bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigation of the ability of elemene to pass through the blood-brain barrier and its effect on brain carcinomas
Authors: Wu Xue Shen , Xie Tian , Lin Jing , Fan Hai Zhu , Huang-Fu Hong Jiao , Ni Li Feng , Yan Hui Fang 
Published: October 2010

Abstract

Objectives
Elemene is a chemical extracted from plants. It has demonstrated anti-tumour capability. Although widely studied, there has been little reported regarding its tissue distribution. Our aim was to rectify this.

Methods
The tissue distribution of elemene was studied after intragastric or intravenous administration in rats. The effectiveness of elemene in treating brain tumours was studied using the G-422 tumour cell model in mice.

Key findings
Elemene had a higher concentration in the lungs, spleen and livers than other tissues of normal rats after intragastric and intravenous administration, while the concentration in the gastrointestinal tract was greater after intragastric administration. Elemene molecules were also detected in the rats' brain tissue. Elemene had a therapeutic effect on mice inoculated with G-422 cells both intracranially and subcutaneously. The best life-extending rate and the best tumour-inhibiting rate of elemene were 64.43% and 34.46%, respectively, when 80 mg/kg elemene was used for treatment.

Conclusions
The results from the tissue distribution study showed that elemene can pass through the blood-brain barrier. The therapeutic experiments showed that elemene is effective in treating cerebral malignancy.
Effect of chronic treatment of carvedilol on oxidative stress in an intracerebroventricular streptozotocin induced model of dementia in rats
Authors: Kumar Prakash Atish , Kumar Anil 
Published: October 2010

AbstractObjectivesOxidative stress is emerging as an important issue in the pathogenesis of dementia. This study was conducted to investigate the possible neuroprotective effects of carvedilol against streptozotocin induced behavioural alterations and oxidative damage in rats.MethodsAn intracerbroventricular cannula was implanted in the lateral ventricles of male Wistar rats. Various behavioural (locomotor activity, Morris water maze task) and biochemical parameters (lipid peroxidation, nitrate concentration, catalase, acetylcholinesterase, reduced glutathione and protein) were assessed.Key findingsIntracerebroventricular administration of streptozotocin caused a significant memory deficit as evaluated in the Morris water maze task paradigms, and caused marked oxidative damage as indicated by significant increases in malondialdehyde and nitrite levels, and depletion of superoxide dismutase, catalase and reduced glutathione levels. It also caused a significant increase in acetylcholinesterase activity. Chronic administration of carvedilol (1 and 2 mg/kg, i.p.) for a period of 25 days starting 4 days before streptozotocin administration resulted in an improvement in memory retention, and attenuation of oxidative damage and acetylcholinesterase activity.ConclusionsThis study demonstrates the effectiveness of carvedilol in preventing cognitive deficits as well as the oxidative stress caused by intracerbroventicular administration of streptozotocin in rats. Carvedilol may have potential in the treatment of neurodegenerative diseases.
Ketorolac trometamol topical formulations: release behaviour, physical characterization, skin permeation, efficacy and gastric safety
Authors: El-Setouhy Doaa Ahmed , Ahmed El-Ashmony Sahar Mohy 
Published: October 2010

AbstractObjectivesThe objective of this study was to improve systemic delivery of the highly analgesic ketorolac trometamol (ketorolac tromethamine) via the transdermal route, through cost-effective topical formulations, to avoid most of the problems associated with ketorolac trometamol therapy.MethodsIn-vitro release behaviour of the drug from different microemulsion and emulgel formulations was evaluated. E2 emulgel (based on isopropyl myristate as penetration enhancer) and E7 emulgel (based on Brij 92 as penetration enhancer) were evaluated for their physical properties, rat skin permeation, in-vivo analgesic effect (hot-plate test and the paw pressure test), acute and chronic anti-inflammatory activity and gastric safety.Key findingsIsopropyl myristate and the synergistic effect of the two known penetration enhancers (propylene glycol and Brij 92) significantly modulated drug permeation and may be a promising approach for the transdermal delivery of ketorolac trometamol and other drugs. Selected in-vivo tested formulae (E2 and E7) caused significantly less ulcer score and less gastric erosion compared with oral ketorolac trometamol. E7 showed significantly higher analgesic and anti-inflammatory activity compared with E2 with no significant difference compared with oral ketorolac trometamol.ConclusionsThe developed ketorolac trometamol E7 emulgel appeared promising for dermal and transdermal delivery of ketorolac trometamol, which would circumvent most of the problems associated with drug therapy.
A bioassay for mosquito repellency against Aedes aegypti: method validation and bioactivities of DEET analogues
Authors: Jahn Alexander , Kim Seok Yong , Choi Joon-Ho , Kim Dae-Duk , Ahn Young-Joon , Yong Chul Soon , Kim Jung Sun 
Published: October 2010

