bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabinoid receptor ligands as potential anticancer agents — high hopes for new therapies?
Authors: Oesch Susanne , Gertsch Jürg 
Published: October 2010

AbstractObjectivesThe endocannabinoid system is an endogenous lipid signalling network comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors, transporters and endocannabinoid degrading enzymes. The CB1 receptor is predominantly expressed in neurons but is also co-expressed with the CB2 receptor in peripheral tissues. In recent years, CB receptor ligands, including Δ9-tetrahydrocannabinol, have been proposed as potential anticancer agents.Key findingsThis review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity, tissue specificity and potency. Intriguingly, antitumour effects mediated by cannabinoids are not confined to inhibition of cancer cell proliferation; cannabinoids also reduce angiogenesis, cell migration and metastasis, inhibit carcinogenesis and attenuate inflammatory processes. In the last decade several new selective CB1 and CB2 receptor agents have been described, but most studies in the area of cancer research have used non-selective CB ligands. Moreover, many of these ligands exert prominent CB receptor-independent pharmacological effects, such as activation of the G-protein-coupled receptor GPR55, peroxisome proliferator-activated receptor gamma and the transient receptor potential vanilloid channels.SummaryThe role of the endocannabinoid system in tumourigenesis is still poorly understood and the molecular mechanisms of cannabinoid anticancer action need to be elucidated. The development of CB2-selective anticancer agents could be advantageous in light of the unwanted central effects exerted by CB1 receptor ligands. Probably the most interesting question is whether cannabinoids could be useful in chemoprevention or in combination with established chemotherapeutic agents.
Enhanced skin delivery of quercetin by microemulsion
Authors: Kitagawa Shuji , Tanaka Yuko , Tanaka Manami , Endo Kanako , Yoshii Akiko 
Published: October 2010

Abstract

Objectives
For topical application of quercetin it is necessary to improve the low efficiency of its intradermal delivery as well as its low solubility in aqueous and organic vesicles. The aim of this study was to determine the usefulness of a microemulsion for that purpose.

Methods
A microemulsion consisting of isopropyl myristate, 150 mm NaCl solution, Tween 80 and ethanol was prepared. The skin delivery of quercetin by microemulsion using excised guinea-pig and Yucatan micropig skin in Franz diffusion cells was examined. Lipid peroxidation in skin was also tested using iron(II) and citrate.

Key findings
Using a w/o microemulsion as a vehicle, intradermal delivery of quercetin was significantly increased, as was its solubility. Quercetin penetrated deep into the skin, but no transfer was observed into the receptor compartment. It was confirmed that quercetin retained in the skin dose-dependently inhibited lipid peroxidation.

Conclusions
The findings indicate the potential use of microemulsions for the skin delivery of quercetin, where it exerts antioxidative effects.
Preparation and in-vitro bioactivity of a novel superantigen conjugate targeting bladder carcinoma
Authors: Zhen Gong , Cong-hui Han , Lin Hao , Jian-jun Yang , Wen-hao Tang , Gao-jun Teng 
Published: October 2010

Abstract

Objectives
Superantigens have shown potent effects against bladder tumours by inducing Vβ-specific T-lymphocyte proliferation and massive cytokine release but therapeutic benefit is compromised by cytotoxicity towards non-malignant cells and hypotoxicity to major histocompability complex (MHC) II-negative tumour cells. We are therefore interested in a conjugate preparation of a monoclonal antibody (MAb)—superantigens conjugate for which these drawbacks would be resolved.

Methods
The Fab fragment of the anti-bladder carcinoma MAb BDI-1 was conjugated to one member of the staphylococcal enterotoxin A (SEA) superantigen using the chemical conjugating reagent, N-succinimidyl 3-(2-pyridyldithio) propionate.

Results
After HPLC purification through a Superdex-200 gel column, another peak with a molecular mass of 250 KDa was observed before Fab and SEA were eluted. Indirect immunocytochemical analysis and immunofluorescence tests showed that the cell membranes of most human bladder cancer cells were positively stained only by the conjugate, confirming the ability of the conjugate to target human bladder carcinoma. Peripheral blood mononuclear cell proliferation and cytokine release were similar with the conjugate and SEA. Cytotoxicity targeting in MHC II-negative bladder cancer cell lines, evaluated by flow cytometry, showed significant differences between the conjugate and SEA, whereas there was no difference in the Lovo colon cancer cell line.

