bluuebunny/crossref_metadata_2025 huggingface dataset:
Free Radical Scavenging Activity and Characterization of Sesquiterpenoids in Four Species of Curcuma Using a TLC Bioautography Assay and GC-MS Analysis
Authors: Zhao Jing , Zhang Jiang-sheng , Yang Bin , Lv Guang-Ping , Li Shao-Ping
Published: October 2010

The sesquiterpenoids are one of major groups of antioxidants in Curcuma besides curcuminoids. However, the real substances contributing to the antioxidant activity are still unknown. In this paper, the antioxidant activity of sesquiterpenoids in four species and two essential oils from Curcuma genus was determined and compared based on TLC separation and DPPH bioautography assay. Their antioxidant capacities were quantitatively evaluated using densitometry with detection at 530 nm (λreference = 800 nm) using vitamin C as reference. The results showed that Curcuma longa rhizomes had the highest antioxidant capacity while C. phaeocaulis presented the lowest one among the four species of Curcuma. Moreover, essential oil of C. wenyujin showed higher antioxidant potential than that of C. longa. The main TLC bands with antioxidant activity of the four species of Curcuma were collected and characterized using GC-MS, and thus curzerene, furanodiene, α-turmerone, β-turmerone and β-sesquiphellandrene were determined as major sesquiterpenoids with antioxidant activity in Curcuma.
Antifungal Activity of the Essential Oil of Illicium verum Fruit and Its Main Component trans-Anethole
Authors: Huang Yongfu , Zhao Jianglin , Zhou Ligang , Wang Jihua , Gong Youwen , Chen Xujun , Guo Zejian , Wang Qi , Jiang Weibo
Published: October 2010

In order to identify natural products for plant disease control, the essential oil of star anise (Illicium verum Hook. f.) fruit was investigated for its antifungal activity on plant pathogenic fungi. The fruit essential oil obtained by hydro-distillation was analyzed for its chemical composition by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). trans-Anethole (89.5%), 2-(1-cyclopentenyl)-furan (0.9%) and cis-anethole (0.7%) were found to be the main components among 22 identified compounds, which accounted for 94.6% of the total oil. The antifungal activity of the oil and its main component trans-anethole against plant pathogenic fungi were determined. Both the essential oil and trans-anethole exhibited strong inhibitory effect against all test fungi indicating that most of the observed antifungal properties was due to the presence of trans-anethole in the oil, which could be developed as natural fungicides for plant disease control in fruit and vegetable preservation.
Synthesis and Characterization of a Ru(II) Complex with Functionalized Phenanthroline Ligands Having Single-Double Linked Anthracenyl and 1-Methoxy-1-buten-3-yne Moieties
Authors: Adeloye Adewale O. , Ajibade Peter A.
Published: October 2010

Two series of bidentate polypyridine ligands, made of phenanthroline chelating subunits having substituted mono-and di-anthracenyl groups, and 1-methoxy-1-buten-3-yne at the 4 and 7-positions with the corresponding heteroleptic Ru(II) complex have been synthesized and characterized. The complex is formulated as [(Ru(L1)(L2)(NCS)2)], (where L1 = 4-(9-dianthracenyl-10-(2,3-dimethylacrylic acid)-7-(9-anthracenyl-10-(2,3-dimethylacrylic acid)-1,10-phenanthroline and L2 = 4,7-bis(1-methoxy-1-buten-3-yne)-1,10-phenanthroline). The Ru(II) complex shows characteristic broad and intense metal-to-ligand charge transfer (MLCT) bands absorption and appreciable photoluminescence spanning the visible region. The ligands and complex were characterized by FT-IR, 1H, 13C NMR spectroscopy, UV-Vis, photoluminescence and elemental analysis (see in supplementary materials). The anchoring groups in both ligands have allowed an extended delocalization of acceptor orbital of the metal-to-ligand charge-transfer (MLCT) excited state.
Synthesis and Application in Polypropylene of a Novel of Phosphorus-Containing Intumescent Flame Retardant
Authors: Zuo Jian-Dong , Liu Shu-Mei , Sheng Qi
Published: October 2010

A novel phosphorus-containing triazine oligomer poly(2-morpholinyl-4-penta-erythritol phosphate-1,3,5-triazine) (PMPT) was synthesized as a kind of tri-component intumescent flame retardant (IFR). The chemical structure of PMPT was characterized by FTIR, 1H-NMR and 31P-NMR, and the mechanical and flammability properties of FR-PP were measured. The FTIR results showed that the expected chemical reactions had happened at each step. The 1H-NMR and 31P-NMR spectra also agreed with the chemical structure of PMPT. The slight effect of PMPT on the mechanical properties of FR-PP suggested that PMPT and PP are compatible. The high limited oxygen index (LOI) values of FR-PP revealed that PMPT was an efficient IFR and there was the synergistic effect between PMPT and ammonium polyphosphate/ pentaerythritol (APP/PER).
Inactivation of Anandamide Signaling: A Continuing Debate
Authors: Khairy Hesham , Houssen Wael E.
Published: October 2010