Abstract

Objectives
Vector-borne diseases are still a major mortality factor in Africa and South-east Asia and effective mosquito repellents are therefore needed. An efficient and safe in-vitro assay system using artificial blood and skin substitute could facilitate the development of novel repellents, as most assays currently rely on human subjects or vertebrate whole blood. Moreover, examining the skin permeation profiles could provide safer mosquito repellents. The new assay system could serve as an initial system for testing new repellent candidates upon validation with DEET and its analogues.

Methods
N,N-Diethyl-meta-toluamide (DEET) and five analogues were synthesised and used to validate a novel in-vitro bioassay using artificial blood and collagen membrane. Repellency against Aedes aegypti was correlated with lipophilicity and skin permeation.

Key findings
The new in-vitro assay showed good reproducibility (interday relative standard deviation &lt;10% at high concentrations). Four of the five DEET analogues showed repellency similar or superior to that of DEET. Repellency correlated linearly with lipophilicity but stronger repellents tended to permeate skin better.

Conclusions
The new in-vitro assay using blood substitute and collagen membrane significantly simplifies screening of possible mosquito repellents. Lipophilicity as well as skin permeation profiles should be considered before testing of compounds that are candidates for mosquito repellents.
Enhanced oral bioavailability of etodolac by self-emulsifying systems: in-vitro and in-vivo evaluation
Authors: Barakat Nahla S 
Published: October 2010

AbstractObjectivesThe objective of this study was to prepare a self-emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion.MethodsAn optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti-inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg).Key findingsThe peak plasma concentration of 16.4 ± 1.1 μg/ml appeared after 1.3 ± 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 ± 0.5 and 10.6 ± 0.7 μg/ml at 4.2 ± 0.4 and 2.4 ± 0.2 h, respectively. The AUC0–8 of the etodolac SEDDS formulation was 2.3 times that of the pure drug and 1.4 times that of the suspension form. SEDDS formulation exhibits a 21% increase in paw thickness compared with a 39% increase on oral administration of etodolac suspension after 4 h at the same dose of the drug (20 mg/kg).ConclusionsThe result indicates the utility of SEDDS for the oral delivery of etodolac and potentially other lipophilic drugs.
Sphingosylphosphorylcholine inhibits melanin synthesis via pertussis toxin-sensitive MITF degradation
Authors: Kim Dong-Seok , Park Seo-Hyoung , Kwon Sun-Bang , Kwon Nyoun Soo , Park Kyoung-Chan 
Published: October 2010

Abstract

Objectives
Sphingolipids act as structural components in cell membranes, and form lipid intermediates that have functional roles as signalling molecules in various cellular processes. Our previous findings have suggested that sphingolipid metabolites are deeply involved in the regulation of melanogenic processes. In this study we aimed to examine sphingosylphosphorylcholine-mediated signalling pathways related to melanogenesis.

Methods
We determined the hypopigmenting effects and the related signalling pathways of sphingosylphosphorylcholine in Mel-Ab cells. In particular, we analysed the involvement of the G-protein-coupled receptor in sphingosylphosphorylcholine-induced MITF degradation.

Key findings
Western blotting revealed that sphingosylphosphorylcholine induced the activation of extracellular signal-regulated kinase (ERK), as well as Akt. Moreover, the specific Akt pathway inhibitor LY294002 blocked the hypopigmenting effect of sphingosylphosphorylcholine and abrogated the sphingosylphosphorylcholine-mediated down-regulation of microphthalmia-associated transcription factor (MITF), showing that the Akt pathway is involved in sphingosylphosphorylcholine-mediated melanin inhibition. Treatment with the proteasome inhibitor MG132 blocked the decrease in MITF by sphingosylphosphorylcholine, but sphingosylphosphorylcholine did not decrease the level of MITF mRNA, indicating that the reduction in the level of MITF results from MITF degradation. Furthermore, pre-incubation of Mel-Ab cells with pertussis toxin completely abolished the hypopigmenting effects and the activation of ERK and Akt by sphingosylphosphorylcholine, suggesting that the effects of sphingosylphosphorylcholine are mainly dependent on the G-protein-coupled receptor).