Conclusions
These findings indicate the conjugate of SEA protein and BDI-1 Fab fragment was prepared successfully and targeted bladder carcinoma in vitro.
Metabolic interactions with piperazine-based ‘party pill’ drugs
Authors: Antia Ushtana , Tingle Malcolm D , Russell Bruce R 
Published: October 2010

AbstractObjectives‘Party pills’ have found use worldwide as a substitute for amphetamine-derived designer drugs. Whilst some information exists about the metabolism of these drugs, there is little information about their ability to inhibit the metabolism of co-administered drugs. This study aimed to determine whether predictions can be made about global interactions between ‘party pills’ constituents and other drugs metabolised by the same cytochrome P450 (CYP) isoenzymes.MethodsThe inhibitory effects of seven benzyl and phenyl piperazines were measured in microsomal incubation assays of probe substrates for five major CYP isoenzymes. In addition, the metabolism of benzylpiperazine and trifluoromethylphenylpiperazine, the two most commonly used constituents of ‘party pills’, was investigated using human liver microsomes assays and known inhibitors of CYP isoenzymes.Key findingsAll piperazine analogues tested showed significant inhibitory activity against most, if not all, isoenzymes tested. The metabolism of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) involved CYP2D6, CYP1A2 and CYP3A4. Furthermore, BZP and TFMPP inhibited each other's metabolism.ConclusionsFluorophenylpiperazine, methoxyphenylpiperazine, chlorophenylpiperazine, methylbenzylpiperazine and methylenedioxybenzylpiperazine had significant inhibitory effects on CYP2D6, CYP1A2, CYP3A4, CYP2C19 and CYP2C9 isoenzymes but each piperazine had a different inhibitory profile. The metabolic interaction between BZP and TFMPP may have clinical implications, as these agents are often combined in ‘party pills’.
Whole-body physiologically based pharmacokinetic population modelling of oral drug administration: inter-individual variability of cimetidine absorption
Authors: Willmann Stefan , Edginton Andrea N , Kleine-Besten Marcus , Jantratid Ekarat , Thelen Kirstin , Dressman Jennifer B 
Published: October 2010

Abstract

Objectives
Inter-individual variability of gastrointestinal physiology and transit properties can greatly influence the pharmacokinetics of an orally administered drug in vivo. To predict the expected range of pharmacokinetic plasma concentrations after oral drug administration, a physiologically based pharmacokinetic population model for gastrointestinal transit and absorption was developed and evaluated.

Methods
Mean values and variability measures of model parameters affecting the rate and extent of cimetidine absorption, such as gastric emptying, intestinal transit times and effective surface area of the small intestine, were obtained from the literature. Various scenarios incorporating different extents of inter-individual physiological variability were simulated and the simulation results were compared with experimental human study data obtained after oral cimetidine administration of four different tablets with varying release kinetics.

Key findings
The inter-individual variability in effective surface area was the largest contributor to absorption variability. Based on in-vitro dissolution profiles, the mean plasma cimetidine concentration–time profiles as well as the inter-individual variability could be well described for three cimetidine formulations. In the case of the formulation with the slowest dissolution kinetic, model predictions on the basis of the in-vitro dissolution profile underestimated the plasma exposure.

Conclusions
The model facilitates predictions of the inter-individual pharmacokinetic variability after oral drug administration for immediate and extended-release formulations of cimetidine, given reasonable in-vitro dissolution kinetics.
Interaction of morphine but not fentanyl with cerebral α2-adrenoceptors in α2-adrenoceptor knockout mice
Authors: Höcker Jan , Böhm Ruwen , Meybohm Patrick , Gruenewald Matthias , Renner Jochen , Ohnesorge Henning , Scholz Jens , Bein Berthold 
Published: October 2010

