bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice
Authors: Capasso Anna , Loizzo Alberto 
Published: July 2003

Abstract
The effects of dexamethasone pretreatment on clonidine-induced antinociception and locomotor hypoactivity were investigated in mice. In the hot-plate and the tail-flick tests, dexamethasone administered intraperitoneally at a dose of 1 mg kg−1, 30, or 60 min before clonidine, reduced clonidine antinociception in both tests and reduced clonidine-induced locomotor hypoactivity in the activity cage. When administered 15 min before clonidine, dexamethasone had no effect on clonidine antinociception. A higher dexamethasone dose (10 mg kg−1) induced the same effects observed at a dose of 1 mg kg−1 in the hot-plate and the tail-flick tests, but the former dose had a stronger effect on locomotor hypoactivity. Dexamethasone (10 ng/mouse) administered intracerebroventricularly 30 min before clonidine was also able to reduce both clonidine-induced antinociception and locomotor hypoactivity. The protein synthesis inhibitor, cycloheximide, administered intraperitoneally at the dose of 10 mg kg−1, 2, h before clonidine, was able to prevent dexamethasone effects on clonidine-induced antinociception. The glucocorticoid receptor antagonist RU-38486, administered intracerebroventricularly at the dose of 1 ng/mouse, was also able to block dexamethasone effects on clonidine-induced antinociception and locomotor hypoactivity, whereas both cycloheximide and RU-38486 per se did not influence pain sensitivity or locomotor activity. These results suggest that the dexamethasone effects on clonidine-induced antinociception and locomotor hypoactivity depend on the stimulating effects that dexamethasone exert, on the protein synthesis via the glucocorticoid receptor in the brain.
The development and in-vitro evaluation of novel mixed metal hydroxy-carbonate compounds as phosphate binders
Authors: Rankin B J , Zhu H , Webb M , Roberts N B 
Published: July 2003

Abstract
The currently available phosphate binders are relatively inefficient and suffer from clinical side-effects of increased absorption of calcium and aluminium and the diarrhoea-inducing effects of magnesium. A new class of compounds based on mixed metal hydroxides has been developed and evaluated for their potential as phosphate binders. The mixed metal hydroxides were prepared using a standard procedure for hydrotalcite (Al2Mg6(OH)16. CO3. 4H2O) by substituting Fe3+ for Al3+ with Mg3+ or Ca2+ as the divalent metal ion. Phosphate precipitation (binding) was examined at different pH values in aqueous solution and in various food mixtures in comparison with hydrotalcite, Al(OH)3, CaCO3 and Mg(OH)2 on the same weight-to-weight basis. A series of compounds with differing ratios of metal ions (Fe:Mg/Ca 1:2 or 1:3) gave analytically similar ratios to those predicted from the initial amounts added. CTFeCa bound &gt; 90% phosphate in aqueous solution compared with 65% binding with CTFeMg, 85% binding with Mg(OH)2, and less than 30% binding for CaCO3 and Al(OH)3. The mixed metal compounds also bound up to 80 % phosphate in various food matrices, which was relatively independent of changes in pH, compared with Mg(OH)2, where binding decreased from 85% at pH 3.0 to 25% at pH 8.0. Al(OH)3 and CaCO3 were relatively ineffective phosphate binders under all the conditions tested. The mixed metal hydroxides compounds show considerable promise as phosphate binders over those currently available and warrant further patient-based in-vivo testing.
1,8-Cineole protects against liver failure in an in-vivo murine model of endotoxemic shock
Authors: Santos Flávia A , Silva Regilane M , Tomé Adriana R , Rao Vietla S N , Pompeu Margarida M L , Teixeira Maria J , De Freitas Luiz A R , De Souza Valderes L 
Published: July 2003

