bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of a novel symmetrical shape factor to gastroretentive matrices as a measure of swelling synchronization and its impact on drug release kinetics under standard and modified dissolution conditions
Authors: Liu Quan , Fassihi Reza 
Published: October 2010

Abstract

Objectives
We have assessed the kinetics of drug release in relation to the full or partial hydration and swelling of matrices under standard and modified United States Pharmacopeia (USP) apparatus II using a novel index, defined as the symmetrical shape factor. The symmetrical shape factor describes the regularity of the hydration rate of the matrix perimeter relative to its central regions.

Methods
Monolithic and three-layer matrices based on hypromellose, polyethylene oxide, Kollidon SR, theophylline, diltiazem hydrochloride and alfuzosin hydrochloride were subjected to dissolution testing.

Key findings
Our results indicated that Kollidon SR matrices and the three-layer composite systems with and without effervescing components were not significantly affected by the dissolution conditions. However, in the case of the floating monolithic systems based on hypromellose and polyethylene oxide, both release profiles and swelling dynamics in accordance with the similarity factor (f2) and symmetrical shape factor values were significantly influenced.

Conclusions
The symmetrical shape factor values were positively impacted. Consequently the drug release kinetics were more predictable and reproducible. The modified USP method resulted in a more synchronized axial and radial swelling with symmetrical shape factor values approaching unity. Data further indicated that the modified USP method provided for complete matrix hydration and swelling as the dosage form remained fully submerged, allowing for more reliable release mimicking the in-vivo conditions.
An improved primary human nasal cell culture for the simultaneous determination of transepithelial transport and ciliary beat frequency
Authors: Mallants Roel , Vlaeminck Valerie , Jorissen Mark , Augustijns Patrick 
Published: October 2010

Abstract

Objectives
The aim was to establish a preclinical in-vitro system of the nasal mucosa for the simultaneous evaluation of nasal absorption and effects on ciliary activity.

Methods
Human nasal epithelial cells were grown in collagen-coated transport inserts with transparent polyethylene terephthalate membranes (3 μm). Transepithelial transport and ciliary beat frequency values were measured every 15 min for 1 h.

Key findings
The apparent permeability coefficients (Papp) for atenolol (mainly paracellular transport) and propranolol (transcellular transport) amounted to 0.1 ± 0.1 and 23.7 ± 0.6 × 10−6 cm/s, respectively, illustrating that the system can be used to discriminate between high permeability and low permeability compounds. Transport of talinolol (substrate for the P-glycoprotein efflux carrier) did not reveal polarity (0.3 ± 0.2 and 0.2 ± 0.1 × 10−6 cm/s for absorptive and secretory transport, respectively) and was not affected by verapamil (10 μm), suggesting the absence of P-glycoprotein in the nasal cell culture. No significant effects of atenolol, propranolol and talinolol on ciliary beat frequency were observed (98 ± 20% of the control condition after 60 min). Chlorocresol significantly decreased the ciliary activity but this decrease was not accompanied by effects on the transepithelial transport of atenolol, propranolol and talinolol.

Conclusions
A new system was developed which offers possibilities as a fast screening tool for studying the potential of compounds for nasal drug administration, since permeability and a possible cilio-toxic effect can be assessed simultaneously.
Site-specific contribution of proton-coupled folate transporter/haem carrier protein 1 in the intestinal absorption of methotrexate in rats
Authors: Yokooji Tomoharu , Mori Nobuhiro , Murakami Teruo 
Published: October 2010

AbstractObjectivesMethotrexate is reportedly a substrate for proton-coupled folate transporter/haem carrier protein 1 (PCFT/HCP1) and reduced folate carrier 1 (RFC1). In this study, we examined the contribution of PCFT/HCP1 and RFC1 in the intestinal absorption of methotrexate in rats.MethodsWestern blot analysis was carried out to evaluate the protein levels of PCFT/HCP1 and multidrug resistance-associated protein 2 in brush-border membrane of rat small intestine. Mucosal uptake of methotrexate was studied in the rat everted small intestine and an in-situ intestinal perfusion study of methotrexate was also carried out in rats.Key findingsIn transport studies using everted intestine, the mucosal methotrexate influx rate in proximal intestine at pH 5.5 was significantly greater than that at pH 7.4. Coadministration of folate or its analogues, such as folinate and 5-methyltetrahydrofolate, substrates for both PCFT/HCP1 and RFC1, significantly suppressed the methotrexate influx at pH 5.5, whereas thiamine pyrophosphate, an inhibitor for RFC1 alone, exerted no significant effect. Western blot analysis showed higher PCFT/HCP1 expression in proximal than distal small intestine. In distal small intestine, methotrexate influx rate was low and was not pH dependent. Also, folate and its analogues exerted no significant effect on methotrexate absorption.ConclusionsBased on the present and our previous results, the site-specific contributions of various transporters including PCFT/HCP1 in methotrexate intestinal absorption were discussed. The variation in luminal pH and the involvement of multiple transporters in methotrexate absorption may cause variation in oral bioavailability among patients.
Monoketocholate can decrease transcellular permeation of methotrexate across Caco-2 cell monolayers and reduce its intestinal absorption in rat
Authors: Chen Gong , Fawcett J Paul , Mikov Momir , Tucker Ian G 
Published: October 2010