Conclusions
Together, these results suggest that sphingosylphosphorylcholine reduces melanin synthesis via pertussis toxin-sensitive ERK and Akt activation, and subsequent MITF degradation.
The involvement of endoplasmic reticulum stress in flavonoid-induced protection on cardiac cell death caused by ischaemia/reperfusion
Authors: Kim Do-Sung , Kwon Dae-Young , Kim Myung-Sunny , Kim Hye Kyung , Lee Yong Chul , Park Seong Ju , Yoo Wan Hee , Chae Soo-Wan , Chung Myoung-Ja , Kim Hyung-Ryong , Chae Han-Jung 
Published: October 2010

Abstract

Objectives
We have investigated whether endoplasmic reticulum stress and Bcl-2 proteins were linked to the protective effect exerted by flavonoids on ischaemia/reperfusion-induced cardiac damage.

Methods
Cell viability and immunoblotting were performed.

Key findings
H9c2 cardiac muscle cells were exposed to flavonoids such as biochanin A, daidzein, genistein, luteolin, quercetin and rutin, followed by ischaemia 12 h/reperfusion 4 h. The flavonoids protected against cell death induced by ischaemia/reperfusion. Flavonoid treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased that of the proapoptotic protein, Bax. The flavonoids down-regulated the expression levels of endoplasmic reticulum stress proteins, glucose-regulated protein-78, activating transcription factor 6α, X-box binding protein 1, inositol-requiring protein-1, phosphor-eukaryotic initiation factor 2α, and C/EBP-homologous protein.

Conclusions
This study suggested that the protective mechanisms of flavonoids included regulation of Bcl-2/Bax proteins as well as the endoplasmic reticulum stress proteins.
Cardiovascular effects induced by Cymbopogon winterianus essential oil in rats: involvement of calcium channels and vagal pathway
Authors: De Menezes Igor Alexandre Côrtes , Moreira Ítalo José Alves , De Paula José Welton Azevedo , Blank Arie Fitzgerald , Antoniolli Angelo Roberto , Quintans-Júnior Lucindo José , Santos Márcio Roberto Viana 
Published: October 2010

Abstract

Objectives
This study has investigated the cardiovascular effects of the Cymbopogon winterianus essential oil (EOCW) in rats. C. winterianus is a plant used in folk medicine for the treatment of hypertension.

Methods
For the measurement of haemodynamic and ECG parameters, male Wistar rats under anaesthesia were cannulated in the abdominal aorta and lower vena cava and electrodes were subcutaneously implanted in their paws. For an in-vitro approach, the rats were killed and the superior mesenteric artery was removed and cut into rings (1–2 mm). These rings were then mounted in organ baths containing Tyrode's solution at 37 °C and gassed with carbogen.

Key findings
In rats, EOCW (1–20 mg/kg, i.v.) induced dose-dependent hypotension and tachycardia. These effects were not affected by L-NAME or indometacin, but were partially reduced after atropine administration. EOCW (20 mg/kg only) also induced bradycardia-associated sinoatrial blockade, junctional rhythm, and first-degree atrioventricular block, which was abolished after atropine administration or vagotomy. In arterial rings, EOCW (0.1–3000 μg/ml) induced relaxation of phenylephrine tonus that was not affected by removal of the endothelium. These relaxations were similar to those observed in rings without endothelium precontracted with KCl 80 mm. EOCW was able to antagonize the CaCl2 (30–300 μm) induced contractions in depolarizing solution (KCl 60 mm).

Conclusions
These results demonstrated that EOCW induced hypotension and vasorelaxation. These effects appeared to be mainly mediated by Ca+2-channel blocking. Furthermore, the higher dose of EOCW induced transient bradycardia and arrhythmias due to a cardiac muscarinic activation secondary to a vagal discharge.
Potential protective effects of a traditional Chinese herb, Litsea coreana Levl., on liver fibrosis in rats
Authors: Huang Cheng , Ma Taotao , Meng Xiaoming , Lv Xiongwen , Zhang Lei , Wang Jianqing , Li Jun 
Published: October 2010

Abstract

Objectives
It was found that total flavonoids from Litsea coreana Levl. (TFLC), which is a traditional Chinese medicine, had a preventive effect against hepatic steatosis in our previous study. This study was designed to evaluate whether TFLC could improve liver fibrosis in rats.

