bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of acute hepatic failure on the hepatic first-pass effect of 5-fluorouracil in rats
Authors: Nagata Masashi , Hidaka Yumi , Hidaka Muneaki , Kawano Yohei , Iwakiri Tomomi , Okumura Manabu , Arimori Kazuhiko 
Published: September 2015

Abstract

Objectives
In cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil is widely used and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and reduce systemic toxicity. 5-Fluorouracil is eliminated primarily by the liver and so the hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil may be lower in patients with hepatic failure, and systemic toxicity may not be reduced. In this study, we have investigated the effect of acute hepatic failure on the first-pass effect of 5-fluorouracil in rats.

Methods
Experimental acute hepatic failure was induced by treatment with carbon tetrachloride (CCl4). 5-Fluorouracil was infused for 15 min into the hepatic artery or the saphenous vein of rats at a dose of 1.25 mg/kg.

Key findings
Hepatic availability in 50% CCl4-treated (severe hepatic failure) rats was higher than in controls.

Conclusions
The hepatic first-pass effect after intrahepatic arterial administration of 5-fluorouracil was lower in severe hepatic failure. Therefore, the reducing effect of the systemic toxicity after intrahepatic arterial administration may be lower in severe hepatic failure.
Influence of etoricoxib on anticonvulsant activity of phenytoin and diazepam in experimental seizure models in mice
Authors: Jayaraman R , Manisenthil K T , Anitha T , Joshi Vishal D , Palei Narahari N , Gajera Kalpesh , Ladani Krupali 
Published: September 2015

Abstract

Objectives
Our aim was to investigate the effect of etoricoxib on the anticonvulsant activity of phenytoin and diazepam against seizure models in mice. In addition the acute adverse effect of etoricoxib was assessed with a chimney test.

Methods
The maximal seizure pattern was induced in mice by giving an alternating current of 50 mA for 0.2 s, while chemical seizures were induced by intraperitoneal injection of pentylenetetrazole at its CD97 dose (97% convulsive dose for the clonic phase). Test drug was administered 45 min before the electrical or chemical induction of seizures in combination with conventional antiepileptics. The ability of the test drug to reduce or abolish the extensor phase of maximal electroshock and clonic-type seizures in the chemical induction method was selected as anti-seizure criteria.

Key findings
Concurrent treatment with etoricoxib at an oral dose of 10 mg/kg reduced the anticonvulsant potency of phenytoin. The protective effects of diazepam against pentylenetetrazole-induced convulsions was significantly increased and the mortality rate was reduced by concurrent treatment with etoricoxib (10 mg/kg p.o.) when compared with diazepam groups. No neurotoxic effect was observed with etoricoxib (10 mg/kg p.o.) and it had no impact on motor coordination in the chimney test in mice. Etoricoxib applied at its highest dose (10 mg/kg) significantly enhanced the free plasma levels of diazepam whereas the free plasma levels of phenytoin were significantly reduced.

Conclusions
The obtained results suggest that the preferential cyclooxygenase-2 inhibitor etoricoxib significantly reduced the anticonvulsant action of phenytoin and significantly increased the beneficial action of diazepam against maximal electroshock and pentylenetetrazole-induced convulsions in a mouse model.
Uptake of nicotine from suspension culture of Nicotiana tabacum by molecularly imprinted polymers
Authors: Abdelkader Mohamed Salaheldin A , Lockwood Brian , Sansongsak Proramate 
Published: September 2015

Abstract

Objectives
The aim was to use molecularly imprinted polymers (MIPs) for the selective recovery of nicotine in plant cell cultures. MIPs can selectively uptake nicotine from suspension cultures of N. tabacum, and therefore may be useful for improving levels of secondary metabolites in plant cell cultures.

Methods
Suspension cultures of N. tabacum were initiated from callus and maintained in liquid Murashige and Skoog (MS) media containing 3% w/v sucrose, 0.1 mg/l α-naphthaleneacetic acid acid (NAA) and 0.25 mg/l kinetin. Tween 80 at 1% was used for permeabilisation of cell cultures. Pre-weighed XAD-2 and two types of synthesized polymers, MIPs (A and B with one and two functional monomers, respectively) and corresponding non-imprinted polymers (NIPs), A and B, were introduced aseptically into the permeabilised suspension cultures of N. tabacum, the nicotine contents of polymers were determined by gas chromatography and the adsorption yield of polymers were determined.

