric oxide (NO) production. In addition, CVT-E002 stimulated in-vivo immunoglobulin G (IgG) production in treated mice. These results identify some of the immunomodulating activities of CVT-E002 and suggest its use clinically for the modulation of immune responses.
Protective effects of cannabinoid receptor agonists against cocaine and other convulsant-induced toxic behavioural symptoms
Authors: Hayase Tamaki , Yamamoto Yoshiko , Yamamoto Keiichi 
Published: July 2003

Abstract
Based on the previously reported co-localization and relationship between cannabinoid and dopamine receptors, the effects of cannabinoid receptor agonists against cocaine-induced toxic behavioural symptoms, including convulsive seizures, were examined in mice. The anticonvulsant effect of several cannabimimetics against seizures induced by other convulsants was also compared. The cannabinoid receptor agonists CP 55940 ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)-cyclohexanol) and WIN 55212–2 ((R)-(+)-[2.3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone), and the endogenous cannabinoid anandamide were co-administered intraperitoneally with cocaine (75 mg kg−1) or other convulsants such as bicuculline, methyl 6,7-dimethoxy-4-ethyl-β-carboline-carboxylate (DMCM), l-glutamic acid and N-methyl-d-aspartate (NMDA). CP 55940 (2.5 mg kg−1) and anandamide (15 mg kg−1) significantly antagonized cocaine-induced lethality, and CP 55940 and WIN 55212–2 (2.5 mg kg−1) significantly attenuated the severity of cocaine-induced convulsive seizures. Furthermore, ataxic hyperactivity, which was observed only in the cocaine-treated group of mice and could be evaluated by their activity counts, was also depressed in the groups of mice co-treated with each of the three cannabinoid agonists. However, none of these agonists protected against bicuculline- or DMCM-induced lethality or convulsive seizures. In contrast, all of the cannabinoid agonists, most notably anandamide, antagonized both l-glutamic acid (2 g kg−1)- and NMDA (200 mg kg−1)-induced convulsive seizures. These data support the previously reported close correlation between dopamine and cannabinoid receptors, and between cannabinoid agonists, especially anandamide, and glutamate (NMDA) receptors. Furthermore, these results suggest a potential therapeutic role for cannabinoid agonists against cocaine- and other-convulsant-induced toxicities.
New insights into the mechanism of action of the anti-inflammatory triterpene lupeol
Authors: Fernández Maria Angeles , de las Heras Beatriz , Garcia Maria Dolores , Sáenz Maria Teresa , Villar Angel 
Published: July 2003

Abstract
The pentacyclic triterpene lupeol has been studied for its inhibitory effects on murine models of inflammation and peritoneal macrophage functions in-vitro. Lupeol (0.5 and 1 mg/ear) administered topically suppressed the mouse ear oedema induced by 12-O-tetradecanoyl-phorbol acetate (TPA), being less effective on ear oedema induced by arachidonic acid. Quantitation of the neutrophil specific marker myeloperoxidase demonstrated that its topical activity was associated with reduction in cell infiltration into inflamed tissues. When tested in-vitro, lupeol significantly reduced prostaglandin E2 (PGE2) production from A23187-stimulated macrophages, but failed to affect leukotriene C4 release. It was a weak inhibitor of nitrite release, but dose-dependently suppressed PGE2. Cytokine production (tumour necrosis factor-α and interleukin-1β) was inhibited in the range 10–100 μm in lipopolysaccharide-treated macrophages. This study demonstrated that lupeol possessed anti-inflammatory activity which was likely to depend on its ability to prevent the production of some pro-inflammatory mediators.
Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats
Authors: Asad Mohammed , Shewade D G , Koumaravelou K , Abraham Benny K , Balasinor Nafisa , Ramaswamy S 
Published: July 2003

