bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory effects of uraemic toxins 3-indoxyl sulfate andp-cresol on losartan metabolismin vitro
Authors: Tsujimoto Masayuki , Higuchi Keishi , Shima Daisuke , Yokota Hitoshi , Furukubo Taku , Izumi Satoshi , Yamakawa Tomoyuki , Otagiri Masaki , Hirata Sumio , Takara Kohji , Nishiguchi Kohshi 
Published: October 2010

AbstractObjectivesThe purpose of this study was to clarify the cause of decreased metabolic clearance of losartan in patients with end-stage renal failure. The influence of serum from haemodialysis patients (uraemic serum) and uraemic toxins on the metabolism of losartan to EXP-3174 was investigated in vitro.MethodsThe formation of EXP-3174 was estimated using pooled human liver microsomes. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid, hippuric acid, indole-3-acetic acid, 3-indoxyl sulfate and p-cresol were used as uraemic toxins.Key findingsUraemic serum potently decreased the formation of EXP-3174 in pooled human liver microsomes. In addition, 3-indoxyl sulfate and p-cresol significantly decreased the formation of EXP-3174 in a concentration-dependent manner. Furthermore, normal serum (10% v/v) with both 3-indoxyl sulfate and p-cresol (both 20 μmol/l) significantly decreased the formation of EXP-3174 by 46%, which was similar to the level of inhibition with uraemic serum (10% v/v).ConclusionsThese results suggest that decreased the metabolic clearance of losartan in patients with end-stage renal failure is partly due to high concentrations of 3-indoxyl sulfate and p-cresol.
Preparation, characterisation and anti-tumour activity of Ganoderma lucidum polysaccharide nanoparticles
Authors: Li Ni , Hu Yu-Lan , He Cai-Xia , Hu Cheng-Jie , Zhou Jun , Tang Gu-Ping , Gao Jian-Qing 
Published: October 2010

Abstract

Objectives
The aim was to prepare novel Ganoderma lucidum polysaccharide nanoparticles and to evaluate the physicochemical properties and anti-tumour activity in in-vitro cytotoxicity studies using HepG2, HeLa and A549 cancer cell lines, and growth promotion effects on mouse spleen cells.

Methods
Chitosan nanoparticles loaded with G. lucidum polysaccharide were prepared using the ion-revulsion method. The diameter distribution of the particles and the surface charge were measured using a zetasizer analyser. The entrapment efficiency and drug loading capacity were examined by the diethylaminoethanol weak anion exchange method. The cytotoxic effects of nanoparticles on tumour cells and the growth promotion effects on mouse spleen cells were tested using the MTT assay.

Key findings
Nanoparticles loaded with G. lucidum polysaccharide at 6 μg/ml and chitosan/sodium tripolyphosphate (mass) ratio of 5.5 had significantly greater cytotoxic effects on tumour cells and growth promotion effects on mouse spleen cells than empty nanoparticles.

Conclusions
G. lucidum polysaccharide nanoparticles showed significant anti-tumour efficacy, having both cytotoxic effects on tumour cells and growth promotion effects on spleen cells, making it a promising candidate in the clinical setting.
Polymer film formulations for the preparation of enteric pharmaceutical capsules
Authors: Smith Alan M , Ingham Andrew , Grover Liam M , Perrie Yvonne 
Published: October 2010

Abstract

Objectives
Standard pharmaceutical capsules are designed to dissolve in the acidic environment of the stomach releasing the encapsulated contents for absorption. When release is required further along the gastrointestinal tract capsules can be coated with acid insoluble polymers to enable passage through the stomach and dissolution in the intestine. This paper describes formulations that have the potential to be used to produce two-piece hard capsules for post-gastric delivery without the requirement of an exterior coat.

Methods
The formulation uses three polysaccharides: sodium alginate, hypromellose and gellan gum to provide acid insolubility and the ability to form capsules using standard industrial equipment.

Key findings
The rheological profile, on cooling, of the base material, water content and thickness of the films were shown to be comparable with those of commercial capsules. The capsules remained intact for 2 h in 100 mm HCl at pH 1.2, and within 5 min of being removed from the acid and submerged in phosphate-buffered saline at pH 6.8 were ruptured.

