bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of inducible nitric oxide synthesis by Cimicifuga racemosa (Actaea racemosa, black cohosh) extracts in LPS-stimulated RAW 264.7 macrophages
Authors: Schmid Diethart , Gruber Miriam , Woehs Florian , Prinz Sonja , Etzlstorfer Barbara , Prucker Christina , Fuzzati Nicola , Kopp Brigitte , Moeslinger Thomas 
Published: October 2010

Abstract

Objectives
Cimicifuga racemosa (Actaea racemosa, black cohosh) is used as an anti-inflammatory, antipyretic and analgesic remedy in traditional medicines. The present study focuses on the effects of C. racemosa root extracts on inducible nitric oxide synthase (iNOS) in lipopolysaccharide-stimulated murine macrophages (RAW 264.7).

Methods
C. racemosa rhizome and phosphate-buffered saline extracts were analysed for phenolcarboxylic acids and triterpene glycosides using an HPLC photodiode array/evaporative light-scattering detector system. iNOS was characterised by measurement of iNOS protein (immunoblotting), iNOS mRNA (semiquantitative competitive RT-PCR), nitric oxide production (nitrite levels) and nuclear translocation of nuclear factor-kB (p65 subunit) protein.

Key findings
Incubation of lipopolysaccharide-stimulated macrophages with aqueous C. racemosa extracts (0–6 mg/ml) inhibited nitrite accumulation in a concentration-dependent manner. C. racemosa extracts also reduced iNOS protein expression and iNOS mRNA levels in a dose-dependent manner. C. racemosa extracts did not significantly inhibit iNOS activity and did not affect nuclear translocation of nuclear factor-kB (p65 subunit) protein. Incubation with the extract was associated with a concentration-dependent reduction of interferon beta and interferon regulatory factor 1 mRNA. Among the triterpene glycosides, 23-epi-26-deoxyactein was identified as an active principle in C. racemosa extracts.

Conclusions
Extracts from the roots of C. racemosa inhibit nitric oxide production by reducing iNOS expression without affecting activity of the enzyme. This might contribute to the anti-inflammatory activities of C. racemosa.
The application of Gaussian processes in the prediction of percutaneous absorption
Authors: Moss Gary P , Sun Yi , Prapopoulou Maria , Davey Neil , Adams Rod , Pugh W John , Brown Marc B 
Published: October 2010

Abstract

Objectives
The aim was to assess mathematically the nature of a skin permeability dataset and to determine the utility of Gaussian processes in developing a predictive model for skin permeability, comparing it with existing methods for deriving predictive models.

Methods
Principal component analysis was carried out in order to determine the nature of the dataset. MatLab software was used to assess the performance of Gaussian process, single linear networks (SLN) and quantitative structure-permeability relationships (QSPRs) using a range of statistical measures.

Key findings
Principal component analysis showed that the dataset is inherently nonlinear. The Gaussian process model yielded a predictive model that provides a significantly more accurate estimate of skin absorption than previous models, particularly QSPRs (which were consistently worse than Gaussian process or SLN models), and does so across a wider range of molecular properties. Gaussian process models appear particularly capable of providing excellent predictions where previous studies have shown QSPRs to fail, such as where penetrants have high log P and high molecular weight.

Conclusions
A non-linear approach was more appropriate than QSPRs or SLNs for the analysis of the dataset employed herein, as the prediction and confidence values in the prediction given by the Gaussian process are better than with other methods examined. Gaussian process provides a novel way of analysing skin absorption data that is substantially more accurate, statistically robust and reflective of our empirical understanding of skin absorption than the QSPR methods so far applied to skin absorption.
Mannose 6-phosphate-modified bovine serum albumin nanoparticles for controlled and targeted delivery of sodium ferulate for treatment of hepatic fibrosis
Authors: Li Feng-Qian , Su Hua , Chen Xu , Qin Xian-Ju , Liu Ji-Yong , Zhu Quan-Gang , Hu Jin-Hong 
Published: October 2010

Abstract

Objectives
The aim was to prepare neoglycoprotein-based nanoparticles for targeted drug delivery to hepatic stellate cells, and to evaluate their characteristics in vitro and in vivo.

Methods
The neoglycoprotein of bovine serum albumin modified with mannose 6-phosphate was synthesised from mannose, and used as wall material to nanoencapsulate the model natural antifibrotic substance sodium ferulate using a desolvation method. The morphology, drug loading capacity, release in vitro and biodistribution in vivo of the nanoparticles were studied. Selectivity of the nanoparticles for hepatic stellate cells was evaluated by immunohistochemical analysis of fibrotic rat liver sections.