AbstractObjectivesBile salts have been shown to decrease the absorption of methotrexate in the rat intestine by an unknown mechanism. We aimed to examine this effect.MethodsWe assessed apical-to-basolateral (AP-BL) permeation of methotrexate (5 μM) across Caco-2 cell monolayers pretreated with various concentrations (0, 0.25, 0.5, 1, 3 and 5 mm) of sodium cholate or its semisynthetic analogue, sodium 12-monoketocholate. We also determined the effect of orally administered 12-monoketocholate on the intestinal absorption of methotrexate in rats to evaluate a possible in-vitro–in-vivo correlation.Key findingsIt was found that sodium cholate and sodium 12-monoketocholate decreased the AP-BL permeation of methotrexate at low concentrations (maximal inhibition at 0.25 and 1 mm, respectively) and increased it at higher concentrations. Determination of [14C] mannitol permeation and electrical resistance of monolayers during experiments showed that membrane integrity was not compromised at low concentrations of bile salts but was disrupted at higher concentrations. Subsequently, we examined the effect of the simultaneous oral administration of sodium 12-monoketocholate (4, 20, 40 and 80 mg/kg) on the intestinal absorption of methotrexate in rats after an oral dose (5 mg/kg). The pharmacokinetic study showed that 12-monoketocholate at 4 and 20 mg/kg did not change the methotrexate area under the serum concentration–time curve whereas sodium 12-monoketocholate at 40 and 80 mg/kg significantly reduced it.ConclusionsSodium 12-monoketocholate appears to decrease the intestinal absorption of methotrexate in rats by inhibition of transcellular active transport.
Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver
Authors: Turkanovic Jasmina , Ngo Suong N T , Milne Robert W 
Published: October 2010

Abstract

Objectives
This study examined the effects of St John's wort (Hypericum perforatum) on the disposition of fexofenadine, a substrate of P-glycoprotein/organic anion transporting polypeptide, in the isolated perfused rat liver.

Methods
Male Sprague-Dawley rats were given St John's wort, 1000 mg/kg, by intragastric gavage once daily for 14 days. On day 15, livers were isolated surgically and perfused in a recirculating system with fexofenadine (2 μg/ml), either alone or following addition of ciclosporin (0.5 μg/ml) 5 min before the addition of fexofenadine. Perfusate samples and bile were collected for 60 min. Fexofenadine in perfusate, bile and the homogenised livers was measured by HPLC.

Key findings
Administration of St John's wort significantly increased biliary clearance with respect to perfusate and biliary clearance with respect to the concentration in the liver, by 74% and 71%, respectively. This was reversed by ciclosporin.

Conclusions
St John's wort enhanced the elimination of fexofenadine into the bile. This could be because it increases the activity of P-glycoprotein on the canalicular membrane of hepatocytes.
Anti-inflammatory effects of Artemisia princeps in antigen-stimulated T cells and regulatory T cells
Authors: HoChang Sung , Jung Eun Jung , Park Youn Hee , Lim Dong Gyun , Ko Na Young , Choi Wahn Soo , Her Erk , Kim Soo Hyun , Choi Kang Duk , Bae Jae Ho , Kim Sun Hee , Kang Chi Dug , Han Duck Jong , Kim Song Cheol 
Published: October 2010

Abstract

Objectives
The aim was to investigate the anti-inflammatory effects of Artemisia princeps extract on the activity of anti-CD3/CD28-stimulated CD4+CD25- T cells and antigen-expanded regulatory T cells.