Conclusions
Selected formulations from this study have potential for use as delayed release capsules.
Repeated administration of oxycodone modifies the gene expression of several drug metabolising enzymes in the hepatic tissue of male Sprague-Dawley rats, including glutathione S-transferase A-5 (rGSTA5) and CYP3A2
Authors: Myers Alan L , Hassan Hazem E , Lee Insong J , Eddington Natalie D 
Published: October 2010

Abstract

Objectives
Clinical use and illicit abuse of the potent opioid agonist oxycodone has dramatically increased over the past decade. Yet oxycodone remains one of the least studied opioids, particularly its interactions on the genomic level. The aim of this study was to examine potential alterations in gene expression of drug metabolising enzymes in the liver tissue of male Sprague-Dawley rats chronically treated with oxycodone.

Methods
Rats were administered saline or oxycodone 15 mg/kg i.p. twice a day for 8 days. Changes in RNA levels were detected using microarray analysis validated by quantitative real-time PCR; consequent changes in protein expression and functionality were further assessed by Western blotting and activity assays.

Key findings
The expression of several drug metabolising enzymes was modulated by oxycodone treatment: cytochrome P450 (CYP) 2B2, CYP2C13, CYP17A1, epoxide hydrolase 2, carboxylesterase 2, flavin-containing monooxygenase 1, glutathione S-transferase alpha 5 (rGSTA5) and CYP3A2. In particular, the mRNA level of rGSTA5 (formerly GSTYc2) was up-regulated by approximately 6.5 fold and CYP3A2 was down-regulated by approximately 7.0 fold. Immunoblotting assays demonstrated a corresponding significant elevation of rGSTA5 protein and repression of CYP3A2 protein. The apparent cytosolic GST activity towards 1-chloro-2,4-dinitrobenzene conjugation and reduction of cumene hydroperoxide were significantly higher in liver from oxycodone-treated rats than that of saline-treated rats. In addition, the microsomal activity of CYP3A2, measured via 6β-hydroxylation of testosterone, was significantly decreased in oxycodone-treated rats.

Conclusions
Repeated oxycodone administration is associated with a significant up-regulation of rGSTA5 and concomitant down-regulation of CYP3A2 mRNA, protein expression and functionality. These results support further in-vivo studies into the clinical impact of our findings.
Antinociceptive and anti-inflammatory properties of 7-hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain
Authors: De Almeida Barros Taís A , De Freitas Luis A R , Filho José M B , Nunes Xirley P , Giulietti Ana M , De Souza Glória E , Dos Santos Ricardo R , Soares Milena B P , Villarreal Cristiane F 
Published: October 2010

AbstractObjectivesIn the present study we investigated the antinociceptive, anti-inflammatory and antipyretic effects of 7-hydroxycoumarin (7-HC) in animal models.MethodsThe effects of oral 7-HC were tested against acetic acid-induced writhing, formalin test, tail flick test, complete Freund's adjuvant (CFA)-induced hypernociception, carrageenan-induced paw oedema, lipopolysaccharide-induced fever and the rota rod test.Key findings7-HC (3–60 mg/kg) produced a dose-related antinociception against acetic acid-induced writhing in mice and in the formalin test. In contrast, treatment with 7-HC did not prevent thermal nociception in the tail flick test. A single treatment with 7-HC, 60 mg/kg, produced a long-lasting antinociceptive effect against CFA-induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7-HC produced a continuous antinociceptive effect against CFA-induced hypernociception. 7-HC (30–120 mg/kg) produced anti-inflammatory and antipyretic effects against carrageenan-induced inflammation and lipopolysaccharide-induced fever, respectively. Moreover, 7-HC was found to be safe with respect to ulcer induction. In the rota rod test, 7-HC-treated mice did not show any motor performance alterations.ConclusionsThe prolonged antinociceptive and anti-inflammatory effects of 7-HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.
Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis
Authors: Yoshioka Saburo , Hamada Atsuhide , Jobu Kohei , Yokota Junko , Onogawa Masahide , Kyotani Shojiro , Miyamura Mitsuhiko , Saibara Toshiji , Onishi Saburo , Nishioka Yutaka 
Published: October 2010

Abstract

Objectives
Non-alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non-alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non-alcoholic steatohepatitis.