Key findings
The spherical nanoparticles were negatively charged with zeta potential ranging from −2.73 to −35.85 mV, and sizes between 100 and 200 nm with a narrow size distribution. Drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) could be achieved. In vitro, the nanoparticles showed an initial rapid continuous release followed by a slower sustained release. After intravenous injection into mice, the nanoparticles showed a slower elimination rate and a much higher drug concentration in liver compared with the sodium ferrate solution, and less distribution to the kidneys and other tissues. Immunohistochemistry indicated that the neoglycoprotein-based nano-particles were taken up specifically by hepatic stellate cells.

Conclusions
The nanoparticles may be an efficient drug carrier targeting hepatic stellate cells.
Reduction of Staphylococcus aureus and Pseudomonas aeruginosa colonisation on PVC through covalent surface attachment of fluorinated thiols
Authors: McCoy Colin P , Cowley John F , Gorman Sean P , Andrews Gavin P , Jones David S 
Published: October 2010

Abstract

Objectives
This study reports the development, characterisation and microbiological testing of surface-modified polyvinylchloride (PVC) films for the purpose of reducing bacterial adherence.

Methods
Irreversible covalent surface modification was achieved via nucleophilic substitution of fluorinated thiol-terminated compounds onto the polymer backbone. Four fluorinated modifiers, 2,3,5,6-tetrafluorothiophenol (TFTP), 4-(trifluoromethyl)thiophenol (TFMTP), 3,5-bis(trifluoromethyl)benzenethiol (BTFMBT) and 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-decane-1-thiol (HDFDT), were investigated. Modification was confirmed using attenuated total reflectance infrared spectroscopy; Raman mapping demonstrated that modification was homogenous on the macroscopic scale. The influence of fluorination on surface hydrophobicity was studied by contact angle analysis. The effect on microbial adherence was examined using Pseudomonas aeruginosa and Staphylococcus aureus.

Key findings
The resultant changes in contact angle relative to control PVC ranged from −4° to +14°. In all cases, adherence of P. aeruginosa and S. aureus was significantly reduced relative to control PVC, with adherence levels ranging from 62% and 51% for TFTP-modified PVC to 32% and 7% for TFMTP-modified PVC.

Conclusions
These results demonstrate an important method in reducing the incidence of bacterial infection in PVC medical devices without compromising mechanical properties.
Freeze-dried liposomes as potential carriers for ocular administration of cytochrome c against selenite cataract formation
Authors: Zhang Jing , Guan Peipei , Wang Tianyi , Chang Di , Jiang Tongying , Wang Siling 
Published: October 2010

Abstract

Objectives
In this study, the preparation, stability and anti-cataract effect of cationic freeze-dried liposomes containing cytochrome c, along with nicotinamide and adenosine, are described.

Methods
Cytochrome c-loaded cationic liposomes (CC-L) were prepared by the thin-layer evaporation technique and lyophilized to obtain freeze-dried cytochrome c liposomes (CC-F). The influence of the preparation components on the liposomal encapsulation efficiency and the stability were studied. The anti-cataract effect of the CC-F was demonstrated through attenuating lens opacity development with slit lamp examination in rats with selenite-induced cataract.

Key findings
Our study indicates that: (1) the liposomal encapsulation efficiency increased with increasing phosphatidylcholine content and reduced in the presence of stearylamine. Moreover, optimal encapsulation efficiency was obtained at an appropriate ratio of phosphatidylcholine to cholesterol; (2) CC-F was stable for at least 12 months at 4°C; (3) satisfactory improvements in lens opacity were shown in the cytochrome c-treated groups, especially for the CC-F-treated group with the decreased percentage of lens opacity at about 28% at the final examination.