Key findings
Cell cultures of N. tabacum accumulated nicotine alkaloid intracellularly in varying levels, 6.8–14.9 mg/l fresh weight. MIPs were able to uptake 50–70% of released nicotine in suspension cultures of N. tabacum, whereas XAD-2 recovered only 30–40%. The total levels of accumulated nicotine were enhanced up to 20 mg/l by simultaneous use of Tween 80 and MIPs.

Conclusions
The findings indicate the potential use of MIPs to uptake nicotine from suspension cultures of N. tabacum, and increase productivity of secondary metabolites in plant cell cultures.
Change in tolbutamide permeability in rat jejunum and Caco-2 cells by Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine
Authors: Nishimura Nobuhiro , Uemura Tomichika , Iwamoto Kikuo , Naora Kohji 
Published: September 2015

Abstract

Objectives
This study was designed to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the membrane permeability of tolbutamide in the intestinal tract. We carried out an in-situ loop study with rat jejunum and a transport study with Caco-2 cell monolayers.

Methods
In the in-situ loop study, absorption clearance of tolbutamide was estimated from the drug concentrations in the loop and plasma. The apical-to-basolateral and basolateral-to-apical transport of tolbutamide and d-mannitol, a paracellular transport marker, was assessed using Caco-2 cell monolayers cultured on a polycarbonate membrane.

Key findings
The absorption clearance of tolbutamide was enhanced by a concomitant dose of Sho-saiko-to over 10 min in the rat in-situ loop. Sho-saiko-to increased the apical-to-basolateral transport of tolbutamide, whereas the basolateral-to-apical transport of this drug was reduced by Sho-saiko-to. On the other hand, in both directions the Papp of d-mannitol was reduced by the presence of Sho-saiko-to. Furthermore, the apical-to-basolateral transport of tolbutamide in ATP-depleted Caco-2 cells was diminished by Sho-saiko-to. These findings suggest that Sho-saiko-to can facilitate the epithelial membrane permeability of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers. Since Sho-saiko-to suppressed the passive transport of tolbutamide from the apical-to-basolateral side, enhanced permeability may be related to effects of Sho-saiko-to on the energy-dependent transport of tolbutamide in the intestine.

Conclusions
Our findings suggest that Sho-saiko-to might facilitate the energy-dependent transport of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers.
Recent advances in skin ‘barrier’ research
Authors: Rawlings Anthony V 
Published: September 2015

Abstract

Objectives
Our knowledge on the complexity of stratum corneum biology, chemistry and biophysics has grown over the last decade. This and the intricate control mechanisms in the stratum corneum that bring about its full and proper structural maturity will be reviewed.

Key findings
The importance of the total architecture of the stratum corneum in relation to desquamation and barrier function, the role of the corneodesmosomes and their degrading enzymes, new insights into the importance of natural moisturising factor and the emerging knowledge on the chemical antimicrobial barrier of the stratum corneum are discussed.

Summary
Despite our increasing knowledge of the complexity of stratum corneum, we are still far from understanding its intricate control mechanisms that bring about its maturity and desquamation.
Dynamic foams in topical drug delivery
Authors: Zhao Yanjun , Jones Stuart A , Brown Marc B 
Published: September 2015

Abstract

Objectives
Pharmaceutical foams are not new inventions and their application in topical therapy can be traced back three decades. However, foam formulations have been gaining in popularity with over 100 patents published globally in the last 10 years alone. The aim of this paper is to review the current status and explore the future potential of dynamic foam vehicles in the field of topical drug delivery.