Methods
The seed extract was given in the drinking water to fats being fed a methionine-choline-deficient diet for 15 weeks.

Key findings
Increases in alanine aminotransferase and aspartate aminotransferase levels were significantly inhibited in rats fed the seed extract compared with the group on the diet alone. Formation of fatty droplets in the liver was also inhibited. Antioxidant enzyme activity in liver tissue was higher than in the diet-only group and lipid peroxidation was reduced compared with rats that also received the extract. Expression of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal was lower in the rats given the seed extract than in the diet-only group. In the former, liver tissue levels of transforming growth factor-β and collagen were also decreased.

Conclusions
Thus, the E. japonica seed extract inhibited fatty liver, inflammation and fibrosis, suggesting its usefulness in the treatment of non-alcoholic steatohepatitis.
In-vitro and in-vivo antivenin activity of 2-[2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde against Ophiophagus hannah venom
Authors: Lattmann Eric , Sattayasai Jintana , Sattayasai Nison , Staaf Alexander , Phimmasone Sysaaht , Schwalbe Carl H , Chaveerach Arunrat 
Published: October 2010

Abstract

Objectives
Curcuma zedoaroides A. Chaveerach & T. Tanee, locally known as Wan-Paya-Ngoo-Tua-Mia, is commonly used in the North-Eastern part of Thailand as a ‘snakebite antidote’. The aim of this study was to isolate the active compound from the rhizome of C. zedoaroides, to determine its structure and to assess its antagonistic activity in vitro and in vivo against King cobra venom.

Methods
The active compound was obtained from C. zedoaroides by extraction with acetone followed by purification using column chromatography; its X-ray structure was determined. Its inhibition of venom lethality was studied in vitro in rat phrenic nerve-hemidiaphragms and in vivo in mice.

Key findings
The acetone extract of the Curcuma rhizomes contained a C20 dialdehyde, [2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde, as the major component. The isolated curcuma dialdehyde was found active in vitro and in vivo for antivenin activity against the King cobra venom.
Using isolated rat phrenic nerve-hemidiaphragm preparations, a significant antagonistic effect on the inhibition of neuromuscular transmission was observed in vitro. Inhibition on muscle contraction, produced by the 4 μg/ml venom, was reversed by 2–16 μg/ml of Curcuma dialdehyde in organ bath preparations over a period of 2 h. Mice intraperitoneally injected with 0.75 mg/kg venom and dialdehyde at 100 mg/kg had a significantly increased survival time. Injection of Curcuma dialdehyde (100 mg/kg) 30 min before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group.

Conclusions
The in vitro and in vivo evaluation confirmed the medicinal use of traditional snake plants against snakebites. The bioactivity is linked to an isolated molecule and not a result of synergistic effects of a mixture. The active compound was isolated and the structure fully elucidated, including its stereochemistry. This dialdehyde is a versatile chemical building block and can be easily obtained from this plant source.
Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus
Authors: Lee Bombi , Park Jongbong , Kwon Sunoh , Park Moo-Won , Oh Sang-Muk , Yeom Mi-Jung , Shim Insop , Lee Hye-Jung , Hahm Dae-Hyun 
Published: October 2010

Abstract

Objectives
The ameliorating effects of wild ginseng on learning and memory deficits were investigated in rats.

Methods
Rats were treated daily with wild ginseng or cultivated ginseng for 7 days at 30 min before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment by the administration of scopolamine, behavioural assessment using the Morris water maze was performed. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase and the reactivity of acetylcholinesterase in the hippocampus.

Key findings
Scopolamine injection induced impaired performance in the water maze test and severe cell losses in hippocampal cholinergic neurons, as indicated by decreased choline acetyltransferase immunoreactivity and increased acetylcholinesterase reactivity. Daily administration of wild ginseng produced a significant improvement in the escape latency for finding the platform in the Morris water maze and reduced the loss of cholinergic immunoreactivity in the hippocampus. The reduced expression of brain-derived neurotrophic factor mRNA due to the scopolamine injection was recovered to normal levels by the administration of wild ginseng.

