bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hesperetin, a citrus flavonoid, on bacterial enzymes and carcinogen-induced aberrant crypt foci in colon cancer rats: a dose-dependent study
Authors: Aranganathan Selvaraj , Selvam Jayabal Panneer , Nalini Namasivayam 
Published: October 2010

Abstract
Hesperetin, an important bioactive compound in Chinese traditional medicine, has antioxidant and anticarcinogenic properties. Hesperetin is found in abundance in orange and grape juices (200–590 mg L−1) consumed in the daily diet. We have investigated the effect of different doses of hesperetin on faecal and colonic mucosal bacterial enzymes and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. The rats were divided into six groups and were fed a modified pellet diet for 16 weeks. Group 1 served as control and group 2 received the modified pellet diet along with hesperetin (30 mg kg−1). The rats in groups 3–6 rats were given a weekly subcutaneous injection of DMH (20 mg kg−1) for the first four weeks. Hesperetin was supplemented orally at different doses (10, 20 or 30 mg kg−1) for a total of 16 weeks. At the end of the experimental period all rats were killed. In DMH-treated rats, the activity of faecal and colonic mucosal bacterial enzymes, such as β-glucuronidase, β-galactosidase, β-glucosidase, nitroreductase, sulfatase and mucinase, were significantly elevated, but in rats supplemented hesperetin along with DMH the activity was significantly lowered (P &lt; 0.05). The total number of aberrant crypts was significantly increased in unsupplemented DMH-treated rats, while hesperetin supplementation to DMH-treated rats significantly reduced the total number of crypts. The results demonstrated that hesperetin supplementation at a dose of 20 mg kg−1 played a potent role in suppressing the formation of aberrant crypt foci and reducing the activity of bacterial enzymes in colon cancer.
Adenosine A2A receptors and their role in drug addiction
Authors: Brown Robyn M , Short Jennifer L 
Published: October 2010

AbstractThe specific events between initial presumably manageable drug intake and the development of a drug- addicted state are not yet known. Drugs of abuse have varying mechanisms of action that create a complex pattern of behaviour related to drug consumption, drug-seeking, withdrawal and relapse. The neuromodulator adenosine has been shown to play a role in reward-related behaviour, both as an independent mediator and via interactions of adenosine receptors with other receptors. Adenosine levels are elevated upon exposure to drugs of abuse and adenosine A2A receptors are enriched in brain nuclei known for their involvement in the processing of drug-related reinforcement processing. A2A receptors are found in receptor clusters with dopamine and glutamate receptors. A2A receptors are thus ideally situated to influence the signalling of neurotransmitters relevant in the neuronal responses and plasticity that underlie the development of drug taking and drug-seeking behaviour. In this review, we present evidence for the role of adenosine and A2A receptors in drug addiction, thereby providing support for current efforts aimed at developing drug therapies to combat substance abuse that target adenosine signalling via A2A receptors.
Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine
Authors: de Araujo Daniele Ribeiro , Cereda Cintia Maria Saia , Brunetto Giovanna Bruschini , Vomero Viviane Urbini , Pierucci Amauri , Neto Humberto Santo , de Oliveira Alexandre Leite Rodrigues , Fraceto Leonardo Fernandes , Braga Angélica de Fátima de Assunção , de Paula Eneida 
Published: October 2010

Abstract
This study reports an investigation of the pharmacological activity, cytotoxicity and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and α-tocopherol (4:3:0.07, mole%). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. Cytotoxicity was evaluated by the tetrazolium reduction test using sciatic nerve Schwann cells in culture. Local anaesthetic activity was assessed by mouse sciatic and rat infraorbital nerve blockades. Histological analysis was performed to verify the myotoxic effects evoked by RVC formulations. Plain (RVCPLAIN) and liposomal RVC (RVCLUV) samples were tested at 0.125%, 0.25% and 0.5% concentrations. Vesicle size distribution showed liposomal populations of 370 and 130 nm (85 and 15%, respectively), without changes after RVC encapsulation. The partition coefficient value was 132 ± 26 and in-vitro release assays revealed a decrease in RVC release rate (1.5 fold, P &lt; 0.001) from liposomes. RVCLUV presented reduced cytotoxicity (P &lt; 0.001) when compared with RVCPLAIN. Treatment with RVCLUV increased the duration (P &lt; 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4–1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVCPLAIN. Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVCPLAIN or RVCluv at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVCLUV as a potential new formulation, since RVC is a new and safe local anaesthetic agent.
Oroxylin A induces G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells
Authors: Yang Yong , Hu Yang , Gu Hong-Yan , Lu Na , Liu Wei , Qi Qi , Zhao Li , Wang Xiao-Tang , You Qi-Dong , Guo Qing-Long 
Published: October 2010