Abstract
The effects of 1,8-cineole on d-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg−1, i.p.) and LPS (5 μg kg−1, i.p.) greatly elevated serum concentrations of tumour necrosis factor-α (TNF-α), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg−1, p.o.) and dexamethasone (1 mg kg−1, s.c.),60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-α and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPS-induced liver injury through the inhibition of TNF-α production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies.
The evaluation of novel mixed metal hydroxy-carbonates as phosphate binders: an in-vivo study in the rat
Authors: Rankin B J , Thewles A , Lote C J , Webb M , Roberts N B 
Published: July 2003

Abstract
A number of novel phosphate binders based on mixed metal hydroxide structures incorporating Fe and Ca, or Fe and Mg (classified as CT, Crosfield test compounds), were compared with the established phosphate binders Mg(OH)2, Al(OH)3, CaCO3 and a commercial hydrotalcite (Al- and Mg-based) using a rat model. The changes in urine and soluble faecal phosphate were used to evaluate efficacy of phosphate binding. The binders were mixed into a standard rat maintenance food at a concentration of 1% (w/w). Four rats were used for each binder study group and fed over 7 days. Urine and faeces were collected (in a metabolic cage) over the last 24-h study period and the phosphate content measured. The urinary phosphate was significantly reduced (P &lt; 0.001) with CTFeCa (72 ± 44 μm), CTFeMg (13 ± 4 μm), CT100 (26 ± 11 μm), and Mg(OH)2 (65 ± 53 μm), compared with control (766 ± 188 μm), Al(OH)3 (1256 ± 279 μm), and CaCO3 (857 ± 25 μm). The soluble phosphate content of the faeces was significantly reduced (P &lt; 0.05) by up to 60% with CTFeCa, CTFeMg and Mg(OH)2, and up to 40% with CT100 and Al(OH)3, compared with 30% in controls and 10% with CaCO3. The new mixed metal hydroxy-carbonate compounds based on FeCa or FeMg are effective phosphate binders in-vivo and warrant further testing in patients.
Antinociceptive effect of U-50488H, a κ-opioid agonist, in streptozotocin-induced diabetic mice
Authors: Suzuki Yasuyuki , Goto Kazuhiro , Shiizaki Kazuhiro , Omiya Yuji , Ishige Atsushi , Komatsu Yasuhiro , Kamei Junzo 
Published: July 2003

Abstract
We compared the antinociceptive activity of a κ-opioid agonist, U-50488H, in streptozotocin-induced diabetic mice with that in non-diabetic mice. Subcutaneously administered U-50488H (3 and 10 mg kg−1) showed a more potent antinociceptive effect, as evaluated by the tail-pressure method, in diabetic mice than in non-diabetic mice. Increased antinociceptive activity of U-50488H observed in diabetic mice was also observed in mice given U-50488H intrathecally (3 and 10 μg). However, there were no differences observed between diabetic and non-diabetic mice given U-50488H intracerebroventricularly (3 and 10 μg). Although the antinociceptive effect of U-50488H (3 mg kg−1, s.c.) in non-diabetic mice was increased by treatment with PD135158 (100 ng, i.c.v.), a cholecystokininB (CCKB) antagonist, the antinociceptive activity of U-50488H which was enhanced in diabetic mice was not influenced by PD135158. Moreover, the increased antinociceptive activity of U-50488H (3 mg kg−1, s.c.) in diabetic mice diminished when desulfated octapeptide of cholecystokinin (3–100 ng, i.c.v.), a CCKB agonist, was administered. These results suggested that diabetic mice were selectively hyper-responsive to spinal κ-opioid receptor-mediated antinociception. The function of the analgesia inhibitory system in which cholecystokinin is used as a transmitter might be diminished in diabetic mice.
Effect of γ-butyrobetaine on fatty liver in juvenile visceral steatosis mice
Authors: Higashi Yasuhiko , Yokogawa Koichi , Takeuchi Noriko , Tamai Ikumi , Nomura Masaaki , Hashimoto Noriyoshi , Hayakawa Jun-Ichiro , Miyamoto Ken-Ichi , Tsuji Akira 
Published: July 2003