AbstractObjectivesα2-Adrenergic and μ-opioid receptors belong to the rhodopsin family of G-protein coupled receptors and mediate antinociceptive effects via similar signal transduction pathways. Previous studies have revealed direct functional interactions between both receptor systems including synergistic and additive effects. To evaluate underlying mechanisms, we have studied whether morphine and fentanyl interacted with α2-adrenoceptor-subtypes in mice lacking one individual α2-adrenoceptor-subtype (α2-adrenoceptor knockout).MethodsOpioid interaction with α2-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of α2A-, α2B- or α2C-adrenoceptor deficient mice. Displacement of the radiolabelled α2-adrenoceptor agonist [125I]paraiodoclonidine from α2-adrenoceptors in different brain regions by increasing concentrations of morphine, fentanyl and naloxone was analysed. The binding affinity of both opioids to α2-adrenoceptor subtypes in different brain regions was quantified.Key findingsMorphine but not fentanyl or naloxone provoked dose-dependent displacement of [125I]paraiodoclonidine from all α2-adrenoceptor subtypes in the brain regions analysed. Binding affinity was highest in cortex, medulla oblongata and pons of α2A-adrenoceptor knockout mice.ConclusionsOur results indicated that morphine interacted with α2-adrenoceptors showing higher affinity for the α2B and α2C than for the α2A subtype. In contrast, fentanyl and naloxone did not show any relevant affinity to α2-adrenoceptors. This effect may have an impact on the pharmacological actions of morphine.
Hexa-, hepta- and nonaprenylhydroquinones isolated from marine sponges Sarcotragus muscarum and Ircinia fasciculata inhibit NF-k B signalling in H4IIE cells
Authors: Wätjen Wim , Putz Annika , Chovolou Yvonni , Kampkötter Andreas , Totzke Frank , Kubbutat Michael H G , Proksch Peter , Konuklugil Belma 
Published: October 2010

Abstract

Objectives
Marine organisms have proven to be a rich source of potent pharmacologically active compounds. Three polyprenyl-1,4-hydroquinone derivates (hexaprenyl-1,4-hydroquinone, heptaprenyl-1,4-hydroquinone and nonaprenyl-1,4-hydroquinone) were isolated from the Zoobenthos-inhabiting sponges Sarcotragus muscarum and Ircinia fasciculata from the Eastern Mediterranean Sea (phylum: Porifera; class: Demospongiae).

Methods
Hexa-, hepta- and nonaprenylhydroquinone were identified by 1H-NMR, H,H-COSY, heteronuclear multiple bond correlation, FAB-MS and UV spectroscopy. The effects of the compounds on cell viability was determined using the MTT assay; anti-oxidative potential was measured using the Trolox equivalent antioxidative capacity assay. Inhibition of nuclear factor-k B activity was detected by secreted alkaline phosphatase assay. Activity against an array of protein kinases was determined in 96-well FlashPlates.

Key findings
All compounds had prominent antioxidative activity, comparable to that of the synthetic vitamin E derivate Trolox. Hexaprenylhydroquinone showed the greatest cytotoxicity in H4IIE hepatoma cells (EC50 2.5 μM). All three compounds inhibited NF-k B signalling in this cell line, with heptaprenylhydroquinone being the most active. Screening of 23 kinases involved in signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) showed that hexaprenylhydroquinone and heptaprenylhydroquinone inhibited the activity of the epidermal growth factor receptor (IC50 1.6 and 1.4 μg/ml, respectively), and heptaprenylhydroquinone also inhibited the activity of other kinases (Src tyrosine kinase, vascular endothelial growth factor receptor 3 and insulin-like growth factor 1 receptor).

Conclusions
The prenylated hydroquinones isolated from the marine sponges S. muscarum and I. fasciculata showed cytotoxic and antioxidative activities and inhibited NF-k B signalling in H4IIE hepatoma cells and protein kinases. These findings may result in the generation of new lead substances in cancer therapy.
Protection afforded by a herbal medicine, Sho-seiryu-to (TJ-19), against oleic acid-induced acute lung injury in guinea-pigs
Authors: Yang Chang-qing , Ishitsuka Yoichi , Moriuchi Hiroshi , Golbidi Saeid , Jin Zhen-ji , Irikura Mitsuru , Irie Tetsumi 
Published: October 2010

Abstract

Objectives
The effect of a herbal medicine, Sho-seiryu-to (TJ-19), on oleic acid-induced lung injury, an animal model of acute respiratory distress syndrome or acute lung injury (ARDS/ALI), was examined.

Methods
Acute lung injury was induced by an intravenous injection of 15 μl/kg oleic acid to guinea-pigs. TJ-19 was administered by a single oral dose (3 g/kg) or by multiple oral doses (0.75 g/kg).