Abstract
The effect of hyperprolactinaemia, induced by two or four pituitary homografts under the kidney capsule, on gastric and duodenal ulcers has been studied. The acute gastric ulcer models used were pylorus ligation, indometacin-induced and ethanol-induced gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by mercaptamine hydrochloride. After pylorus ligation, there was an approximate 30–40% increase in gastric secretion, a significant increase in total acidity (P &lt; 0.01) and in the ulcer index (P &lt; 0.01) in rats bearing pituitary homografts under the kidney capsule when compared with the sham-operated control. Hyperprolactinaemia did not affect the formation of ethanol-induced gastric ulcers but showed a 40% reduction in the development of indometacin-induced gastric ulcers. It also produced a 20% increase in the ulcer index in acetic acid-induced chronic gastric ulcers and a 30% increase in ulcer area in mercaptamine-induced duodenal ulcers. Our results showed that hyperprolactinaemia induced gastric acid secretion and thereby aggravated gastric and duodenal ulcers in rats. Hyperprolactinaemia did not affect gastric cytoprotection.
Response of MCF-7 human breast cancer cells to some binary mixtures of oestrogenic compounds in-vitro
Authors: Suzuki Takahiro , Ide Kunihito , Ishida Masaru 
Published: July 2003

Abstract
The effects of simultaneous administration of some binary mixtures of seven natural and synthetic oestrogenic substances (17β-estradiol, estrone, bisphenol A, butylbenzyl phthalate, endosulfan, methoxychlor and pentachlorophenol) on the cellular proliferation of human breast cancer MCF-7 cells in-vitro (a modified E-screen assay) have been measured. To assess the presence or absence of interactions of the two agents, the data were analysed on the basis of a graphical method in which the types and extents of interactions were described by response-surface diagrams. Of the nine combinations of the agents examined, synergistic interaction was evident for the combination of 17β-estradiol and bisphenol A, whereas the remaining eight combinations were weakly synergistic, additive and/or weakly antagonistic in the dose-range tested.
Riluzole suppresses post-sigh, but not spontaneous apnoeas during sleep in rats
Authors: Radulovacki Miodrag , Pavlovic Sasa , Rakic Andrei , Janelidze Marika , Shermulis Lisa , Carley David W 
Published: July 2003

Abstract
We conducted this experiment to determine the role of glutamate in the mechanism of sleep apnoeas by administering riluzole, a glutamate release inhibitor, to freely moving rats in which sleep-related apnoeas are physiological phenomena. Adult Sprague-Dawley rats were implanted with electrodes for electroencephalogram (EEG) and electromyogram (EMG) recording to monitor sleep and were placed inside a single-chamber plethysmograph to monitor respiration. Sleep and respiration were recorded for 6 h following intraperitoneal administration of 0.5, 5.0 and 10.0 mg kg−1 riluzole. Riluzole dose-dependently suppressed post-sigh apnoeas during rapid eye movement (REM) sleep but had no effect on sleep-related spontaneous apnoeas. The drug (5.0 and 10.0 mg kg−1) also dose-dependently reduced wakefulness and increased sleep. It appears that glutamate, an excitatory neurotransmitter, plays a role in the genesis of the post-sigh apnoeas during REM sleep.
Synthesis and preliminary behavioural evaluation in mice of new 3-aryl-3-pyrrol-1-ylpropanamides, analogues of FGIN-1–27 and FGIN-1–43
Authors: Guillon J , Boulouard M , Lelong V , Dallemagne P , Rault S , Jarry C 
Published: July 2003

Abstract
The 2-aryl-3-indoleacetamides FGIN-1–27 and FGIN-1–43 have already been characterized in-vitro as potent and specific ligands for the mitochondrial DBI receptor. This affinity was associated with psychotropic properties in several rodent behavioural tasks (in particular anxiolytic action) via enhancement of GABA transmission through neurosteroid production. The synthesis of new 3-aryl-3-pyrrol-1-ylpropanamides 1a-i, analogues of FGIN-1–27 and FGIN-1–43, is described in four steps starting from the corresponding arylaldehydes. Preliminary evaluation of these compounds in behavioural studies (spontaneous locomotor activity and anxiolytic activity) in mice was also undertaken.
Hepatoprotective activity of Trichilia roka on carbon tetrachloride-induced liver damage in rats
Authors: Germanò M P , D'Angelo V , Sanogo R , Morabito A , Pergolizzi S , De Pasquale R 
Published: July 2003