Abstract
We pharmacokinetically examined the effect of γ-butyrobetaine, a precursor of l-carnitine, on the change of fatty acid metabolism in juvenile visceral steatosis (JVS) mice, which have systemic l-carnitine deficiency due to lack of l-carnitine transporter activity. The concentrations of total free fatty acid (FFA), palmitic acid and stearic acid in the liver of JVS mice were significantly higher than those in wild-type mice. After intravenous administration of γ-butyrobetaine (50 mg kg−1), the concentration of l-carnitine in the plasma of JVS mice reached about twice that of the control level and levels in the brain, liver and kidney were also significantly increased, whereas those in wild-type mice hardly changed. Although the plasma concentrations of FFA in both types of mice were unchanged after administration of γ-butyrobetaine, the concentrations of palmitic acid and stearic acid were significantly decreased. In particular, the liver concentration of FFA in JVS mice was decreased to the wild-type control level, accompanied by significant decreases in long-chain fatty acids, palmitic acid and stearic acid, whereas those in wild-type mice were not changed. These results suggest that γ-butyrobetaine can be taken up into organs, including the liver, of JVS mice, and transformed to l-carnitine. Consequently, administration of γ-butyrobetaine may be more useful than that of l-carnitine itself for treatment of primary deficiency of carnitine due to a functional defect of the carnitine transporter.
The lipid-lowering effect of trans-dehydrocrotonin, a clerodane diterpene from Croton cajucara Benth. in mice fed on high-fat diet
Authors: Silva Regilane M , Santos Flávia A , Rao Vietla S N , Maciel Maria A M , Pinto Angelo C 
Published: July 2003

Abstract
The clerodane diterpene trans-dehydrocrotonin extracted and isolated from the stem bark of Croton cajucara Benth. was investigated for its lipid-lowering effect in mice fed on a high-fat diet. Mice fed on a high-fat diet for a two-week period demonstrated significantly increased blood levels of total cholesterol and triglycerides, compared with normal controls. Oral treatment with trans-dehydrocrotonin at a dose of 25 or 50 mg kg−1 daily markedly suppressed the high-fat-diet associated rise in total cholesterol and triglyceride levels. The hypocholesterolaemic effect of trans-dehydrocrotonin was more prominent at the dose of 50 mg kg−1 with significant decreases in high-density lipoprotein, very-low-density lipoprotein and low-density lipoprotein cholesterol levels. The lower atherogenic index of the trans-dehydrocrotonin-treated groups suggests the hypolipidaemic potential of this plant-based drug. These results indicate that orally administered trans-dehydrocrotonin is effective in suppressing high-fat-diet-induced hyperlipidaemia in mice and suggest its likely beneficial use as anti-atherogenic agent.
Interactions among proteins and hydrophobically modified polyelectrolytes
Authors: Bromberg L E 
Published: July 2003

Abstract
A special class of hydrophobically modified polyelectrolytes was studied wherein poly(acrylic acid) (PAA) was conjugated with Pluronic F127 NF surfactant. The Pluronic-PAA copolymer solutions form gels at low concentrations when exposed to body temperature. Such gels possess enhanced retention in topical applications. Circular dichroism spectra indicate that tertiary structures of human insulin, haemoglobin, and albumin were stabilized in solutions of Pluronic-PAA. Aggregation of insulin in gelled solutions of Pluronic-PAA was impeded as demonstrated in shaking tests. The presence of Pluronic-PAA hindered the insulin degradation by α-chymotrypsin by at least 7-fold. Extraction of calcium ions from trypsin by Pluronic-PAA led to the dramatic changes in the tertiary structure and total loss of enzymatic activity, suggesting that Pluronic-PAA could inhibit tryptic degradation of proteins.
Turbidimetric and HPLC assays for the determination of formulated lysozyme activity
Authors: Liao Yong-Hong , Brown Marc B , Martin Gary P 
Published: July 2003