Conclusions
CC-F were shown to be stable superior ophthalmic carriers and were able to markedly retard the onset of cataract development.
Novel pepper extract for enhanced P-glycoprotein inhibition
Authors: Aher Suyog , Biradar Shailesh , Gopu C L , Paradkar Anant 
Published: October 2010

AbstractObjectivesPiperine is one of the most promising bioenhancers to date. Methods used for its extraction suffer from drawbacks such as use of organic solvents, poor extraction efficiency, tedious and expensive methodology. These methods are not encouraged with a view to reducing global warming. The objective was therefore to develop an alternative solvent-free extraction method.MethodsAn aqueous extract of long pepper fruits was prepared using hydrophilic lipid Gelucire 44/14 as the extracting aid and this was compared with an alcoholic extract. Extracts were characterized using high-performance thin layer chromatography and differential scanning calorimetry. P-glycoprotein (P-gp) inhibitory activity of the aqueous and alcoholic extracts and pure piperine was compared using an in-vitro everted rat intestinal model using ornidazole as the model drug. The study was performed using two oral pretreatment dose levels (10 and 20 mg/kg) and durations (1 and 3 days). Exsorption of ornidazole from serosal to mucosal surface was monitored.Key findingsP-gp inhibitory activity of the aqueous extract was comparable with that of pure piperine (P &gt; 0.05) and was significantly higher than the alcoholic extract (P &lt; 0.05). Pure piperine and the aqueous extract exhibited significant P-gp inhibitory activity compared with control, which was irrespective of oral pretreatment dose and duration levels. No significant effect of oral pretreatment duration of the aqueous extract was observed. The observed enhancement in P-gp inhibitory activity of the aqueous extract may have been attributed to the P-gp inhibitory potential of Gelucire 44/14 and its efficient extraction and solubility enhancement ability.ConclusionsIn the field of phytopharmaceuticals efficient and eco-friendly extraction processes are still a goal to be achieved. Extraction with Gelucire 44/14 could be a potential method of extraction for phytopharmaceuticals. Compared with conventional methods of extraction it is more efficient, easier to prepare, eco-friendly and scalable.
Permeability of a novel β-lactamase inhibitor LK-157 and its ester prodrugs across rat jejunum in vitro
Authors: Igličar Petra , Legen Igor , Vilfan Gregor , Selič Lovro , Preželj Andrej 
Published: October 2010

Abstract

Objectives
LK-157 is a novel 10-ethylidene tricyclic carbapenem that resembles the structure of the broad-spectrum antibiotic sanfetrinem and acts as a potent inactivator of β-lactamases of classes A, C and D. LK-157 is a highly soluble but poorly permeable drug. Since most of the β-lactams are poorly absorbed, ester prodrugs LK-159, LK-157E1 and LK-157E2 were designed to enhance membrane permeability. This study investigated the permeability of LK-157 and the three ester prodrugs across rat intestine in vitro. The morpholinoethyl ester of sanfetrinem was also investigated.

Method
Permeability across rat jejunum was determined using EasyMount side-by-side diffusion chambers.

Key findings
The solubility and permeability of morpholinoethyl ester LK-157E2 were superior to those of LK-159 and LK-157E1. The morpholinoethyl ester of sanfetrinem LK-176E1 had the highest observed permeability coefficient and consequently the highest predicted absorption in humans.

Conclusions
These results suggest that the morpholinoethyl esters of LK-157 and sanfetrinem could be further investigated to assess bioavailability in vivo.
Synthesis of a quaternary bis derivative of imipramine as a novel compound with potential anti-enuretic effect
Authors: Jamali Bardia , Roodsari Mahmoodreza Sadeghipoor , Soleymani Zohre , Faizi Mehrdad , Shafaghi Bijan , Kobarfard Farzad 
Published: October 2010

Abstract

Objectives
Imipramine has been used for over four decades (early reports in 1960s) for the treatment of nocturnal enuresis, although the reason for its effect is not clear. Imipramine is a tertiary amine, which may act both in the periphery and/or pass through the blood-brain barrier (BBB) in unionized form and exhibit a central effect. Since imipramine has anti-cholinergic properties, some believe it may exert its anti-enuretic effect by affecting peripheral cholinergic receptors, i.e. its anti-enuretic effect may be due to peripheral anti-cholinergic properties, whereas others think it can pass through the BBB and interact with central nervous system (CNS) receptors. If the anti-enuretic effect of imipramine is due to its peripheral anti-cholinergic effects, its entrance into the CNS is unnecessary. Therefore, the synthesis of a form of imipramine that can exhibit peripheral anti-cholinergic effects but does not have CNS adverse effects would have a safer drug profile in this case. On the other hand, if the anti-enuretic effect of imipramine is primarily due to its action on the CNS, a form of imipramine that cannot pass through the BBB has no effect on nocturnal enuresis treatment and thus may help to clarify the mechanism of action of imipramine in nocturnal enuresis treatment.