Key findings
The use of foam technology to deliver a range of topical active agents has been claimed, including sun-screening compounds, corticosteroids, and antibacterial, antifungal and antiviral agents. Although foams present distinct application advantages and improved patient compliance, the real reason for the rapid growth of topical foam technology is that foams as elegant, aesthetic and cosmetically appealing vehicles provide an alternative, promising formulation strategy in the highly competitive dermatological market. Although there is a plethora of published data proving the safety profiles of topical foams there is a lack of sufficient clinical evidence to demonstrate any superiority of foams over other traditional topical vehicles such as creams and ointments for drug delivery.

Summary
Recent literature suggests that when foams are properly engineered using the advances of in situ analysis techniques, the enhancement of topical drug delivery via engineering this type of vehicle can be achieved.
Enhanced skin permeation and hydration by magnetic field array: preliminary in-vitro and in-vivo assessment
Authors: Benson Heather A E , Krishnan Gayathri , Edwards Jeffrey , Liew Yih Miin , Wallace Vincent P 
Published: September 2015

Abstract

Objectives
The aim of the study was determine the effect of magnetic film array technology on the skin permeation of urea.

Methods
A 5% urea gel was applied to human epidermal membrane in vitro and human skin in vivo. Application of gel with magnetic film array and plastic occlusive film was compared with application of gel with a plastic occlusive film and non-magnetic film. In-vitro epidermal penetration was determined using a Franz-type diffusion system. In-vivo permeation and changes in epidermal properties were visualised by optical coherence tomography.

Key findings
The mean cumulative permeation of urea over 2 h for magnetic film array application was 89.54 ± 7.34 μg/cm2 as compared with 20.83 ± 2.02 μg/cm2 for passive occluded application (mean ± SEM, n = 9/8), representing greater than 4-fold increase over the 2-h application time period. Administration of urea with the magnetic film array resulted in the lag time being reduced from 40.58 ± 3.98 to 21.13 ± 6.27 min (P &lt; 0.02), while steady state flux increased from 0.24 ± 0.03 to 0.75 ± 0.06 μg/cm2 per min (P &lt; 0.0001). Under active occlusion, the relative change in epidermal thickness as determined by optical coherence tomography increased by 16 and 11% at 30 and 60 min, respectively.

Conclusions
Administration with a novel magnetic film array technology provided enhanced skin penetration of urea and increased epidermal hydration when compared with administration under an occlusive film only.
Electroosmotic transport of mannitol across human nail during constant current iontophoresis
Authors: Dutet Julie , Delgado-Charro M Begoña 
Published: September 2015

Abstract

Objectives
This work aimed to elucidate the role of electroosmosis during trans-nail iontophoresis.

Methods
Passive and iontophoretic experiments were performed after short hydration (10–15 min) of human nail tips. The electroosmotic fluxes of mannitol were determined during anodal and cathodal iontophoresis and at different pH values. Passive controls were also carried out. Four sets of experiments were performed: (a) three anodal delivery experiments using different nails, at pH 4.0, 5.0 and 7.4, (b) one anodal delivery experiment that kept the same nails across two pH stages, (c) one experiment, comprising an anodal delivery stage (pH 4 and 7.4) followed by a cathodal delivery stage (pH 7.4 and 4), which kept the same nails across the different polarities and pH stages, and (d) a passive experiment keeping the same nails across different pH values (4 and 7.4).

Results
The fluxes of mannitol measured were very variable and little difference between passive and electroosmotic transport was observed. Cathodal and anodal fluxes were not always significantly different. Experiments which minimised internail variability suggested that the nails were negatively charged at physiological pH, and that this negative charge was lost at pH 4.

Conclusions
These results suggest a modest and highly variable contribution of electroosmosis to the iontophoretic transungual flux.
Effect of a novel penetration enhancer on the ungual permeation of two antifungal agents
Authors: Traynor M J , Turner R B , Evans C R G , Khengar R H , Jones S A , Brown M B 
Published: September 2015

Abstract

Objectives
The aim of this study was to demonstrate the effect of a novel permeation enhancer system using two existing marketed nail lacquers and the delivery of terbinafine through human nail samples in vitro.

Methods
Initially a modified Franz cell was used, where sections of human nail serve as the barrier through which drug penetrates into an agar-filled chamber infected with dermatophytes. A second study was performed using a novel infected nail model where dermatophytes are incubated with and grow into human nail and ATP levels are used as biological marker for antimicrobial activity.