Methods
CD4+CD25- T cells were activated with coated anti-CD3 and anti-CD28 and cultured in the presence or absence of various concentrations of A. princeps extract. The cultures were pulsed on Day 6 with [3H]thymidine and, after harvesting the cells, [3H] thymidine incorporation was measured. For analysis of interleukin-2 and interferon-γ secreted from CD4+CD25- T cells, culture supernatants were collected on Days 2 and 6. For the analysis of interleukin-10 secreted from the CD4+CD25- T cells and expanded regulatory T cells, supernatants were collected after 2 and 7 days, respectively. Cytokine levels were determined using an enzyme-linked immunosorbent assay. Potential medicinal components of the A. princeps extract were determined using gas chromatography–mass spectrometry.

Key findings
A. princeps (30 μg/ml) effectively suppressed proliferation of CD4+CD25- T cells that were stimulated with anti-CD3/CD28 without causing cytotoxicity in spleen cells incubated under conditions lacking antigen stimulation. A. princeps inhibited production of the pro-inflammatory cytokines interleukin-2 and interferon-γ in anti-CD3/CD28-stimulated CD4+CD25- T cells. Also, the extract slightly increased production of the anti-inflammatory cytokine interleukin-10 in these cells. In regulatory T cells expanded by anti-CD3/CD28, A. princeps increased production of interleukin-10 and Foxp3.

Conclusions
The results suggest that A. princeps may be useful in the treatment of autoimmune diseases and organ transplantation rejection by inhibiting proliferation of inflammatory T cells, suppressing inflammatory processes in antigen-stimulated CD4+CD25- T cells and increasing activity of expanded regulatory T cells.
A novel compound from celery seed with a bactericidal effect against Helicobacter pylori
Authors: Zhou Yong , Taylor Brian , Smith Thomas J , Liu Zhong-ping , Clench Malcolm , Davies Noel W , Rainsford K D 
Published: October 2010

Abstract

Objectives
The aim was to purify and characterise an antimicrobial component from celery (Apium graveolens) seeds, which have been used for centuries as a herbal medicine with reported antibacterial effects.

Methods
A crude alcoholic extract of celery seeds was fractionated by organic solvent extractions, column chromatography and HPLC. Fractions were assayed for antimicrobial activity against the gastric pathogen Helicobacter pylori and other bacteria. The purified antibacterial component was characterised via MS and NMR. Preliminary investigation of its mechanism of action included morphological studies, incorporation of macromolecular precursors, membrane integrity and two-dimensional protein electrophoresis.

Key findings
The purified component, termed ‘compound with anti-Helicobacter activity’ (CAH), had potent bactericidal effects against H. pylori; the minimum inhibitory concentration and minimum bactericidal concentration were 3.15 μg/ml and 6.25–12.5 μg/ml, respectively. CAH (Mr = 384.23; empirical formula C24H32O4) had specific inhibitory effects on H. pylori and was not active against Campylobacter jejuni or Escherichia coli. MS and NMR data were consistent with a dimeric phthalide structure. The results appeared to rule out mechanisms that operated solely by loss of membrane integrity or inhibition of protein or nucleic acid synthesis.

Conclusions
CAH may be suitable for further investigation as a potent agent for treating H. pylori infections.
Anti-inflammatory activity and possible mechanism of extract from Mikania laevigata in carrageenan-induced peritonitis
Authors: Alves Claudiney F , Alves Vanessa B F , de Assis Izabel P , Clemente-Napimoga Juliana T , Uber-Bucek Elizabeth , Dal-Secco Daniela , Cunha Fernando Q , Rehder Vera L G , Napimoga Marcelo H 
Published: October 2010

Abstract

Objectives
The aim was to test the potential use of an extract of Mikania laevigata (popularly known in Brazil as guaco), made from leaves harvested in different months of the year, on neutrophil migration after an inflammatory stimulus and investigate the underlying molecular mechanisms.

Methods
We examined the effect of guaco on vascular permeability and leucocyte function in carrageenan-induced peritonitis in mice.

Key findings
Our results demonstrated that guaco extract administered subcutaneously (3 mg/kg) decreased the vascular permeability and also leucocyte rolling and adhesion to the inflamed tissues by a mechanism dependent on nitric oxide. Specifically, inhibitors of nitric oxide synthase remarkably abrogated the guaco extract-mediated suppression of neutrophil migration to the inflammatory site. In addition, guaco extract-mediated suppression of neutrophil migration appeared to be dependent on the production of the cytokines interleukin-1β and tumour necrosis factor-α. One of the major constituents of the guaco extract, coumarin, was able to inhibit the neutrophil migration towards the inflammatory focus.