Since the first endocannabinoid anandamide was identified in 1992, extensive research has been conducted to characterize the elements of the tightly controlled endocannabinoid signaling system. While it was established that the activity of endocannabinoids are terminated by a two-step process that includes cellular uptake and degradation, there is still a continuing debate about the mechanistic role of these processes in inactivating anandamide signals.
Nanomedicine Faces Barriers
Authors: Debbage Paul , Thurner Gudrun C.
Published: October 2010

Targeted nanoparticles have the potential to improve drug delivery efficiencies by more than two orders of magnitude, from the ~ 0.1% which is common today. Most pharmacologically agents on the market today are small drug molecules, which diffuse across the body’s blood-tissue barriers and distribute not only into the lesion, but into almost all organs. Drug actions in the non-lesion organs are an inescapable part of the drug delivery principle, causing “side-effects” which limit the maximally tolerable doses and result in inadequate therapy of many lesions. Nanoparticles only cross barriers by design, so side-effects are not built into their mode of operation. Delivery rates of almost 90% have been reported. This review examines the significance of these statements and checks how far they need qualification. What type of targeting is required? Is a single targeting sufficient? What new types of clinical challenge, such as immunogenicity, might attend the use of targeted nanoparticles?
Enhanced Dissolution and Oral Bioavailability of Piroxicam Formulations: Modulating Effect of Phospholipids
Authors: Mirza Sabiruddin , Miroshnyk Inna , Habib Muhammad J. , Brausch James F. , Hussain Muhammad D.
Published: October 2010

Several biologically relevant phospholipids were assessed as potential carriers/additives for rapidly dissolving solid formulations of piroxicam (Biopharmaceutics Classification System Class II drug). On the basis of in vitro dissolution studies, dimyristoylphosphatidylglycerol (DMPG) was ranked as the first potent dissolution rate enhancer for the model drug. Subsequently, the solid dispersions of varying piroxicam/DMPG ratios were prepared and further investigated. Within the concentration range studied (6.4-16.7 wt %), the dissolution rate of piroxicam from the solid dispersions appeared to increase as a function of the carrier weight fraction, whereas the cumulative drug concentration was not significantly affected by piroxicam/DMPG ratio, presumably due to a unique phase behavior of the aqueous dispersions of this carrier phospholipid. Solid state analysis of DMPG-based formulations reveled that they are two-component systems, with a less thermodynamically stable form of piroxicam (Form II) being dispersed within the carrier. Finally, oral bioavailability of piroxicam from the DMPG-based formulations in rats was found to be superior to that of the control, as indicated by the bioavailability parameters, cmax and especially Tmax (53 µg/mL within 2 h vs. 39 µg/mL within 5.5 h, respectively). Hence, DMPG was regarded as the most promising carrier phospholipid for enhancing oral bioavailability of piroxicam and potentially other Class II drugs.
Novel Designs for Application Specific MEMS Pressure Sensors
Authors: Fragiacomo Giulio , Reck Kasper , Lorenzen Lasse , Thomsen Erik V.
Published: October 2010

In the framework of developing innovative microfabricated pressure sensors, we present here three designs based on different readout principles, each one tailored for a specific application. A touch mode capacitive pressure sensor with high sensitivity (14 pF/bar), low temperature dependence and high capacitive output signal (more than 100 pF) is depicted. An optical pressure sensor intrinsically immune to electromagnetic interference, with large pressure range (0–350 bar) and a sensitivity of 1 pm/bar is presented. Finally, a resonating wireless pressure sensor power source free with a sensitivity of 650 KHz/mmHg is described. These sensors will be related with their applications in harsh environment, distributed systems and medical environment, respectively. For many aspects, commercially available sensors, which in vast majority are piezoresistive, are not suited for the applications proposed.
An Agenda-Based Routing Protocol in Delay Tolerant Mobile Sensor Networks
Authors: Wang Xiao-Min , Zhu Jin-Qi , Liu Ming , Gong Hai-Gang
Published: October 2010

Routing in delay tolerant mobile sensor networks (DTMSNs) is challenging due to the networks’ intermittent connectivity. Most existing routing protocols for DTMSNs use simplistic random mobility models for algorithm design and performance evaluation. In the real world, however, due to the unique characteristics of human mobility, currently existing random mobility models may not work well in environments where mobile sensor units are carried (such as DTMSNs). Taking a person’s social activities into consideration, in this paper, we seek to improve DTMSN routing in terms of social structure and propose an agenda based routing protocol (ARP). In ARP, humans are classified based on their agendas and data transmission is made according to sensor nodes’ transmission rankings. The effectiveness of ARP is demonstrated through comprehensive simulation studies.
An Adaptive Fault-Tolerant Communication Scheme for Body Sensor Networks
Authors: Wu Guowei , Ren Jiankang , Xia Feng , Xu Zichuan
Published: October 2010