Key findings
The novel permeation enhancing system increased the permeation of both existing drugs formulated in nail lacquers and terbinafine through human nail sections mounted in a modified Franz cell. Furthermore the ATP assay confirmed that the system also enhanced the permeation of terbinafine through infected cadaver nail resulting in a decrease in ATP levels equivalent to those of uninfected negative control samples.

Conclusions
This study has clearly demonstrated that the use of a novel permeation enhancing system, which fundamentally alters the chemical structure of the nail, not only enhances the efficacy of the existing topical formulations but also enables the delivery and efficacy of terbinafine when applied ungually. Such a topically applied system has the possibility of overcoming the systemic side effects when terbinafine is delivered orally.
The application of feature selection to the development of Gaussian process models for percutaneous absorption
Authors: Lam Lun Tak , Sun Yi , Davey Neil , Adams Rod , Prapopoulou Maria , Brown Marc B , Moss Gary P 
Published: September 2015

Abstract

Objectives
The aim was to employ Gaussian processes to assess mathematically the nature of a skin permeability dataset and to employ these methods, particularly feature selection, to determine the key physicochemical descriptors which exert the most significant influence on percutaneous absorption, and to compare such models with established existing models.

Methods
Gaussian processes, including automatic relevance detection (GPRARD) methods, were employed to develop models of percutaneous absorption that identified key physicochemical descriptors of percutaneous absorption. Using MatLab software, the statistical performance of these models was compared with single linear networks (SLN) and quantitative structure–permeability relationships (QSPRs). Feature selection methods were used to examine in more detail the physicochemical parameters used in this study. A range of statistical measures to determine model quality were used.

Key findings
The inherently nonlinear nature of the skin data set was confirmed. The Gaussian process regression (GPR) methods yielded predictive models that offered statistically significant improvements over SLN and QSPR models with regard to predictivity (where the rank order was: GPR &gt; SLN &gt; QSPR). Feature selection analysis determined that the best GPR models were those that contained log P, melting point and the number of hydrogen bond donor groups as significant descriptors. Further statistical analysis also found that great synergy existed between certain parameters. It suggested that a number of the descriptors employed were effectively interchangeable, thus questioning the use of models where discrete variables are output, usually in the form of an equation.

Conclusions
The use of a nonlinear GPR method produced models with significantly improved predictivity, compared with SLN or QSPR models. Feature selection methods were able to provide important mechanistic information. However, it was also shown that significant synergy existed between certain parameters, and as such it was possible to interchange certain descriptors (i.e. molecular weight and melting point) without incurring a loss of model quality. Such synergy suggested that a model constructed from discrete terms in an equation may not be the most appropriate way of representing mechanistic understandings of skin absorption.
The application of molecular structural predictors of intestinal absorption to screening of compounds for transdermal penetration
Authors: Grice Jeffrey E , Cross Sheree E , Brownlie Craig , Roberts Michael S 
Published: September 2015

Abstract

Objectives
The development of methods to predict the transport of molecules across biological membranes, without the need for time-consuming collection of experimental data, is a rapidly growing science. The use of structural characteristics of molecules has been investigated to predict the maximum transport rates of molecules across skin epidermal and intestinal membranes, known as maximum flux and maximum absorbable dose, respectively, although different approaches have been used. The aim of the present study was to determine whether the relationship between polar surface area and number of rotatable bonds of molecules and their permeability through intestinal membranes could be applied to the permeation of solutes through the epidermis following topical application.

Methods
We used a published dataset of human epidermal maximum flux values for 182 solutes and stepwise regression to determine relationships between structural predictors and maximum membrane transport rates.

Key findings
Results showed that diffusion processes occurring across intestinal and skin epidermal membranes cannot be estimated by the same solute molecular properties, as different combinations of partitioning and diffusion processes appear to be dominating in each type of membrane. The basis of these differences in terms of molecular weight dependence and the usefulness of polar surface area are discussed.