Abstract
We reported previously that oroxylin A, a natural product isolated from Scutellariae Radix, was a potent apoptosis inducer of human hepatoma HepG2 cells. In this study, cell-cycle arrest of BGC-823 human gastric carcinoma cells caused by oroxylin A has been investigated. Based on our 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and flow cytometric analysis, treatment of BGC-823 cells with growth suppressive concentrations of oroxylin A caused an irreversible arrest in the G2/M phase of the cell cycle. Western blot analysis demonstrated that oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2). The results suggested that oroxylin A induced G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells.
Taxifolin glycoside inhibits dendritic cell responses stimulated by lipopolysaccharide and lipoteichoic acid
Authors: Kim Yun Jeong , Choi Sun Eun , Lee Min Won , Lee Chung Soo 
Published: October 2010

Abstract
Antigen-presenting dendritic cells may play an important role in the pathogenesis of atopic dermatitis. Taxifolin is demonstrated to have anti-inflammatory effects. The present study was designed to assess the effect of taxifolin glycoside against stimulated responses of dendritic cells isolated from mouse bone marrow and spleen. Dendritic cells exposed to lipopolysaccharide, lipoteichoic acid or interleukin (IL)-1β exhibited increased production of IL-12 p70 and tumour necrosis factor alpha, increased formation of reactive oxygen species (ROS) and nitric oxide (NO), and elevation of intracellular Ca2+ levels. Treatment with taxifolin glycoside inhibited responses stimulated by the microbial products or IL-1β in dendritic cells in a dose-dependent manner. Taxifolin glycoside had a significant inhibitory effect on the production of cytokines, formation of ROS and NO, and change in intracellular Ca2+ levels in dendritic cells of bone marrow and spleen. The results show that taxifolin glycoside seems to inhibit the dendritic cell responses stimulated by microbial products and IL-1β, suggesting that taxifolin glycoside may exert an inhibitory effect against dendritic-cell-mediated immune responses.
Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs
Authors: Crumb William , Benyamina Amine , Arbus Christophe , Thomas George P , Garay Ricardo P , Hameg Ahcène 
Published: October 2010

Abstract
Monodesmethyl cyamemazine and cyamemazine sulfoxide, the two main metabolites of the antipsychotic and anxiolytic phenothiazine cyamemazine, were investigated for their effects on the human ether-à-go-go related gene (hERG) channel expressed in HEK 293 cells and on native INa, ICa, Ito, Isus or IK1 of human atrial myocytes. Additionally, cyamemazine metabolites were compared with terfenadine for their effects on the QT interval in anaesthetized guinea pigs. Monodesmethyl cyamemazine and cyamemazine sulfoxide reduced hERG current amplitude, with IC50 values of 0.70 and 1.53 μM, respectively. By contrast, at a concentration of 1 μM, cyamemazine metabolites failed to significantly affect INa, Ito, Isus or IK1 current amplitudes. Cyamemazine sulfoxide had no effect on ICa at 1 μM, while at this concentration, monodesmethyl cyamemazine only slightly (17%), albeit significantly, inhibited ICa current. Finally, cyamemazine metabolites (5 mg kg−1 i.v.) were unable to significantly prolong QTc values in the guinea pig. Conversely, terfenadine (5 mg kg−1 i.v.) significantly increased QTc values. In conclusion, cyamemazine metabolite concentrations required to inhibit hERG current substantially exceed those necessary to achieve therapeutic activity of the parent compound in humans. Moreover, cyamemazine metabolites, in contrast to terfenadine, do not delay cardiac repolarization in the anaesthetized guinea pig. These non-clinical findings explain the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use.
Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels
Authors: Huang Liping , Abuhamdah Sawsan , Howes Melanie-Jayne R , Dixon Christine L , Elliot Mark S J , Ballard Clive , Holmes Clive , Burns Alistair , Perry Elaine K , Francis Paul T , Lees George , Chazot Paul L 
Published: October 2010