A high degree of reliability for critical data transmission is required in body sensor networks (BSNs). However, BSNs are usually vulnerable to channel impairments due to body fading effect and RF interference, which may potentially cause data transmission to be unreliable. In this paper, an adaptive and flexible fault-tolerant communication scheme for BSNs, namely AFTCS, is proposed. AFTCS adopts a channel bandwidth reservation strategy to provide reliable data transmission when channel impairments occur. In order to fulfill the reliability requirements of critical sensors, fault-tolerant priority and queue are employed to adaptively adjust the channel bandwidth allocation. Simulation results show that AFTCS can alleviate the effect of channel impairments, while yielding lower packet loss rate and latency for critical sensors at runtime.
The Story of My Face: How Environmental Stewards Perceive Stigmatization (Re)produced By Discourse
Authors: Gutberlet Jutta , Jayme Bruno de Oliveira
Published: October 2010

The story of my face intertwines concepts of social semiotics and discourse analysis to explore how a simple type of printed media (flyer) can generate stigmatization of informal recyclers, known as binners in Western Canada. Every day, media exposes humans to signifiers (e.g., words, photographs, cartoons) that appear to be trivial but influence how we perceive their meaning. Amongst the signifiers frequently found in the media, the word “scavengers”, has been used to refer to autonomous recyclers. Specific discourse has the potential to promote and perpetuate discrimination against the individuals who deal with selective collection of recyclables and decrease the value of their work. Their work is valuable because it generates income for recyclers, recovers resources and improves overall environmental health. In this context, the present qualitative study draws on data collected with binners during research conducted in the city of Victoria, in British Columbia. First we analyze a dialogue between binners from a participatory video workshop, to explore their perceptions of the stigma they suffer. Second we use a flyer produced by the local government alerting against scavenging to illustrate how the content (i.e., structural organization [text and images] in which they are embedded work together to mediate stigmatization against recyclers. Third, we analyze videotaped data from a panel discussion with local government, the local community, and binners on inclusive waste management, to uncover different negative perceptions of binners. In our study we look at the official discourse that marginalizes informal recyclers and creates social injustices. We illustrate how the recyclers perceive stigma and suggest that marginalization could be overcome by reiterating the image of environmental stewards instead of scavengers.
Sustaining Rainforest Plants, People and Global Health: A Model for Learning from Traditions in Holistic Health Promotion and Community Based Conservation as Implemented by Q’eqchi’ Maya Healers, Maya Mountains, Belize
Authors: Rojas Marco Otarola , Collins Sean , Cal Victor , Caal Francisco , Knight Kevin , Arnason John , Poveda Luis , Sanchez-Vindas Pablo , Pesek Todd
Published: October 2010

The present work showcases a model for holistic, sustainable healthcare in indigenous communities worldwide through the implementation of traditional healing practices. The implementation of this model promotes public health and community wellness while addressing crucially important themes such as in situ and ex situ conservation of medicinal plant resources and associated biodiversity, generational transmission of knowledge, and the preservation of biological and cultural diversity for future generations. Being envisaged and implemented by Q’eqchi’ Maya traditional healers of the southern Maya Mountains, Belize, this model can be replicated in other communities worldwide. A ethnobotany study in collaboration with these healers led to collection of 102 medicinal species from Itzama, their traditional healing cultural center and medicinal garden. Of these 102 species, 40 of prior reported 106 consensus study plants were present in the garden. There were 62 plants not previously reported growing in the garden as well. A general comparison of these plants was also made in relation to species reported in TRAMIL network, Caribbean Herbal Pharmacopoeia (CHP), the largest regional medicinal pharmacopoeia. A relative few species reported here were found in the CHP. However, the majority of the CHP plants are common in Belize and many are used by the nearby Mopan and Yucatec Maya. Since these 102 species are relied upon heavily in local primary healthcare, this Q’eqchi’ Maya medicinal garden represents possibilities toward novel sustainable, culturally relative holistic health promotion and community based conservation practices.
A Direct Road to Majorana Fields
Authors: Aste Andreas
Published: October 2010

A concise discussion of spin-1/2 field equations with a special focus on Majorana spinors is presented. The Majorana formalism which describes massive neutral fermions by the help of two-component or four-component spinors is of fundamental importance for the understanding of mathematical aspects of supersymmetric and other extensions of the Standard Model of particle physics, which may play an increasingly important role at the beginning of the LHC era. The interplay between the two-component and the four-component formalism is highlighted in an introductory way. Majorana particles are predicted both by grand unified theories, in which these particles are neutrinos, and by supersymmetric theories, in which they are photinos, gluinos and other states.
Toxin-Based Therapeutic Approaches
Authors: Shapira Assaf , Benhar Itai
Published: October 2010