Methods
The liver fibrosis model rats were treated with composite factors of high-fat emulsion (10 ml/kg) via gavage accompanied by a subcutaneous injection of low-dose CCl4. Thirty rats were given composite factors plus TFLC (100, 200, 400 mg/kg), respectively, for 8 weeks.

Key findings
The results showed that TFLC (200 and 400 mg/kg) treatment significantly reduced the elevation of liver index (liver weight/body weight) and spleen index (spleen weight/body weight), alanine transaminase, aspartate aminotransferase, hyaluronic acid, laminin, procollagen III N-terminal peptide, procollagenase IV and hydroxyproline. In addition, TFLC treatment improved the morphologic changes of hepatic fibrosis, suppressed expression of α-smooth muscle actin, collagen I, transforming growth factor (TGF)-β1 and TGFβ receptor (TGFβR)1, and increased peroxisome proliferator-activated receptor-γ expression in the liver of hepatic fibrosis rats.

Conclusions
In conclusion, TFLC is able to ameliorate liver injury and protect rats from liver fibrosis. This process may be related to inhibiting the expression of transforming growth factor-β1 and increasing the expression of peroxisome proliferator-activated receptor-γ.
In-vitro free radical scavenging, antiproliferative and anti-zearalenone cytotoxic effects of 4-(methylthio)-3-butenyl isothiocyanate from TunisianRaphanus sativus
Authors: Salah-Abbès Jalila Ben , Abbès Samir , Abdel-Wahhab Mosaad A , Oueslati Ridha 
Published: October 2010

AbstractObjectivesThe aim of this study was to investigate the antiradical and antioxidant properties of 4-(methylthio)-3-butenyl isothiocyanate (MTBITC) extracted from Raphanus sativus and to assess the effects of MTBITC on tumour cell growth, cytotoxicity induced by zearalenone, an oestrogenic mycotoxin, and modulation of the expression of the genes involved in these aspects of cell behaviour.MethodsA murine leukaemia cell line (L1210) was grown in vitro and supplemented with MTBITC (2, 4, 8, 16 and 32 μm) for 48 h. Cell growth was evaluated by the MTT assay. The chemopreventive role of MTBITC on the cytotoxic effect of zearalenone in a Balb/c mice keratinocyte cell line (C5-O) was also evaluated. Apoptosis and lipid peroxidation were assessed, as well as the expression of genes involved following zearalenone treatment alone or in combination with MTBITC.Key findingsMTBITC showed a significant ability to inhibit nitroblue tetrazolium reduction by superoxide radicals in a non-enzymatic superoxide generating system, to scavenge free radicals and to cause a decrease in L1210 cell growth. The C5-O cells treated with zearalenone alone showed a high frequency of apoptotic cells and lipid peroxidation, typical of oxidative stress generated by zearalenone. The cotreatment with MTBITC reduced the cytotoxicity of zearalenone and the subsequent gene expression analysis demonstrated that MTBITC decreased the expression of caspase 8, implicated in the physiological mechanism to eliminate injured or abnormal cells.ConclusionsThe results suggest that MTBITC was able to inhibit L1210 cell growth and counteract the zearalenone oxidative stress to C5-O cells through caspase 8 inhibition of apoptosis.
Nonlinear mixed effects models applied to cumulative concentration–response curves
Authors: Thorin Chantal , Mallem Mohamed Yassine , Noireaud Jacques , Gogny Marc , Desfontis Jean-Claude 
Published: October 2010

Abstract

Objectives
In experimental pharmacology, drug effect studies currently establish and analyse cumulative concentration–response curves (CCRC) under repeated measurements designs. Usually the CCRC parameters are estimated using the Hill's function in a nonlinear regression for independent data. The two-way analysis of variance is generally used to identify a statistical difference between the responses for two treatments but that analysis does not take into account the nonlinearity of the model and the heteroscedasticity (uneven distribution) of the data. We presently tested the possibility of finding a statistical solution for the nonlinear response in repeated measurements data using the nonlinear mixed effects (nlme) models.