Abstract
Both Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils have putative anti-agitation properties in humans, indicating common components with a depressant action in the central nervous system. A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically validated essential oil derived from La, which has shown clinical benefit in treating agitation. La inhibited [35S] TBPS binding to the rat forebrain gamma aminobutyric acid (GABA)A receptor channel (apparent IC50 = 0.040 ± 0.001 mg mL−1), but had no effect on N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or nicotinic acetylcholine receptors. A 50:50 mixture of Mo and La essential oils inhibited [3H] flunitrazepam binding, whereas the individual oils had no significant effect. Electrophysiological analyses with rat cortical primary cultures demonstrated that La reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01–1 mg mL−1), whereas no inhibition of NMDA- or AMPA-induced currents was noted. La elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classic GABAA antagonist picrotoxin which evoked profound epileptiform burst firing in these cells). These properties are similar to those recently reported for Mo. The anti-agitation effects in patients and the depressant effects of La we report in neural membranes in-vitro are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here. These data suggest that components common to the two oils are worthy of focus to identify the actives underlying the neuronal depressant and anti-agitation activities reported.
Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery
Authors: Gordon Sarah , Saupe Anne , McBurney Warren , Rades Thomas , Hook Sarah 
Published: October 2010

Abstract
In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised. The immunostimulatory capacity of these vaccine delivery systems was assessed in-vitro and in-vivo. Particle sizing measurements and SEM images showed that optimised OVA-loaded CNP had a size of approximately 200 nm, a polydispersity index &lt; 0.2, and a positive zeta-potential of approximately 18 mV. The amount of OVA adsorbed onto CNP was high with an adsorption efficacy of greater than 96%. Raman spectroscopy indicated conformational changes of OVA when adsorbed onto the surface of CNP. Uptake of the dispersions and immunological activation of murine dendritic cells in-vitro could be demonstrated. Investigation of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with &lt; 10% of total protein being released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo.
Modulating effect of polyethylene glycol on the intestinal transport and absorption of prednisolone, methylprednisolone and quinidine in rats by in-vitro and in-situ absorption studies
Authors: Shen Qi , Li Wenji , Lin Yulian , Katsumi Hidemasa , Okada Naoki , Sakane Toshiyasu , Fujita Takuya , Yamamoto Akira 
Published: October 2010

AbstractThe effects of polyethylene glycol 20000 (PEG 20000) on the intestinal absorption of prednisolone, methylprednisolone and quinidine, three P-glycoprotein (P-gp) substrates, across the isolated rat intestinal membranes were examined by an in-vitro diffusion chamber system. The serosal-to-mucosal (secretory) transport of these P-gp substrates was greater than their mucosal-to-serosal (absorptive) transport, indicating that their net movement across the intestinal membranes was preferentially in the secretory direction. The polarized secretory transport of these drugs was remarkably diminished and their efflux ratios decreased in the presence of PEG 20000. In addition, PEG 20000 did not affect the transport of Lucifer yellow, a non-P-gp substrate. The intestinal membrane toxicity of PEG 20000 was evaluated by measuring the release of alkaline phosphatase (ALP) and protein from the intestinal membranes. The release of ALP and protein was enhanced in the presence of 20 mM sodium deoxycholate (NaDC), a positive control, while these biological parameters did not change in the presence of 0.1–5% (w/v) PEG 20000. These findings indicated that the intestinal membrane damage caused by PEG 20000 was not a main reason for the enhanced absorptive transport of these P-gp substrates in the presence of PEG 20000. Furthermore, the transepithelial electrical resistance (TEER) of rat jejunal membranes in the presence or absence of PEG 20000 was measured by a diffusion chamber method. PEG 20000 (0.1–5.0 % w/v) did not change the TEER values of the rat jejunal membranes, indicating that the increase in the absorptive transport of these P-gp substrates might not be due to the increased transport of these P-gp substrates via a paracellular pathway caused by PEG 20000. Finally, the effect of PEG 20000 on the intestinal absorption of quinidine was examined by an in-situ closed-loop method. The intestinal absorption of quinidine was significantly enhanced in the presence of 0.1-1.0% (w/v) PEG 20000. These findings suggest that PEG 20000 might be a useful excipient to improve the intestinal absorption of quinidine, which is mainly secreted by a P-gp-mediated efflux system in the intestine.
Mechanisms involved in the antinociceptive effect caused by diphenyl diselenide in the formalin test
Authors: Savegnago Lucielli , Jesse Cristiano R , Santos Adair R S , Rocha João B T , Nogueira Cristina W 
Published: October 2010