Conclusions
Wild ginseng demonstrates a significant neuroprotective effect against scopolamine-induced neuronal and cognitive impairment.
3-Acetyl-11-keto-β-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity
Authors: Goel Amit , Ahmad Farhan Jalees , Singh Raman Mohan , Singh Gyanendra Nath 
Published: October 2010

AbstractObjectivesThe aim of this study was to develop 3-acetyl-11-keto-β-boswellic acid (AKBA)-loaded polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.MethodsPolymeric nanomicelles of AKBA were developed by a radical polymerization method using N-isopropylacrylamide, vinylpyrrolidone and acrylic acid. The polymeric nanomicelles obtained were characterized by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In-vitro and in-vivo evaluations of AKBA polymeric nanomicelles gel were carried out for enhanced skin permeability and anti-inflammatory and anti-arthritic activity.Key findingsTEM and DLS results demonstrated that polymeric nanomicelles were spherical with a mean diameter approximately 45 nm. FTIR data indicated a weak interaction between polymer and AKBA in the encapsulated system. The release of drug in aqueous buffer (pH 7.4) from the polymeric nanomicelles was 23 and 55% after 2 and 8 h, respectively, indicating sustained release. In-vitro skin permeation studies through excised abdominal skin indicated a threefold increase in skin permeability compared with AKBA gel containing the same amount of AKBA as the AKBA polymeric nanomicelles gel. The AKBA polymeric nanomicelle gel showed significantly enhanced anti-inflammatory and anti-arthritic activity compared with the AKBA gel.ConclusionsThis study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity.
Design, synthesis, characterization and in-vivo activity of a novel salmon calcitonin conjugate containing a novel PEG-lipid moiety
Authors: Cheng Weiqiang , Lim Lee-Yong 
Published: October 2010

AbstractObjectivesThe aim of the study was to explore (1) the synthesis of a novel poly(ethylene glycol) modified lipid (PEG-lipid, PL) containing a chemically active tri-block linker, ε-maleimido lysine (Mal), and its conjugation with salmon calcitonin (sCT), and (2) the biophysical properties and activity of the resulting conjugate, Mal-PL-sCT, relative to the control, 2PEG-Mal-sCT, which comprises sCT conjugated with α-palmitoyl-N-ε-maleimido-l-lysine at cysteine 1 and cysteine 7, and PEG moieties at lysine 11 and lysine 18 via a conventional stepwise method.MethodsThe PEG-lipid was obtained by condensing palmitic acid derivative of ε-maleimido lysine with methoxy poly(ethylene glycol) amine. Under reductive conditions, the PEG-lipid readily reacted with sCT to yield the resultant compound, Mal-PL-sCT.Key findingsDynamic light scattering analyses suggested that Mal-PL-sCT and 2PEG-Mal-sCT exhibited robust helical structures with a high tendency to aggregate in water. Both compounds were more stable against intestinal degradation than sCT, although Mal-PL-sCT was less stable than 2PEG-Mal-sCT. However, 2PEG-Mal-sCT did not possess hypocalcaemic activity while Mal-PL-sCT retained the hypocalcaemic activity of sCT when it was subcutaneously injected in the rat model. Multiple functional groups may be conjugated to a peptide via a tri-block linker without the risk of obliterating the intrinsic bioactivity of the peptide.ConclusionsThe resultant novel PEG-lipid has a potential role to optimize protein and peptide delivery.
Regional variations of vasomotion to G-protein coupled receptor agonists following heat stress in rats
Authors: Li Jie , Cao Yong-Xiao , Chen Kun-Lun , Cao Lei , Ma Zhao , Xu Cang-Bao 
Published: October 2010