Methods
Experimental data sets, originating from studies on β-adrenoceptor-induced relaxation in rat thoracic aorta ring, were analysed using the nlme methods.

Key findings
Comparison with classical methods showed the superiority of the nlme models approach. For each pharmacological parameter (Em, n, pD2), a point estimate, a standard error and a confidence interval are returned by the nlme procedures respecting the assumption of independency and normality of the residuals.

Conclusions
Using the method presently described, it is now possible to detect significant differences for each pharmacological parameter estimated in different situations, even for designs with small samples size (i.e. at least six complete curves).
Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart
Authors: Kolettis Theofilos M , Kontaras Konstantinos , Spartinos Ioannis , Maniotis Christos , Varnavas Varnavas , Koutouzis Michael , Mourouzis Iordanis , Papalois Apostolos , Pantos Constantinos , Kyriakides Zenon S 
Published: October 2010

Abstract

Objectives
Sildenafil may be beneficial during myocardial ischaemia/reperfusion, but this effect may be dose-dependent, accounting for previous conflicting results. We have explored the effects of two acute and one chronic administration regimen on left ventricular function.

Methods
The study was conducted on 36 Wistar rats (290 ± 7 g). Sildenafil was administered 30 min before ischaemia at a low (0.7 mg/kg, n= 8) or high (1.4 mg/kg, n= 8)dosage. The chronic treatment arm (n= 8) consisted of two daily injections of sildenafil (0.7 mg/kg) for three weeks. The control group was formed by 12 rats. Ischaemic contracture, post-ischaemic recovery and hypercontracture were measured in isolated, Langendorff-perfused preparations.

Key findings
Ischaemic contracture tended to be lower after high-dose sildenafil, while remaining unchanged after low-dose or chronic sildenafil administration. Compared with controls (62.9 ± 2.0% of baseline developed pressure), post-ischaemic recovery was higher (P= 0.0069) after low dose (75.1 ± 2.4%), unchanged (P= 0.13) after high dose (69.1 ± 2.1%), but lower (P &lt; 0.001) after chronic (42.9 ± 4.5%) sildenafil administration. Compared with controls (71.8 ± 3.9 mmHg), hypercontracture was higher (P= 0.0052) after chronic sildenafil administration (89.5 ± 4.1 mmHg), but similar after acute low dose (65.7 ± 3.3 mmHg, P= 0.33) or high dose (67.1 ± 4.7 mmHg, P= 0.43).

Conclusions
The effects of sildenafil after ischaemia/reperfusion were strongly dose-dependent. Beneficial actions on left ventricular function were evident after acute pretreatment with a low dosage, but were lost after doubling the dose. Chronic sildenafil administration deteriorated left ventricular function during ischaemia and reperfusion.
Effects of morroniside isolated from Corni Fructus on renal lipids and inflammation in type 2 diabetic mice
Authors: Park Chan Hum , Noh Jeong Sook , Tanaka Takashi , Yokozawa Takako 
Published: October 2010

Abstract

Objectives
The effects of morroniside isolated from Corni Fructus on renal lipids and inflammation provoked by hyperglycaemia were investigated using type 2 diabetic mice.

Methods
Morroniside was administered orally to db/db mice at 20 or 100 mg/kg daily for 8 weeks, and its effects were compared with those in vehicle-treated db/db and m/m (non-diabetic) mice. Serum and renal biochemical factors and protein expression related to lipid homeostasis and inflammation were measured.

Key findings
Morroniside produced significant dose-dependent reductions in serum triglyceride and renal glucose and lipid levels. Morroniside altered the abnormal protein expression of sterol regulatory element binding proteins (SREBP-1 and SREBP-2). In addition, the formation of reactive oxygen species and lipid peroxidation were inhibited in the morroniside-treated db/db mouse group, and the ratio of reduced glutathione to the oxidised form was significantly elevated. These results suggest that morroniside alleviated oxidative stress in the kidneys of db/db mice. Furthermore, 100 mg/kg morroniside down-regulated the expression of nuclear factor-κBp65, cyclooxygenase-2 and inducible nitric oxide synthase augmented in db/db mice.

Conclusions
Morroniside may inhibit abnormal lipid metabolism and inflammation due to reactive oxygen species in the kidneys in type 2 diabetes.