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.
Warfarin Toxicity and Individual Variability—Clinical Case
Authors: Piatkov Irina , Rochester Colin , Jones Trudi , Boyages Steven
Published: October 2010

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives—superwarfarin anticoagulants—such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases.
De novo sequencing and development of EST‐SSR for Gevuina avellana (Proteaceae), a nut tree from South America
Authors: Riegel Ricardo , Diaz Leila , Véliz Débora
Published: October 2010

•Premise of the study: The aim of this study was to develop molecular tools to investigate the genetic structure and diversity of natural populations of Gevuina avellana (Molina, Proteaceae), the Chilean hazelnut. Simple sequence repeats (SSRs) derived from expressed sequence tags (EST‐SSRs) were developed, optimized, and characterized.

•Methods and Results: The microsatellite‐containing sequences were selected from a cDNA library developed from the nut. The eight marker loci showed two to seven alleles in 60 unrelated trees, from two different natural populations. The observed heterozygosity (Ho) was 0.44, ranging from 0.07 to 0.92 for different loci. When the multilocus genotype of the eight EST‐SSRs was considered, all trees could be differentiated.

•Conclusions: The newly identified EST‐SSRs in G. avellana and the multi‐pooling strategy involving eight markers will facilitate future studies of clone identification, genetic structure, and diversity.
Hydroxyurea Suppresses HCV Replication in Humans: A Phase I Trial of Oral Hydroxyurea in Chronic Hepatitis C Patients
Authors: Nozaki Akito , Numata Kazushi , Morimoto Manabu , Kondo Masaaki , Sugimori Kazuya , Morita Satoshi , Miyajima Eiji , Ikeda Masanori , Kato Nobuyuki , Maeda Shin , Tanaka Katsuaki
Published: October 2010

Background

HCV is the main causative agent of chronic liver disease, which could progress to liver cirrhosis and hepatocellular carcinoma. By using a recently developed genome-length HCV RNA replication reporter assay system, we found that hydroxyurea (HU), an inhibitor of DNA synthesis, inhibited HCV RNA replication.

Methods

To test the hypothesis that HU suppresses HCV replication in humans, we conducted a Phase I trial involving Japanese patients with chronic hepatitis C (CHC) and investigated the safety and effectiveness of a 4-week course of oral HU.

Results

A total of nine patients were treated with an HU dose level of 500 mg three times daily. Dose-limiting toxicity was not observed at this dose level. Of the nine patients, eight exhibited a moderate decrease in serum HCV RNA levels during the trial. A decrease in HCV RNA levels to nadir levels was achieved for the eight patients (median -0.27 log10 IU/ml [range -0.08– -0.44]) at various times during the 4 weeks after therapy initiation.

Conclusions

The results of this Phase I trial suggest that HU has potential as an anti-HCV agent that could be effective for the treatment of CHC patients.
Pharmacokinetics and safety of twice-daily atazanavir 300 mg and raltegravir 400 mg in healthy individuals
Authors: Zhu Li , Butterton Joan , Persson Anna , Stonier Michele , Comisar Wendy , Panebianco Deborah , Breidinger Sheila , Zhang Jenny , Bertz Richard
Published: October 2010

Background

Atazanavir plus raltegravir 300/400 mg twice daily is being explored as a ritonavir- and nucleoside- sparing treatment strategy. The pharmaco-kinetics and safety of this combination in healthy individuals were evaluated.

Methods

A total of 22 healthy individuals received raltegravir 400 mg on days 1–5, atazanavir 300 mg on days 6–12 and atazanavir plus raltegravir 300/400 mg on days 13–26, twice daily with a light meal. Serial blood samples were collected 12 h after the morning dose on days 5, 12 and 26; safety assessments, clinical laboratory data and serial electrocardiograms (ECGs) at 0, 2 and 6 h were obtained.

Results

Raltegravir coadministration reduced atazanavir geometric mean maximum plasma concentration (Cmax), area under the plasma concentration–time curve from 0 to 12 h post-dose (AUC0–12) and trough plasma concentration (Cmin) by 11%, 17% and 29%, respectively, compared with atazanavir alone. Geometric mean atazanavir Cmin was 817 ng/ml (range 250–1,550) with raltegravir coadministration. Atazanavir increased raltegravir geometric mean Cmax, AUC0–12 and Cmin by 39%, 54% and 48%, respectively. All adverse events were of mild or moderate intensity. Hyperbilirubinaemia and ECG PR increases with atazanavir were similar to those of atazanavir/ritonavir once daily. No corrected QT prolongations were noted. Mean QRS increase from baseline was 11.0 ms (range 2–25) after receiving atazanavir for 7 days; no further QRS increase was noted and no QRS interval was >120 ms with raltegravir coadministration. No ECG changes were observed with raltegravir alone.