AbstractObjectivesThis study was designed to compare vascular contractile and relaxing responses to G-protein coupled receptor agonists among the different regions of arteries following heat stress in rats.MethodsHeat exposure was performed by increasing the internal temperature of the rats to 42°C for 15 min. After heat stress for 48 h, a myograph system was used to monitor the contractile responses in rat renal, femoral and mesenteric arteries to agonists of endothelin type B (ETB) receptor, endothelin type A (ETA) receptor, serotonin receptor and α-adrenoceptor, respectively. In addition, calcitonin gene-related peptide (CGRP)-induced vasodilation was studied.Key findingsThe results showed that heat stress induced decreased contractions mediated by α-adrenoceptors and serotonin receptors (at lower concentration), while it increased contraction mediated by endothelin ETB receptors and enhanced relaxation mediated by CGRP receptors in the renal artery. Heat stress increased contractions mediated by endothelin ETB receptors, endothelin ETA receptors and α-adrenoceptors in the femoral artery. In the mesenteric artery, heat stress increased contractions mediated by endothelin ETB and serotonin receptors and relaxation mediated by CGRP receptors.ConclusionsThe vasomotor responses to the G-protein coupled receptor agonists with altered vascular contractions and relaxations were different in rat renal, femoral and mesenteric arteries after heat stress. This might have contributed to the redistribution of blood flow and aids understanding of the preconditioning phenomenon.
Bioavailability of lycopene in the rat: the role of intestinal lymphatic transport
Authors: Faisal Waleed , O'Driscoll Caitriona M , Griffin Brendan T 
Published: October 2010

Abstract

Objectives
As a natural antioxidant derived from dietary sources, lycopene has attracted considerable attention as a potent chemopreventative agent. Lycopene is an extremely lipophilic compound and absorption from dietary sources is estimated to be low and highly variable. As a result, plasma lycopene concentrations are poorly correlated with dietary intake of lycopene rich food stuffs. The development of an oral formulation remains a challenge that requires a better understanding of the mechanisms involved in the intestinal absorption of this compound.

Methods
The solubility of lycopene in simulated physiological fluids and bile salt mixed micelle formulations was determined. The extent of intestinal lymphatic transport and the absolute bioavailability of lycopene from a range of biorelevant media was evaluated in a mesenteric lymph duct cannulated anaesthetised rat model.

Results
The absolute bioavailability of lycopene after 8 h was 1.85 ± 0.39%. The overall extent of the intestinal lymphatic transport was in the range of 0.6–3.4% of the administered dose. A strong positive correlation (r2 &gt; 0.9) between intestinal lycopene levels and intestinal triglyceride levels was demonstrated.

Conclusions
The intestinal lymphatic route is the major uptake mechanism of lycopene from the gastrointestinal tract. Lycopene transport in intestinal lymph was closely associated with triglyceride transport in the lymph. Formulation strategies designed to promote intestinal lymphatic uptake, such as lipid-based formulations containing long-chain fatty acids (LCFA) or lecithin, may serve to enhance oral bioavailability of lycopene.
Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced acute injury in mice
Authors: Yang Lili , Dong Wen , Yan Fang , Ren Xiubao , Hao Xishan 
Published: October 2010

Abstract

Objectives
Toxicity caused by pharmacological and chemical substances, including carbon tetrachloride (CCl4), is a major pathological factor for liver injury. Therefore, strategies to prevent toxicity are needed for maintaining a healthy liver. This study was designed to determine whether recombinant bovine pancreatic trypsin inhibitor (rBPTI), a non-specific serine protease inhibitor, prevents CCl4-induced liver injury in mice.

Methods
Mice were treated with CCl4 in the presence or absence of co-treatment with rBPTI. Liver sections were prepared for histopathological assessment. Liver function was evaluated by detecting serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver index. Liver oxidative stress and inflammation were examined by detecting the liver malondialdehyde level and glutathione and superoxide dismutase activity, and serum tumour necrosis factor-α level, respectively.

Key findings
CCl4 induced hepatocyte necrosis, inflammatory cell infiltration and fatty degeneration, which were ameliorated by co-treatment with rBPTI in a concentration-dependent manner. Furthermore, rBPTI prevented CCl4-induced disruption of liver function. Importantly, rBPTI reduced CCl4-induced liver oxidative stress response and pro-inflammatory cytokine production.

Conclusions
These results indicated that rBPTI exerted a protective effect on CCl4-induced liver injury in mice. Thus, rBPTI may have potential application for prevention of liver injury induced by metabolism of drugs and toxic substances.