AbstractThis study investigated the mechanisms involved in the antinociceptive action induced by diphenyl diselenide ((PhSe)2) in the formalin test. Mice were pre-treated with (PhSe)2 by the oral route (0.1–100 mg kg−1), 30 min before formalin injection. To address some of the mechanisms by which (PhSe)2 inhibits formalin-induced nociception mice were treated with different drugs. The antinociceptive effect of (PhSe)2 was shown in the first and second phases of the formalin test. The antinociceptive effect caused by (PhSe)2 (10 mg kg−1, p.o.) was prevented by intrathecal injection of K+ channel blockers such as apamin and charybdotoxin (small- and large-conductance Ca2+-activated K+ channel inhibitors, respectively) and tetraethylammonium (TEA, a non-selective voltage-dependent K+ channel inhibitor), but not glib-enclamide (an ATP-sensitive K+ channel inhibitor). The antinociceptive action caused by (PhSe)2 (10 mg kg−1, p.o.) was also blocked by a nitric oxide (NO) synthase inhibitor (Nω-nitro-l-arginine, L-NOARG) and the soluble guanylate cyclase inhibitors 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and methylene blue. These results suggest the participation of NO/cyclic GMP/Ca2+ and K+ channel pathways in the antinociceptive effect caused by (PhSe)2.
Cancer, chitosan nanoparticles and catalytic nucleic acids
Authors: Tan Mei Lin , Choong Peter F M , Dass Crispin R 
Published: October 2010

AbstractObjectivesThe aim of this review was to examine gene therapy involving DNAzyme and siRNA encapsulation into chitosan nanoparticles, discussing the current and future status of this drug delivery system in enhancing drug delivery and cancer therapy.Key findingsCancer is a disease state in which the cells in our body undergo mutations at the genetic level and are transformed, acquiring the ability to replicate limitlessly. Conventional cancer treatment involves the use of surgery and cytotoxic chemotherapy and/or radiotherapy, which have the potential of harming normal, otherwise healthy, non-neoplastic cells. Newer forms of therapy such as immunotherapy and gene therapy have shown initial promise, but still require better ways to limit exposure to cancerous lesions in the body. As a result drug delivery systems have been developed in attempts to deliver therapeutics specifically to the target lesion site. One recent drug delivery system has revolved around the use of chitosan nanoparticle technology, where therapeutics are encapsulated into nanoparticles and targeted to tumours.SummaryThough few, attempts at encapsulating therapeutics such as deoxyribozymes and small or short interfering RNA have been optimistic and encouraging.
Hydrogen sulfide protects from intestinal ischaemia–reperfusion injury in rats
Authors: Liu Hao , Bai Xiao-Bin , Shi Song , Cao Yong-Xiao 
Published: October 2010

Abstract

Objectives
Hydrogen sulfide (H2S) is an endogenously gaseous mediator, regulating many pathophysiological functions in mammalian cells. H2S has been shown to inhibit myocardial ischaemia–reperfusion (I/R) injury. However, little is known about whether H2S could modulate intestinal I/R injury. This study aimed to investigate the effect of H2S on intestinal I/R injury and potential mechanism(s) underlying the action of H2S in regulating the development of intestinal I/R injury in rats.

Methods
Following surgical induction of intestinal I/R injury for 1 h, groups of Sprague-Dawley rats were treated with, or without, tetramethylpyrazine (8 mg/kg), or sodium hydrosulfide (NaHS, an H2S donor at 7 or 14 μmol/kg) 30 min after occlusion. All rats were sacrificed immediately after the reperfusion. Their intestinal injury, together with that of sham-control rats, was histologically examined and their sera and intestinal malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (GSH-Px) activities were characterized by biochemical analysis.

Key findings
The results showed that NaHS significantly reduced intestinal I/R injury and the levels of sera and intestinal MDA activity, and dramatically increased the levels of serum and intestinal SOD and GSH-Px activity.

Conclusions
The results suggest that H2S protects from intestinal I/R injury in rats, which is associated with increase in the activity of antioxidant enzymes.
Effect of Guanxin No.2 decoction on gene expression in different areas of the myocardial infarcted heart of rats using microarray technology
Authors: Zeng Xiaowei , Yang Jun , Yang Xianzhe , Hong Dongsheng , Wu Limao , Yu Jun 
Published: October 2010

Abstract

Objectives
We have used microarray technology to detect the effect of Guanxin No.2 decoction on gene expression in different areas of the myocardial infarcted heart of rats.

Methods
Male Sprague-Dawley rats (180–200 g) were randomly divided into three groups: sham-operated; coronary artery ligation; and coronary artery ligation plus administration of Guanxin No.2 decoction (10.0 g raw materials/kg per day by gavage). The experiment was carried out on day seven after ligation.

Key findings
We found that the gene expression using microarray technology showed many differences in the border infarcted left ventricular area compared with the remote noninfarcted left ventricular area after administration of Guanxin No.2 decoction.

Conclusions
Guanxin No.2 decoction has a long history in treating ischaemic cardiomyopathy in China, but the molecular mechanism has been unclear. In this study we found that some important genes may have contributed to the cardioprotective effect of Guanxin No.2 decoction.