Conclusions

Coadministration of atazanavir and raltegravir 300/400 mg twice daily decreased atazanavir AUC0–12 and Cmin relative to atazanavir alone, and increased AUC0–12 of raltegravir relative to raltegravir alone. Atazanavir and raltegravir alone and coadministered appeared safe and well-tolerated.
Effect of boosted fosamprenavir or lopinavir-based combinations on whole-body insulin sensitivity and lipids in treatment-naive HIV-type-1-positive men
Authors: Randell Paul A , Jackson Akil G , Boffito Marta , Back David J , Tjia John F , Taylor Jessica , Mandalia Sundhiya , Moyle Graeme J
Published: October 2010

Background

Antiretroviral therapy is associated with metabolic complications, including dyslipidaemia, body fat changes and insulin resistance. Healthy volunteer studies have demonstrated a decrease in glucose disposal associated with dosing with specific antiretrovirals.

Methods

HIV-type-1-positive male participants were randomized to receive tenofovir disoproxil fumarate and lamivudine, with either fosamprenavir (FPV)/ritonavir or lopinavir (LPV)/ritonavir twice daily. A hyperinsulinaemic euglycaemic clamp was performed at baseline and at 2 weeks after commencing treatment. The homeostasis model assessment index for insulin resistance (HOMA-IR) was also calculated at these time points. Changes in lipids and lipoprotein subfractions (by nuclear magnetic resonance spectroscopy) were assessed. A pharmacokinetic assessment was undertaken at week 2.

Results

A total of 27 participants were enrolled. There was no significant change in whole-body insulin sensitivity or HOMA-IR from baseline or between groups. Total cholesterol increased significantly, by 6.6% with FPV and 10.9% with LPV. The changes in lipids and lipoprotein subfractions were similar between groups with increases in triglycerides, very low-density lipoprotein (VLDL) and chylomicrons, and low-density lipoprotein (LDL) particles. Although the total high-density lipoprotein (HDL) particles were not significantly altered, a decrease in small HDL particles was seen. Changes in VLDL and chylomicron particles in both groups and triglycerides and small HDL particles in the LPV group were statistically significant.

Conclusions

In HIV-type-1-positive men initiating antiretroviral therapy with FPV- or LPV-based regimens, there were no significant changes in whole-body insulin sensitivity after 2 weeks. A proatherogenic lipid pro-file characterized by increases in triglycerides, VLDL and chylomicron particles and LDL particles, and a decrease in small HDL particles, was observed in both groups.
In Vitroandin VivoAnti-Influenza Virus Activity of Diarylheptanoids Isolated fromAlpinia Officinarum
Authors: Sawamura Rie , Shimizu Tomomi , Sun Yi , Yasukawa Ken , Miura Motofumi , Toriyama Masaharu , Motohashi Shigeyasu , Watanabe Wataru , Konno Katsuhiko , Kurokawa Masahiko
Published: October 2010

Background:

Diarylheptanoids (AO-0002 [7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-4 E-hepten-3-one] and AO-0011 [(5 S)-5-hydroxy-7-(4″-hydroxyphenyl)-1-phenyl-3-heptanone]) isolated from Alpinia officinarum have been reported to exhibit anti-influenza virus activity in vitro. Hence, efficacies against influenza virus infection and the mode of antiviral action were evaluated in vivo and in vitro, respectively.

Methods:

In a murine influenza virus infection model, diarylheptanoids were orally administered three times daily to mice infected with influenza A/PR/8/34 virus for 6 days after infection. AO-0002 was examined for its antiviral activity against the wild types of influenza viruses A/PR/8/34 (H1N1), oseltamivir-resistant A/PR/8/34 (H1N1), A/Bangkok/93/03 (H1N1), A/Ishikawa/7/82 (H3N2), A/Fukushima/13/43 (H3N2), B/Singapore/222/79 and B/Fukushima/15/93 in plaque reduction or yield reduction assays. The mode of anti-influenza virus action was assessed by a virus adsorption assay, immunofluorescence assay of viral antigens, and inhibition of viral messenger RNA synthesis using real-time reverse transcriptase PCR. Results: AO-0002 at 100 mg/kg was significantly effective in reducing the body weight loss and prolonging survival times of infected mice without toxicity, but AO-0011 was not. AO-0002 at 30 and 100 mg/kg significantly reduced virus titres in bronchoalveolar lavage fluids of the lungs on days 3 and 6 after infection. AO-0002 exhibited anti-influenza virus activity against all viruses used, including the oseltamivir-resistant strain in vitro. The compound had no effect on virus adsorption or invasion into cells, but dose-dependently suppressed the expression of viral messenger RNA and antigens.