Abstract
In several studies lysozyme has been employed as a model protein to investigate the effects of formulation factors upon biological activity. The aim of this work was to develop and validate an HPLC technique to assay lysozyme and to compare the results with biological activity determined from a validated turbidimetric assay. The turbidimetric assay was based upon the lytic action of lysozyme on Micrococcus lysodeikticus cells, whilst the reverse-phase HPLC assay employed an acetonitrile gradient in 0.1% trifluoroacetic acid. The limits of detection and quantification were 3.84 and 6.24 μg mL−1 for HPLC assay, whilst the corresponding values for turbidimetric assay were 1.94 and 3.86 μg mL−1. The methods were used to monitor the loss of enzyme activity after heating. Lysozyme concentrations determined from HPLC peak height were found to correlate (r2 = 0.9963) with those obtained from turbidimetric assay.
Pro-inflammatory activity of contaminating DNA in hyaluronic acid preparations
Authors: Filion Mario C , Phillips Nigel C 
Published: July 2003

Abstract
Hyaluronic acid (HA), an abundant non-sulfated glycosaminoglycan component of the extracellular matrix, has applications in drug delivery, tissue engineering and as an ingredient in cosmetics. HA preparations containing high-molecular-weight polymers are also used in the treatment of inflammatory disorders such as arthritis and interstitial cystitis. Low-molecular-weight fragments derived from HA have been reported to induce pro-inflammatory cytokines such as IL-12 and TNF-α, and could therefore potentially exacerbate existing inflammation. We therefore examined the pro-inflammatory activity of HA preparations, since inflammatory reactions are known to occur following administration of HA. We tested low-molecular-weight fragments obtained from seven different HA preparations, either by sonication (≅ 3 times 105 Da) or by hyaluronidase digestion (≅ 1 times 104 Da), for the ability to induce the synthesis of IL-12 and TNF-α by human monocytic cells. We found that two of the seven HA preparations tested stimulated the synthesis of IL-12 and TNF-α by human monocytic cells. We unexpectedly found that the induction of IL-12 and TNF-α by these HA preparations was not due to their degradation to low-molecular-weight fragments, since their native high-molecular-weight forms possessed the same ability to stimulate IL-12 and TNF-α synthesis, but was due to the presence of contaminating DNA. Treatment of these two HA preparations with deoxyribonuclease I abrogated or reduced the induction of IL-12 and TNF-α. It is clear from this study that HA preparations can induce the synthesis of pro-inflammatory cytokines by monocytes. The ability of HA to act as a pro-inflammatory mediator may not, however, be related to the presence of low-molecular-weight HA fragments, but to the presence of DNA. The presence of pro-inflammatory DNA in HA preparations should be evaluated before its use, not only for the treatment of patients with inflammatory disorders, but also before many other applications.
Cryptofolione derivatives from Cryptocarya alba fruits
Authors: Schmeda-Hirschmann Guillermo , Astudillo Luis , Bastida Jaume , Codina Carles , De Arias Antonieta Rojas , Ferreira María Elena , Inchaustti Alba , Yaluff Gloria 
Published: July 2003

Abstract
Cryptofolione (1) and the new cryptofolione derivative 6-(4,6-dimethoxy-8-phenyl-octa-1,7-dienyl)-4-hydroxy-tetrahydro-pyran-2-one (2) were isolated from the fruits of Cryptocarya alba. The structures were elucidated by spectroscopic methods. Cryptofolione showed activity towards Trypanosoma cruzi trypomastigotes, reducing their number by 77% at 250 μg mL−1. Cryptofolione showed moderate cytotoxicity in both macrophages and T. cruzi amastigotes. It also displayed a mild inhibitory effect on the promastigote form of Leishmania spp. As both cytotoxic and trypanocidal effects are similar, the compound presented little selectivity in our assay models.
Tea consumption modulates hepatic drug metabolizing enzymes in Wistar rats
Authors: Maliakal Pius P , Coville Peter F , Wanwimolruk Sompon 
Published: July 2003