Key findings
The decrease in partial oxygen pressure of arterial blood (Pao2) and the increase in airway vascular permeability induced by the oleic acid injection were attenuated by a single dose of TJ-19. When TJ-19 was administered orally twice a day for two weeks and then oleic acid was injected, a potent prophylactic effect of the drug was observed. TJ-19 also prevented airway vascular hyperpermeability, lung cell injury, oxidative stress and thromboxane A2 generation, associated with the oleic acid injection.

Conclusions
TJ-19 significantly attenuated the oleic acid-induced lung injury probably through the antioxidative effect and inhibitory effect of thromboxane A2 generation, although the precise inhibitory mechanisms were not fully elucidated due to the diversity in constituents of the herbal medicine. We suggest that TJ-19 is a promising drug candidate and a medicinal resource for preventing ARDS/ALI.
Protection of DNA and membranes from gamma-radiation induced damages by Centella asiatica
Authors: Joy Jisha , Nair Cherupally Krishnan Krishnan 
Published: October 2010

Abstract

Objectives
The objective of the present study was to examine the ability of Centella asiatica extract to offer protection to DNA and membranes against the deleterious effects of ionizing radiation exposure.

Methods
Protection of DNA under in-vitro conditions of irradiation was estimated using plasmid relaxation assay. For in-vivo studies the extract was administered orally to mice exposed to whole-body γ-radiation. The ability of the extract to offer protection against whole-body γ-radiation exposure was analysed by performing an alkaline comet assay on mouse bone marrow cells. The extent of lipid peroxidation was estimated using the TBARS (thio-barbituric acid reacting substances) method, in order to monitor membrane damage. Radiation-induced mortality of the animals following a lethal dose of γ-radiation was also examined.

Key findings
Centella asiatica extract significantly reduced radiation-induced damage to DNA. The extent of radiation-induced mortality and lipid peroxidation was also found to be considerably reduced in animals administered with the extract.

Conclusions
Centella asiatica rendered radioprotection to DNA and membranes against radiation exposure, both in vitro and in vivo. We have earlier reported that administration of the extract can prevent a radiation-induced decline in antioxidant enzyme levels. This suggests that radioprotection by Centella asiatica extract could be mediated by mechanisms that act in a synergistic manner, especially involving antioxidant activity.
Characterization of the effect of penehyclidine hydrochloride on muscarinic receptor subtypes mediating the contraction of guinea-pig isolated gastrointestinal smooth muscle
Authors: Xiao Hong-tao , Liao Zhi , Meng Xian-min , Yan Xiao-yan , Chen Shu-jie , Mo Zheng-ji 
Published: October 2010

AbstractObjectivesThe aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea-pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes.MethodsRadioimmune assay was used to determine cAMP levels in isolated guinea-pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes.Key findingsThe results indicated that the relaxing effect of penehyclidine hydro-chloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA2 values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig stomach smooth muscle and decreased the cAMP content in isolated guinea-pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 μmol/1.ConclusionsThe results suggest that penehyclidine hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig gastrointestinal smooth muscle.
Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses
Authors: Carrasco Fábio Ricardo , Schmidt Gustavo , Romero Adriano Lopez , Sartoretto Juliano Luiz , Caparroz-Assef Silvana Martins , Bersani-Amado Ciomar Aparecida , Cuman Roberto Kenji Nakamura 
Published: October 2010

Abstract

Objectives
The immunomodulatory effect of ginger, Zingiber officinale (Zingiberaceae), sage, Salvia officinalis (Lamiaceae) and clove, Syzygium aromaticum (Myrtaceae), essential oils were evaluated by studying humor- and cell-mediated immune responses.

Methods
Essential oils were administered to mice (once a day, orally, for a week) previously immunized with sheep red blood cells (SRBCs).

Key findings
Clove essential oil increased the total white blood cell (WBC) count and enhanced the delayed-type hypersensitivity (DTH) response in mice. Moreover, it restored cellular and humoral immune responses in cyclophosphamide-immunosuppressed mice in a dose-dependent manner. Ginger essential oil recovered the humoral immune response in immunosuppressed mice. Contrary to the ginger essential oil response, sage essential oil did not show any immunomodulatory activity.

Conclusions
Our findings establish that the immunostimulatory activity found in mice treated with clove essential oil is due to improvement in humor- and cell-mediated immune response mechanisms.
Dendrimers as therapeutic agents: a systematic review
Authors: Gajbhiye Virendra , Palanirajan Vijayaraj K , Tekade Rakesh K , Jain Narendra K 
Published: October 2010

Abstract

Objectives
Dendrimers by virtue of their therapeutic value have recently generated enormous interest among biomedical scientists. This review describes the therapeutic prospects of the dendrimer system.