Conclusions:

AO-0002 was suggested to have a different anti-influenza virus action to that of oseltamivir and was verified to show anti-influenza activity in vitro and in vivo.
Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside/ nucleotide analogue treatment among Chinese chronic hepatitis B patients
Authors: Yang Jing-Xian , Liu Bao-Ming , Li Xiao-Guang , Yan Chun-Hui , Xu Jie , Sun Xie-Wen , Wang Yu-Hua , Jiao Xiu-Juan , Yan Ling , Dong Jian-Ping , Hou Chun-Sheng , Abuduheilili Xiernayi , Li Tong , Zhuang Hui
Published: October 2010

Background

Antiviral drug-resistant HBV mutants under a variety of treatment protocols are complex and only partly understood. Here, a population-based cross-sectional study was performed to analyse the profile of resistance mutations in distinct evolutionary pathways refractory to different nucleoside/nucleotide analogues (NAs).

Methods

Serum samples of 199 chronic hepatitis B patients undergoing NA treatment from five hospitals in four northern cities of China were obtained between January 2007 and July 2009. The genotypic resistance of HBV in these samples was characterized. The full-length HBV reverse transcriptase region was amplified, sequenced and analysed with particular focus on the following NA-resistant changes: rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250.

Results

Among 199 HBV isolates, 30 (15.08%) and 169 (84.92%) were genotypes B and C, respectively, and 65 (32.66%) harboured NA-resistant mutations. The prevalence of mutations at rtM204 was 34.33% in 134 patients who had received or who had been exposed to lamivudine-based therapy. Five cases of rtN236 mutations were detected exclusively among 75 patients receiving adefovir-dipivoxil-based therapies. A total of 19 cases of multidrug resistance rtA181 mutations were observed in those with lamivudine-, adefovir-dipivoxil- or telbivudine-based treatment (186 cases), but not in those undergoing entecavir treatment (13 cases). Mutations were not found at rtI169, rtT184, rtA194 or rtS202. rtM204 mutations (27 rtM204I, 15 rtM204V and 5 rtM204I/V cases) were detected at the highest frequency among 65 mutants (72.30% [47/65]) and found to display 16 combination mutation patterns, in which rtM204I and rtM204V were significantly associated with rtL80I/V and rtL180M, respectively ( P<0.01).

Conclusions

One-third of the studied population harboured NA-resistant HBV with complicated mutation patterns. Monitoring HBV genotypic resistance mutation markers and patterns is therefore shown to be beneficial for optimizing antiviral therapies and for avoiding clinical deterioration.
Evolution and suppression of HBV strains with multidrug resistance to lamivudine, adefovir dipivoxil and entecavir in a patient with chronic hepatitis B
Authors: Liu Yan , Wang Chunmei , Zhong Yanwei , Chen Li , Li Xiaodong , Ji Dong , Wang Huifen , Xin Shaojie , Zoulim Fabien , Xu Dongping
Published: October 2010

Here, we report a case of multidrug resistance in a patient with chronic hepatitis B. The patient sequentially received lamivudine, adefovir dipivoxil and entecavir, and subsequently developed single-, double- and triple-drug-resistant HBV strains. We consider this case report important because it documents, for the first time, that triple-drug-resistant HBV strains identified in a clinical setting were suppressible by lamivudine add-on adefovir dipivoxil when tenofovir disoproxil fumarate was not available.
Nano-NRTIs: Efficient Inhibitors of HIV Type-1 in Macrophages with a Reduced Mitochondrial Toxicity
Authors: Vinogradov Serguei V , Poluektova Larisa Y , Makarov Edward , Gerson Trevor , Senanayake Madapathage T
Published: October 2010

Background:

Macrophages serve as a depot for HIV type-1 (HIV-1) in the central nervous system. To efficiently target macrophages, we developed nanocarriers for potential brain delivery of activated nucleoside reverse transcriptase inhibitors (NRTIs) called nano-NRTIs.

Methods:

Nanogel carriers consisting of poly(ethylene glycol) (PEG)- or Pluronic-polyethylenimine (PEI) biodegradable networks, star PEG-PEI or poly(amidoamine) dendrimer-PEI-PEG dendritic networks, as well as nanogels decorated with brain-targeting peptide molecules, specifically binding to the apolipoprotein E receptor, were synthesized and evaluated. Nano-NRTIs were obtained by mixing aqueous solutions of zidovudine 5′-triphosphate or didanosine 5′-triphosphate and nanocarriers, followed by freeze-drying. Intracellular accumulation, cytotoxicity and antiviral activity of nano-NRTIs were monitored in monocyte-derived macrophages (MDMs). HIV-1 viral activity in infected MDMs was measured by a reverse transcriptase activity assay following treatment with nano-NRTIs. Mitochondrial DNA depletion in MDMs and human HepG2 cells was assessed by quantitative PCR.