Abstract
The antioxidant, antimutagenic and anticarcinogenic activities of green tea and its polyphenols have been reported. As bioactivation of the precarcinogens and detoxification of ultimate carcinogens are mainly carried out by hepatic metabolizing enzymes, we have investigated the modulation of these enzyme activities subsequent to tea consumption in rats. Female Wistar rats were divided into eight groups (n = 5). Six groups were given aqueous solutions (2%, w/v) of six different teas (New Zealand green tea, Australian green tea, Java green tea, Dragon green tea, Gunpowder green tea or English Breakfast black tea) as the sole source of fluid. One group was given a standard green tea extract (0.5%, w/v) while the control group had free access to water. At the end of four-weeks treatment, different cytochrome P450 (CYP) isoform and phase II enzyme activities were determined by incubation of the liver microsomes or cytosols with appropriate substrates. CYP 1A2 activity was markedly increased in all the tea treatment groups (P &lt; 0.05). CYP 1A1 activity was increased significantly in most of the groups except for the Madura, Gunpowder, and Java green tea-treatment groups. Cytosolic glutathione-S-transferase activity was significantly increased (P &lt; 0.05) in the New Zealand, Gunpowder, and Java green tea-treatment groups. The microsomal UDP-glucuronosyl transferase activity remained unchanged or was moderately increased in most of the groups. The balance between the phase I carcinogen-activating enzymes and the phase II detoxifying enzymes could be important in determining the risk of developing chemically-induced cancer.
Buchu (Agathosma betulina and A. crenulata, Rutaceae) essential oils: their pharmacological action on guinea-pig ileum and antimicrobial activity on microorganisms
Authors: Lis-Balchin M , Hart S , Simpson E 
Published: July 2003

Abstract
The mode of action of essential oils from two buchu species (Agathosma betulina and A. crenulata, Rutaceae) from the Cape region of South Africa has been studied on smooth muscle in-vitro using guinea-pig ileum. At high concentration, the oils had an initial spasmogenic activity followed by spasmolysis. The spasmolytic action was post-synaptic, not atropine-like and did not involve adrenoceptor or guanylyl cyclase activation. In the presence of the phosphodiesterase inhibitor rolipram, the spasmolytic action of A. betulina was significantly increased whilst that due to A. crenulata was also increased but not to a significant level. These results suggested a mode of action for the oils involving cyclic adenosine monophosphate. In addition, A. betulina appeared to block calcium channels but this was not seen with A. crenulata, possibly because the initial spasmogenic activity complicated the study of its spasmolytic action. Neither essential oil (10 μL, undiluted) demonstrated antimicrobial action against Enterococcus hirae and Pseudomonas aeruginosa but very low activity was observed against Escherichia coli, Saccharomyces cerevisiae and Staphylococcus aureus, suggesting little potential for these oils as antimicrobial agents/preservatives.
Ethnopharmacology in drug discovery: an analysis of its role and potential contribution
Authors: Heinrich Michael , Gibbons Simon 
Published: July 2003

Abstract
In this paper we discuss some examples of ethnopharmacological research as it has been conducted during the last two centuries and look at the current role of this discipline in drug discovery (especially with respect to the American and European markets) and the further development of these phytotherapeutical resources for local use in the countries of origin (ethnopharmacology). Examples from 19th century research on curare (Humboldt and Bernard), from the 20th century on hallucinogenic mushrooms (Wasson), on Mexican Indian indigenous plants (our own research) and of current industry based research are used to illustrate the development of this discipline and to highlight the challenges for the future.
Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55
Authors: Terao T , Matsuda K , Shouji H 
Published: July 2003

Abstract
Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100–55), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6–7 by the addition of NaOH. The Eudragit L100–55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100–55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9 ± 0.1 to 5.7 ± 0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81 ± 0.42 μg mL−1 vs 0.63 ± 0.08 μg mL−1. However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100–55. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100–55, to 21.4 ± 4.0 μg h mL−1 from 13.3 ± 3.9 μg h mL−1, and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100–55 to rats. These findings clearly demonstrate that the addition of Eudragit L100–55 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100–55.