Abstract
Trichilia roka Chiov. (Meliaceae) is a tree widely distributed in tropical Africa. It has been used in Mali folk medicine for the treatment of various illnesses. A decoction of the roots is taken as a remedy for colds and pneumonia, and it is used as a diuretic and in hepatic disorders. We have evaluated the hepatoprotective effects of a decoction of Trichilia roka root on CCl4-induced acute liver damage in rats. Treatment with the decoction showed a significant protective action made evident by its effect on the levels of glutamate oxalacetate transaminase and glutamate pyruvate transaminase in the serum, on the protein content and lipid peroxidation levels in the liver homogenate. Histopathological changes produced by CCl4, such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins, were clearly recovered by the treatment with Trichilia root decoction. On fractionating this extract into diethyl ether-soluble and water-soluble fractions, the activity was retained in the diethyl ether-soluble fraction. Moreover, the administration of decoction prevented a preferential deposition of collagen around the sinusoidal cell layer, which is responsible for the perisinusoidal fibrosis in the early stage of CCl4 damage. This study showed that treatment with Trichilia roka extracts or silymarin (as reference) appeared to enhance the recovery from CCl4-induced hepatotoxicity. The hepatoprotective properties of Trichilia roka may be correlated to polyphenol content of the decoction and its diethyl ether-soluble fraction.
Growth factor release from tissue engineering scaffolds
Authors: Whitaker M J , Quirk R A , Howdle S M , Shakesheff K M 
Published: July 2003

Abstract
Synthetic scaffold materials are used in tissue engineering for a variety of applications, including physical supports for the creation of functional tissues, protective gels to aid in wound healing and to encapsulate cells for localized hormone-delivery therapies. In order to encourage successful tissue growth, these scaffold materials must incorporate vital growth factors that are released to control their development. A major challenge lies in the requirement for these growth factor delivery mechanisms to mimic the in-vivo release profiles of factors produced during natural tissue morphogenesis or repair. This review highlights some of the major strategies for creating scaffold constructs reported thus far, along with the approaches taken to incorporate growth factors within the materials and the benefits of combining tissue engineering and drug delivery expertise.
Comparison of the lymphatic transport of a lipophilic drug from vehicles containing α-tocopherol and/or triglycerides in rats
Authors: Nielsen P B , Müllertz A , Norling T , Kristensen H G 
Published: July 2003

Abstract
The applicability of α-tocopherol as a lymphotropic carrier for a highly lipophilic drug has been evaluated. Transport to the intestinal lymph of the highly lipophilic model drug, Lu28–179, in rats after administration to the stomach in an α-tocopherol emulsion was compared with lymphatic transport after administration of a sesame oil emulsion and an α-tocopherol/sesame oil emulsion. Lymphatic transport of the triglycerides and of α-tocopherol was determined. A conscious rat model was used, and the mesenteric lymph was collected. There was no significant difference between the cumulative masses of triglyceride from the two emulsions containing triglyceride 24 h after administration. Administration of an α-tocopherol emulsion seemed to induce mobilization of endogenous triglyceride. The lymphatic transport of α-tocopherol was less than 1 mg 24 h after administration of both emulsions containing α-tocopherol. The absorption of Lu28–179 from the α-tocopherol emulsion was very low, with a lymphatic recovery of 0.05%. When administered in an α-tocopherol/sesame oil emulsion, the recovery of Lu28–179 increased sevenfold to 0.35%. However, after administration of Lu28–179 in a sesame oil emulsion, the lymphatic recovery increased a further 13-fold to 4.5%. In conclusion, the study showed that α-tocopherol did not promote lymphatic absorption of Lu28–179 and thus was not a good lymphotropic carrier, as compared with sesame oil. α-Tocopherol in combination with sesame oil was not a good lymphotropic carrier either. The non-absorbed α-tocopherol fraction in the intestine might be able to prevent the absorption of Lu28–179.
In-vitro nasal drug delivery studies: comparison of derivatised, fibrillar and polymerised collagen matrix-based human nasal primary culture systems for nasal drug delivery studies
Authors: Agu Remigius Uchenna , Jorissen Mark , Willems Tom , Augustijns Patrick , Kinget Renaat , Verbeke Norbert 
Published: July 2003