Results:

Nanogels were efficiently captured by MDMs and demonstrated low cytotoxicity, and no antiviral activity without drugs. All nano-NRTIs demonstrated high efficacy of HIV-1 inhibition at drug levels as low as 1 μmol/l, representing a 4.9- to 14-fold decrease in 90% effective drug concentrations as compared with NRTIs, whereas 50% cytotoxicity effects started at 200x higher concentrations. Nano-NRTIs with a core-shell structure and decorated with brain-targeting peptides displayed the highest antiviral efficacy. Mitochondrial DNA depletion, a major cause of NRTI neurotoxicity, was reduced threefold compared with NRTIs at application of selected nano-NRTIs.

Conclusions:

Nano-NRTIs demonstrated a promising antiviral efficacy against HIV-1 in MDMs and showed strong potential as nanocarriers for delivery of antiviral drugs to macrophages harbouring in the brain.
Temps professionnels et familiaux en Europe : de nouvelles configurations
Authors: Silvera Rachel
Published: October 2010

Résumé Mieux articuler les temps professionnels et familiaux est un des thèmes majeurs des politiques européennes, qui défendent ainsi le principe fondamental d’égalité entre les femmes et les hommes, mais aussi des objectifs économiques et démographiques : permettre aux femmes d’être plus nombreuses sur le marché du travail tout en facilitant leur rôle de mères et leur capacité à prodiguer les soins à autrui. L’objectif de cet article est de dresser dans un premier temps un panorama actualisé mais incomplet des dispositifs publics d’articulation des temps en Europe (temps, services, dépenses publiques) et dans un second temps, d’observer ce qui relève de la responsabilité d’autres acteurs en dehors de l’Etat, comme l’entreprise. Ceci nous amènera à retracer l’évolution des modèles européens en matière de « conciliation », selon le rôle de l’Etat, du marché et de la famille. Au-delà des discours, les pratiques sont loin d’être homogènes et ne semblent pas converger vers ce projet commun de « conciliation » et d’égalité soutenu pourtant par les politiques de l’Union européenne.
Politiques familiales contre politiques de l'égalité des sexes ? Le cas de l'Allemagne
Authors: Veil Mechthild
Published: October 2010

Résumé En Allemagne, aujourd’hui, on assiste à une modernisation de la politique familiale, jusqu’alors conservatrice, en vue d’un rattrapage vis-à-vis de la France et de l’Union Européenne. Les deux réformes emblématiques de ce changement sont d’une part l’extension des structures d’accueil de la petite enfance et d’autre part la réforme d’allocation parentale. Cet article vise l’analyse de ces mesures sous différents angles : tout d’abord, il s’agit d’établir une corrélation éventuelle entre les politiques familiales et l’égalité des sexes ; par ailleurs, on observe les transformations en œuvre dans la fameuse « conciliation » à l’allemande ; enfin, on relève les incidences de ces dispositifs sur la natalité, particulièrement basse, notamment chez les personnes qualifiées (dont les universitaires). Les résultats sont mitigés : du côté positif, on peut considérer que la « conciliation » répond davantage aux besoins des mères actives et renforce le rôle des hommes en tant que pères. Mais d’un point de vue plus négatif, on constate une sélectivité des stratégies d’égalité entre les femmes et les hommes, focalisées sur les ménages aisés et bi-actifs, masquant ainsi les inégalités sociales. Finalement, les différents modèles – celui de la mère active qui va de pair avec celui du père « breadwinner » – coexistent de façon conflictuelle. Désormais, « l’indétermination normative » crée une brèche dans le concept d’égalité entre les femmes et les hommes.
Antiféminisme et féminisme élitiste en Allemagne : les termes du débat
Authors: Klaus Elisabeth
Published: October 2010

Résumé Longtemps stigmatisé dans le discours social en Allemagne, le féminisme a récemment connu un renouveau : il a été utilisé dans des contextes politiques jusqu’alors inhabituels et en relation avec de nouvelles positions idéologiques. Le nouveau débat féministe fut promu par une célèbre ex-présentatrice du journal télévisé quand elle publia un bestseller accusant le féminisme de presque tous les maux sociaux auxquels la société allemande est confrontée aujourd’hui. L’article révèle des indicateurs du fait que l’attaque d’Eva Hermann contre les mouvements féministes des années 70 n’est qu’une partie d’un vaste réseau anti-féministe organisé efficacement et qui utilise la nouvelle technologie des media à son avantage. De nombreuses voix de protestation se sont élevées contre les opinions très traditionnelles de l’ancienne présentatrice. Les media ont apposé le label passe-partout de « nouveau féminisme » sur ces voix. Toutefois, un examen plus attentif de la non-fiction la plus populaire publiée dans ce contexte révèle un fort conservatisme qui se rapproche dangereusement des, et parfois touche les positions antiféministes. Il y est affirmé que « le féminisme conservateur » a quatre caractéristiques : la distanciation avec un féminisme plus ancien et sans doute dépassé ; l’auto-célébration néolibérale ; l’absence d’analyse critique sociale ; une orientation sexuelle invariablement hétérosexuelle.
Typhlocharis algarvensis Coiffait, 1971: redescripción y afinidades (Coleoptera, Caraboidea, Trechidae)
Authors: Zaballos J. P. , Pérez González S.
Published: October 2010