Conclusions
Based on available literature, we concluded that transdermal penetration is poorly predicted by parameters derived from intestinal or Caco-2 model membranes. While this approach may be useful for small sets of structurally related compounds, it appears to have limited value for screening and selection of novel structures in the pharmaceutical industry.
Tocopheryl acetate disposition in porcine and human skin when administered using lipid nanocarriers
Authors: Moddaresi Mojgan , Brown Marc B , Tamburic Slobodanka , Jones Stuart A 
Published: September 2015

Abstract

Objectives
Assessing the delivery of a drug into the skin when it has been formulated within a nanocarrier is a complex process that does not conform to the conventions of traditional semi-solid formulations. The aim of this study was to gain a fundamental understanding of drug disposition in both human and porcine skin when applied using a lipidic nanocarrier.

Methods
A model system was generated by loading tocopheryl acetate into a well-characterised solid lipid nanoparticle and formulating this system as a traditional aqueous hyaluronic acid gel. Franz diffusion cells fitted with a silicone or nylon membrane were used to assess drug and particle transport independently whilst human and pig skin were employed to determine skin delivery.

Key findings
The tocopheryl acetate, when loaded into the solid lipid nanoparticles, did not release from the particle. However, 1.65 ± 0.90% of an infinite dose of tocopheryl acetate penetrated into the stratum corneum of pig skin when delivered using a nanoparticle-containing gel.

Conclusions
These results suggest that hydration of the stratum corneum in pig skin could lead to the opening of hydrophilic pores big enough for 50 nm-sized particles to pass into the superficial layers of the skin, a phenomenon that was not repeated in human skin.
Evaluation of the effect of topical agents on radiation-induced skin disease by reflectance spectrophotometry
Authors: Rizza Luisa , D'Agostino Antonio , Girlando Andrea , Puglia Carmelo 
Published: September 2015

Abstract

Objectives
Radiotherapy may cause severe skin changes that significantly interfere with the patient's quality of life and reduce radiotherapy effectiveness. Many skin care instructions and various topical agents are recommended to help patients in the management of radiation skin reactions, but evidence to support the value of the topical treatments of the irradiated skin is lacking. In the present study we investigated the effects of topical agents used as supportive care to minimise radiation-induced skin disease using an instrumental method.

Methods
Subjects who were undergoing a planned course of radiation therapy after breast-conserving surgery were randomised to treatment (using one of two topical agents) or non-treatment (control) groups and monitored over 8 weeks. The intensity of skin erythema was evaluated once per week by non-invasive instrumental reflectance spectrophotometry in comparison with a visual scoring system.

Key findings
Examination of the erythema time course by a sensitive spectrophotometric reflectance method showed a significant increase of skin reactions in the non-treated group after the second week of treatment and maximal alterations between the fourth and sixth week.

Conclusions
From the results obtained, we observed that application of topical agents used in radio-induced skin disease were able to significantly reduce the erythema extent compared to the non-treated group.
Scientific evidence for Mikania laevigata and Mikania glomerata as a pharmacological tool
Authors: Napimoga Marcelo H , Yatsuda Regiane 
Published: September 2015

Abstract

Objectives
Historically, the majority of new drugs have been generated from natural products as well as from compounds derived from natural products. In this context, Mikania laevigata and M. glomerata, popularly known as ‘guaco’, have a long history of use. Brazilian Indians have an ancient tradition of using ‘guaco’ for snakebites. In current herbal medicine in Brazil, ‘guaco’ is used as an effective natural bronchodilator, expectorant and cough suppressant employed for all types of upper respiratory problems including bronchitis, pleurisy, colds and flu, coughs and asthma.

Key findings
In Brazil, this plant has been widely used, even as commercial preparations. Its medicinal properties are widely recognized, mainly in the treatment of inflammatory conditions, bronchodilator activity, anti-ulcerogenic, antiophidian as well as antibacterial and antiparasitic activity, although the efficacy of the antibacterial activity is so far controversial.

Summary
The studies on Mikania glomerata and M. laevigata have provided scientific evidence that those plants have a considerable anti-inflammatory therapeutic potential.