Abstract
The aim of this study was to establish a collagen matrix-based nasal primary culture system for drug delivery studies. Nasal epithelial cells were cultured on derivatised (Cellagen membrane CD-24), polymerised (Vitrogen gel) and fibrillar (Vitrogen film) collagen substrata. Cell morphology was assessed by microscopy. The cells were further characterised by measurement of ciliary beat frequency (CBF), transepithelial resistance (TER), permeation of sodium fluorescein, mitochondrial dehydrogenase (MDH) activity and lactate dehydrogenase (LDH) release upon cell exposure to sodium tauro-24, 25 dihydrofusidate (STDHF). Among the three collagen substrata investigated, the best epithelial differentiated phenotype (monolayer with columnar/cuboidal morphology) occurred in cells grown on Cellagen membrane CD-24 between day 4 and day 11. Cell culture reproducibility was better with Cellagen membrane CD-24 (90%) in comparison with Vitrogen gel (70%) and Vitrogen film (&lt; 10%). TER was higher in cells grown on Vitrogen gel than on Cellagen membrane CD-24 and Vitrogen film. The apparent permeability coefficient (Papp × 10−7 cm s−1) of sodium fluorescein in these conditions was 0.45 ± 0.08 (Vitrogen gel) and 1.91 ± 0.00 (Cellagen membrane CD-24). Except for LDH release, CBF and cell viability were comparable for all the substrata. Based on MDH activity, LDH release, CBF, TER and permeation studies, Cellagen membrane CD-24- and Vitrogen gel-based cells were concluded to be functionally suitable for in-vitro nasal drug studies. Vitrogen film-based cultures may be limited to metabolism and cilio-toxicity studies.
Ursodeoxycholic acid action on the transport function of the small intestine in normal and cystic fibrosis mice
Authors: Hardcastle J , Hardcastle P T , Chapman J , Taylor C J 
Published: July 2003

Abstract
Ursodeoxycholic acid possesses choleretic and cytoprotective properties and in cystic fibrosis (CF) it is used to treat the hepatobiliary symptoms of the disease. This study investigated the effects of this bile acid on the transport function of the small intestine in normal and CF mice. The effects of ursodeoxycholic acid were monitored as changes in short-circuit current (SCC) in stripped sheets of small intestine from normal (Swiss MF1) and transgenic CF (Cftrtm2Cam) mice. In ileal sheets from Swiss MF1 mice, mucosal ursodeoxycholic acid caused a biphasic increase in SCC. The first phase was reduced by lowering the mucosal Na+ concentration, while the second phase was inhibited by Cl−-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC), suggesting an initial Na+-dependent bile acid absorption followed by a stimulation of electrogenic Cl− secretion. Serosal application of ursodeoxycholic acid to the ileum and mucosal or serosal application to the mid-intestine and jejunum elicited a secretory response only. Secretion was Ca2+-dependent, but did not involve neural mechanisms. Mucosal mast cells, histamine and serotonin (5-HT) were implicated in the secretory response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 mice, but the secretory response to mucosal or serosal application of the bile acid was impaired in CF tissues. In ilea from CF mice the initial absorptive phase of the response to mucosal ursodeoxycholic acid was still observed. It is concluded that ursodeoxycholic acid induces secretion throughout the murine small intestine by a mechanism that involves degranulation of mucosal mast cells. In the ileum Na+-dependent absorption can also be detected. The secretory response is defective in CF intestine, but the absorptive effect is still present.