Conclusions
In conclusion the anti-inflammatory effect induced by guaco extract may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.
Characterisation of a novel conjugate of ibuprofen with 3-hydroxybutyric acid oligomers
Authors: Stasiak Pawel , Ehrhardt Carsten , Juzwa Maria , Sznitowska Malgorzata 
Published: October 2010

Abstract

Objectives
A conjugate of ibuprofen with 3-hydroxybutyric acid oligomers has been evaluated as a novel drug delivery model system.

Methods
This paper focuses on the synthesis and the characterisation of the physicochemical properties of this conjugate, and on hydrolysis studies in aqueous buffers and simulated intestinal fluid. We also describe the development of an analytical method (HPLC) for hydrolysis studies of this compound.

Key findings
The conjugate had high stability in aqueous solutions of pH 6–8 and underwent slow enzymatic hydrolysis.

Conclusions
This conjugate is not well suited for oral administration but might be considered a candidate for development of prodrug preparations for parenteral or topical sustained release.
Altered expression of MRP2, MRP3 and UGT2B1 in the liver affects the disposition of morphine and its glucuronide conjugate in a rat model of cholestasis
Authors: Hasegawa Yoshitaka , Kishimoto Shuichi , Takahashi Hirokazu , Inotsume Nobuo , Takeuchi Yoshikazu , Fukushima Shoji 
Published: October 2010

Abstract

Objectives
The aim was to investigate the disposition of morphine and morphine-3-glucuronide (M3G) in a rat model of cholestasis induced by bile duct ligation (BDL).

Methods
Morphine (15 mg/kg) was administered intravenously, and morphine and M3G concentrations in the plasma and urine measured by HPLC. Changes in the mRNA expression of multidrug resistance-associated protein (MRP)2, MRP3 and UDP-glucuronosyltransferase (UGT)2B1 in the liver were estimated using RT-PCR.

Key findings
Although the plasma morphine concentrations declined exponentially, the elimination was delayed 3 and 5 days after BDL. Plasma M3G concentrations on day 1 after BDL were similar to those in the untreated control group, but were increased 3 and 5 days after BDL. Expression of MRP3 and UGT2B1 mRNA increased after BDL. The urinary excretion of M3G was increased significantly after BDL.

Conclusions
Enhanced glucuronidation of morphine and transportation of M3G into the blood increased the plasma M3G concentration in the BDL groups. However, M3G disposition 1 day after BDL was similar to that in the untreated control group because urinary excretion of M3G increased.
Enhancement of amlodipine cardioprotection by quercetin in ischaemia/reperfusion injury in rats
Authors: Ahmed Lamiaa A , Salem Hesham A , Attia Amina S , El-Sayed Mostafa E 
Published: October 2010

Abstract

Objectives
To investigate the possible modification of the cardioprotective effect of amlodipine when co-administered with quercetin in myocardial ischaemia/reperfusion-induced functional, metabolic and cellular alterations in rats.

Methods
Oral doses of amlodipine (15 mg/kg) and quercetin (5 mg/kg), alone or in combination, were administered once daily for 1 week. Rats were then subjected to myocardial ischaemia/reperfusion (35min/10min). Heart rates and ventricular arrhythmias were recorded during ischaemia/reperfusion progress. At the end of reperfusion, activities of plasma creatine kinase (CK) and cardiac myeloperoxidase were determined. In addition, cardiac contents of lactate, ATP, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total nitrate/nitrite (NOx) were estimated. Finally, histological examination was performed to visualize the protective cellular effects of different pretreatments.

Key findings
Combined therapy provided significant improvement in the amlodipine effect toward preserving cardiac electrophysiologic functions, ATP and GSH contents as well as reducing the elevated plasma CK, cardiac TBARS and NOx contents.