Methods
This article describes the synthesis and evaluation of the anti-cholinergic effect of a new bis derivative of imipramine, which contains two imipramine units in its structure.

Key findings
The compound exhibited anti-cholinergic activity comparable with that of imipramine on isolated guinea pig ileum.

Conclusions
Being a quaternary ammonium, this compound is not expected to be able to cross the BBB and thus would cause fewer CNS side effects.
Importance of pharmaceutical composition and evidence from clinical trials and pharmacological studies in determining effectiveness of chondroitin sulphate and other glycosaminoglycans: a critique
Authors: Rainsford K D 
Published: October 2010

Abstract

Objectives
Chondroitin sulphate (CS) has attracted much interest over the past two decades or so as a biological agent for use in the relief of pain and joint symptoms in osteoarthritis. Earlier clinical investigations produced variable, if encouraging results. This variability was partly due to limitations on the study designs and the lack of availability of standardized CS. Recently, high quality and fully standardized CS (Condrosulf) has become available and its effects have been studied in large-scale osteoarthritis trials, which are discussed here.

Key findings
There is now evidence for symptom - and structure-modifying (radio-logically-observed) effects. These studies show that CS (a) has slow onset of response and that relief of pain may not be like that of the direct analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs), (b) there are indications of reduced need for intake of analgesics (e.g. NSAIDs) in patients taking CS, and (c) quality of life and cost-benefits may be associated with use of CS. Safety evaluations show that the incidence of adverse reactions is low. Pharmacokinetic studies indicate that although oral absorption is relatively fast CS has moderate oral bioavailability (15–24%) and that depolymerised and degraded CS that is evident after absorption, together with CS itself, may take some time to accumulate in target joints. The pharmacodynamic actions of CS indicate that it has anti-inflammatory effects that include multiple actions involving reduction of catabolic reactions and enhanced anabolic (proteoglycan) synthetic reactions in cartilage and may block osteoclast activation in bone. Further studies are required to (a) establish the effects of depolymerised and degraded CS on degradation of cartilage and bone in vitro, and (b) MRI and other investigations of the effects in osteoarthritis of long-term CS treatment.

Summary
The findings from this review show there may be potential value of CS in reducing the dependence on intake of NSAIDs and analgesics in patients with osteoarthritis, while at the same time having favourable safety.
Quality of different chondroitin sulfate preparations in relation to their therapeutic activity
Authors: Volpi Nicola 
Published: October 2010

Abstract

Objectives
Chondroitin sulfate is currently recommended by the European League Against Rheumatism (EULAR) as a SYSADOA (symptomatic slow acting drug for osteoarthritis) in Europe in the treatment of knee and hand osteoarthritis based on research evidence and meta-analysis of numerous clinical studies. Furthermore, recent clinical trials demonstrated its possible structure-modifying effects. Chondroitin sulfate, alone or in combination with glucosamine or other ingredients, is also utilized as a nutraceutical in dietary supplements in Europe and the USA. However, it is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants and many other factors contribute to the overall biological and pharmacological actions of these agents. We aim to review the quality control of chondroitin sulfate in pharmaceutical-grade preparations and nutraceuticals.

Key findings
Pharmaceutical-grade formulations of chondroitin sulfate are of high and standardized quality, purity and properties, due to the stricter regulations to which this drug is subjected by local national health institutes as regards production and characteristics. On the contrary, as several published studies available in literature indicate, the chondroitin sulfate quality of several nutraceuticals is poor. Additionally, there are no definite regulations governing the origin of the ingredients in these nutraceuticals and the origin of the ingredients in natural products is the most important factor ensuring quality, and thus safety and efficacy, in particular for chondroitin sulfate, due to its extraction from different sources.

Conclusions
Due to the poor chondroitin sulfate quality of some nutraceuticals, we conclude that stricter regulations regarding their quality control should be introduced to guarantee the manufacture of high quality products for nutraceutical utilization and to protect customers from low-quality, ineffective and potentially dangerous products. There is a need for specific and accurate analytical procedures, which should be enforced to confirm purity and label claims both for raw materials and finished chondroitin sulfate products, and also to govern the origin of ingredients. Until these stricter regulations are in place, then it is strongly recommended that pharmaceutical-grade chondroitin sulfate is used rather than food supplements.
Arsthinol nanosuspensions: pharmacokinetics and anti-leukaemic activity on NB4 promyelocytic leukaemia cells
Authors: Ajana Imane , Astier Alain , Gibaud Stéphane 
Published: October 2010

Abstract

Objectives
The organoarsenical arsthinol was used in the 1950s in the treatment of amoebiasis and yaws and was considered as ‘highly tolerated’. The aim of this work was to study its anti-leukaemic activity and to develop nanosuspensions of the drug, thereby limiting brain concentrations and the risk of encephalopathy.