Key findings
Their bioactivity suggests them to be promising therapeutic agents, especially in wound healing, bone mineralisation, cartilage formation and tissue repair, and in topical treatments to prevent HIV transmission. Findings also demonstrate their potential as anti-prion, anti-Alzheimer's, anticoagulant, antidote, anti-inflammatory and anticancer agents. One of the dendrimer-based formulations with activity against herpes simplex virus (VivaGel from Starpharma) has successfully completed phase I clinical trials and is expected to be available on the market soon.

Summary
All reports cited in this review demonstrate the use of dendrimers as medical therapeutics in different ailments. The review focuses on the current state of therapeutic potential of the dendrimer system.
Trypsin as a novel potential absorption enhancer for improving the transdermal delivery of macromolecules
Authors: Li Ying-zhe , Quan Ying-shu , Zang Lei , Jin Mei-na , Kamiyama Fumio , Katsumi Hidemasa , Tsutsumi Sadami , Yamamoto Akira 
Published: October 2010

Abstract

Objectives
The aim was to assess the effect of trypsin on the transdermal delivery of macromolecules by applying its specific biochemical properties to the stratum corneum of the skin.

Methods
Fluorescein isothiocyanate (FITC)-labelled dextrans (FDs), with molecular weights of 4 to 250 kDa, and FITC-insulin were used as model macromolecules and a model polypeptide, and the in-vitro transdermal permeation experiments, with or without trypsin (0.1–2.5%), were carried out using rat skin and cultured human epidermis. The mechanism for the enhancement of trypsin was also studied using fluorescence and conventional light microscopy.

Key findings
Trypsin significantly increased the transdermal permeability of all FDs through the rat skin (2.0- to 10.0-fold). It also markedly enhanced the permeation of FD4 through three-dimensional cultured human epidermis (3.1-fold), which was used to evaluate the transport pathways other than the transfollicular route. Furthermore, the permeation flux of FITC-insulin was increased by 10.0-fold with trypsin pretreatment (from 0.02 ± 0.00 to 0.20 ± 0.07 μg/cm2 per h). Mechanistic studies indicated that trypsin affects both the intercellular pathway and the hair follicular route, and may alter stratum corneum protein structures, thereby affecting skin barrier properties.

Conclusions
This study suggests that trypsin could be effective as a biochemical enhancer for the transdermal delivery of macromolecules including peptide and protein drugs.
Evaluation of percutaneous absorption of the repellent diethyltoluamide and the sunscreen ethylhexyl p-methoxycinnamate-loaded solid lipid nanoparticles: an in-vitro study
Authors: Puglia Carmelo , Bonina Francesco , Castelli Francesco , Micieli Dorotea , Sarpietro Maria Grazia 
Published: October 2010

Abstract

Objectives
Diethyltoluamide and ethylhexyl p-methoxycinnamate (OMC) are two active ingredients in insect repellent and sunscreen products, respectively. The concurrent application of these two substances often increases their systemic absorption, compromising the safety and efficiency of the cosmetic product. In this study, diethyltoluamide and OMC were incorporated into solid lipid nanoparticles, a colloidal drug delivery system, to reduce percutaneous absorption and avoid toxic effects and also maintain the efficacy of the two active compounds on the skin surface for a long duration.

Methods
Solid lipid nanoparticles were prepared based on an ultrasonication technique and characterized by differential scanning calorimetry (DSC) analyses. In-vitro studies determined the percutaneous absorption of diethyltoluamide and OMC.

Key findings
DSC data carried out on unloaded and diethyltoluamide- and/or OMC-loaded solid lipid nanoparticles highlighted that diethyltoluamide and OMC modified the temperature and the enthalpy change associated to the calorimetric peak of solid lipid nanoparticles. The concurrent presence of the two compounds in the solid lipid nanoparticles caused a synergic effect, indicating that the lipid matrix of nanoparticles guaranteed a high encapsulation of both diethyltoluamide and OMC. Results from the in-vitro study demonstrated that the particles were able to reduce the skin permeation of the two cosmetic ingredients in comparison with an oil-in-water emulsion.

Conclusions
This study has provided supplementary evidence as to the potential of lipid nanoparticles as carriers for topical administration of cosmetic active compounds.