Conclusion
Quercetin could add benefits to the cardioprotective effect of amlodipine against injury induced in the heart by ischaemia/reperfusion.
Boswelliaresin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials
Authors: Moussaieff Arieh , Mechoulam Raphael 
Published: October 2010

AbstractObjectivesDespite its historical-religious, cultural and medical importance, Boswellia has not been thoroughly studied, and gaps still exist between our knowledge of the traditional uses of the resin and the scientific data available. Here we review the pharmacology of Boswellia resin and of the small molecules identified as the active ingredients of the resin.Key findingsThe resin of Boswellia species (‘frankincense’, ‘olibanum’) has been used as incense in religious and cultural ceremonies since the beginning of written history. Its medicinal properties are also widely recognized, mainly in the treatment of inflammatory conditions, as well as in some cancerous diseases, wound healing and for its antimicrobial activity. Until recently, work on Boswellia focused on the immunomodulatory properties of the resin and boswellic acids were considered to be the main, if not the only, active ingredients of the resin. Hence, this family of triterpenoids was investigated by numerous groups, both in vitro and in vivo. These compounds were shown to exert significant anti-inflammatory and pro-apoptotic activity in many assays: in vitro, in vivo and in clinical trials. We recently found incensole acetate and its derivatives, which are major components of Boswellia resin, to be nuclear factor-κB inhibitors, thus suggesting that they are, at least in part, responsible for its anti-inflammatory effects. Incensole acetate also exerts a robust neuroprotective effect after brain trauma in mice. Furthermore, it causes behavioural as well as anti-depressive and anxiolytic effects in mice. It is also a potent agonist of the transient receptor potential (TRP)V3 channel. It thus seems that incensole acetate and its derivatives play a significant role in the effects that Boswellia resin exerts on biological systems.ConclusionsAltogether, studies on Boswellia resin have provided an arsenal of bio-active small molecules with a considerable therapeutic potential that is far from being utilized.
In-vitro and in-vivo metabolic studies of the candidate chemopreventative pentamethylchromanol using liquid chromatography/tandem mass spectrometry
Authors: Gorman Gregory S , Coward Lori , Kerstner-Wood Corenna , Freeman Lea , Hebert Charles D , Kapetanovic Izet M 
Published: October 2010

AbstractObjectivesThis study focuses on the in-vitro metabolic profiles of pentamethyl-chromanol in human, rat, dog and non-human primates, and characterizes the associated metabolic kinetics and specific human isozymes responsible for metabolism. Additional investigations compare in-vitro data with in-vivo metabolic data from rats and dogs.MethodsIn-vitro metabolites were generated from commercially available microsomes, S9 fractions and cytochrome P450 isozymes. Reaction mixtures were analysed using liquid chromatography/tandem mass spectrometry for metabolite identification, stability, pheno-typing and kinetic profiles. Plasma samples were collected from 28-day toxicology studies in rats and dogs, and analysed using the same methodology as for the identification of in-vitro metabolites.Key findingsSamples from in-vitro experiments produced a total of eight identified metabolites while five were observed in the in-vivo samples. Kinetic analysis of metabolites in human microsomes generated Michaelis constants (KM) ranging from 10.9 to 104.9 μM. Pentamethylchromanol metabolic stability varied by species and multiple isozymes were identified for the observed biotransformation pathways. Pentamethylchromanol is susceptible to multiple metabolic pathways and differential metabolic stability, which is species dependent.ConclusionsIn-vitro metabolism was not a strong predictor of in-vivo metabolism for the samples assays but showed glucuronidation and sulfation as common biotransformation pathways.
Faster clearance of mirodenafil in rats with acute renal failure induced by uranyl nitrate: contribution of increased protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2
Authors: Choi Young H , Lee Young S , Kim Tae K , Lee Bong-Y , Lee Myung G 
Published: October 2010

Abstract

Objectives
It has been reported that mirodenafil is primarily metabolized via hepatic cytochrome P450 (CYP) 1A1/2, 2B1/2, 2D1 and 3A1/2 in rats. It has also been reported that the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 increases and that of hepatic CYP2D1 decreases in rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the pharmacokinetics of mirodenafil were studied in control and U-ARF rats.

Methods
The pharmacokinetic parameters of mirodenafil and SK3541 (a metabolite of mirodenafil) were compared after the intravenous and oral administration of mirodenafil at a dose of 20 mg/kg to U-ARF and control rats.

Key findings
After interavenous administration of mirodenafil to U-ARF rats, the total area under the concentration–time curve (AUC) of mirodenafil was significantly smaller (36.5% decrease) than controls, possibly due to the significantly faster non-renal clearance (66.1% increase; because of increase in the protein expression of hepatic CYP3A1) than controls. After the oral administration of mirodenafil to U-ARF rats, the AUC of mirodenafil was also significantly smaller (47.8% decrease) due to the increase in the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 compared with controls.

Conclusions
After both intravenous and oral administration of mirodenafil to U-ARF rats, the AUCSK3541/AUCmirodenafil ratios were comparable with that in controls and this could be due to further metabolism of SK3541 in rats.