Methods
Arsthinol nanosuspensions were produced by high-pressure homogenization. The anti-leukaemic activity was assessed on NB4 acute promyelocytic leukaemia cells (vs solutions of arsthinol, As2O3 and melarsoprol). In addition, a pharmacokinetics study was performed to compare the nanosuspensions and the solution of arsthinol.

Key findings
Arsthinol induced growth inhibition of NB4 cells at lower concentration (IC50 (concentration inhibiting growth by 50%) = 0.78 ± 0.08 μmol/l after 24 h) than As2O3 (IC50 = 1.60 ± 0.23 μmol/l after 24 h) or melarsoprol (IC50 = 1.44 ± 0.08 μmol/l after 24 h). When formulated as nanosuspension, arsthinol remained cytotoxic (IC50 = 1.33 ± 0.30 μmol/l after 24 h). This formulation also reduced the drug's access to the brain (Cmax = 0.03 μmol/g) whereas bone marrow concentrations remained very high (Cmax = 2 μmol/g).

Conclusions
Nanosuspensions of arsthinol could be proposed for further studies in the treatment of acute promyelocytic leukaemia.
Acetoside inhibits α-MSH-induced melanin production in B16 melanoma cells by inactivation of adenyl cyclase
Authors: Song Ho Sun , Sim Sang Soo 
Published: October 2010

AbstractObjectivesThe aim of the study was to determine the mechanism of the whitening effect of acteoside.MethodsWe used tyrosinase activity and melanin production stimulated in B16 melanoma cells by α-melanocyte stimulating hormone (α-MSH) or forskolin to measure the whitening effect of acteoside.Key findingsActeoside did not directly inhibit mushroom tyrosinase activity, but dose-dependently inhibited tyrosinase activity and melanin production in B16 melanoma cells stimulated by 1 μmol/l α-MSH. Acteoside also reduced cyclic AMP levels in cells stimulated by 1 μmol/l α-MSH, suggesting direct inhibition of adenyl cyclase. Acteoside also inhibited productionofbothmelanin and cyclic AMP in cells stimulated by 1 μmol/l forskolin, an adenyl cyclase activator. Acteoside showed antioxidant activity in a cell-free DPPH (1-diphenyl-2-picrylhydroazyl) assay and inhibited generation of intracellular reactive oxygen species.ConclusionsThese results suggest that the whitening activity of acteoside results from inhibition of adenyl cyclase and α-MSH signalling.
Intestinal inflammation and seizure susceptibility: understanding the role of tumour necrosis factor-α in a rat model
Authors: Medhi Bikash , Prakash Ajay , Avti Pramod K , Chakrabarti Amitava , Khanduja Krishan L 
Published: October 2010

Abstract

Objectives
The aim of the study was to evaluate the correlation between colitis and susceptibility to seizures.

Methods
Colitis was induced in Wistar rats by a single intracolonic administration of trinitrobenzene sulfonic acid (TNBS; 20 mg in 35% ethanol). The control group were given intracolonic vehicle. One group of rats with colitis were treated with thalidomide (150 mg/kg p.o.) daily for 14 days. The other colitis group received vehicle only. On day 15, seizure susceptibility was tested by administration of pentylenetetrazole (40 mg/kg i.p.). Colonic tissue was collected for estimation of morphological score, and malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase. Tumour necrosis factor (TNF)-α levels were measured in serum and brain samples.

Key findings
The colitis group showed a significant increase in seizure score and reduction in onset time compared with the control group. Thalidomide was protective against seizures, resulting in decreased seizure score and significantly delaying the onset of seizures. Thalidomide also provided significant protection against TNBS-induced colonic damage in terms of morphological and histological score and levels of lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase in colonic tissue. The level of TNF-α in serum was also reduced significantly whereas brain TNF-α level was reduced but not significantly.

Conclusions
TNBS-induced colitis increased seizure susceptibility to a subconvulsive dose of pentylenetetrazole; the immunomodulator thalidomide was protective.