Se actualiza la descripción de Typhlocharis algarvensis Coiffait, 1971 incluyendo caracteres desconocidos para la especie como la genitalia masculina y femenina, pars stridens, dimorfismo sexual, pelo mesotibial y ojales de los élitros. Se discuten las afinidades taxonómicas de la especie y el valor taxonómico de la serie umbilicada de los élitros y la forma de los gonocoxitos a la hora de establecer los grupos de especies en el género.
Bathyodontus mirus (Andrássy, 1956), primera cita de un representante del suborden Bathyodontina (Nematoda, Mononchida) en la fauna ibérica
Authors: Abolafia J. , Peña-Santiago R.
Published: October 2010

Se estudia la especie Bathyodontus mirus (Andrássy, 1956) Hopper y Cairns, 1956, recolectada en dunas de arena en el suroeste peninsular. Se presentan una descripción, medidas e ilustraciones (fotografías con microscopía óptica). Los ejemplares ibéricos se comparan brevemente con otras poblaciones conocidas de la misma especie. Y se ofrece un compendio de las especies del género Bathyodontus, incluida una clave para su identification. Se trata de la primera cita de un miembro del suborden Bathyodontina en el ámbito Ibero-balear y en la región Mediterránea.
CCR2 Identifies a Stable Population of Human Effector Memory CD4+ T Cells Equipped for Rapid Recall Response
Authors: Zhang Hongwei H. , Song Kaimei , Rabin Ronald L. , Hill Brenna J. , Perfetto Stephen P. , Roederer Mario , Douek Daniel C. , Siegel Richard M. , Farber Joshua M.
Published: October 2010

Because T cells act primarily through short-distance interactions, homing receptors can identify colocalizing cells that serve common functions. Expression patterns for multiple chemokine receptors on CD4+ T cells from human blood suggested a hierarchy of receptors that are induced and accumulate during effector/memory cell differentiation. We characterized CD4+CD45RO+ T cells based on expression of two of these receptors, CCR5 and CCR2, the principal subsets being CCR5−CCR2− (∼70%), CCR5+CCR2− (∼25%), and CCR5+CCR2+ (∼5%). Relationships among expression of CCR5 and CCR2 and CD62L, and the subsets’ proliferation histories, suggested a pathway of progressive effector/memory differentiation from the CCR5−CCR2− to CCR5+CCR2− to CCR5+CCR2+ cells. Sensitivity and rapidity of TCR-mediated activation, TCR signaling, and effector cytokine production by the subsets were consistent with such a pathway. The subsets also showed increasing responsiveness to IL-7, and the CCR5+CCR2+ cells were CD127bright and invariably showed the greatest response to tetanus toxoid. CCR5+CCR2+ cells also expressed the largest repertoire of chemokine receptors and migrated to the greatest number of chemokines. By contrast, the CCR5+CCR2− cells had the greatest percentages of regulatory T cells, activated/cycling cells, and CMV-reactive cells, and were most susceptible to apoptosis. Our results indicate that increasing memory cell differentiation can be uncoupled from susceptibility to death, and is associated with an increase in chemokine responsiveness, suggesting that vaccination (or infection) can produce a stable population of effector-capable memory cells that are highly enriched in the CCR5+CCR2+ subset and ideally equipped for rapid recall responses in tissue.
Drug Antigenicity, Immunogenicity, and Costimulatory Signaling: Evidence for Formation of a Functional Antigen through Immune Cell Metabolism
Authors: Elsheikh Ayman , Lavergne Sidonie N. , Castrejon J. Luis , Farrell John , Wang Haiyi , Sathish Jean , Pichler Werner J. , Park B. Kevin , Naisbitt Dean J.
Published: October 2010

Recognition of drugs by immune cells is usually explained by the hapten model, which states that endogenous metabolites bind irreversibly to protein to stimulate immune cells. Synthetic metabolites interact directly with protein-generating antigenic determinants for T cells; however, experimental evidence relating intracellular metabolism in immune cells and the generation of physiologically relevant Ags to functional immune responses is lacking. The aim of this study was to develop an integrated approach using animal and human experimental systems to characterize sulfamethoxazole (SMX) metabolism-derived antigenic protein adduct formation in immune cells and define the relationship among adduct formation, cell death, costimulatory signaling, and stimulation of a T cell response. Formation of SMX-derived adducts in APCs was dose and time dependent, detectable at nontoxic concentrations, and dependent on drug-metabolizing enzyme activity. Adduct formation above a threshold induced necrotic cell death, dendritic cell costimulatory molecule expression, and cytokine secretion. APCs cultured with SMX for 16 h, the time needed for drug metabolism, stimulated T cells from sensitized mice and lymphocytes and T cell clones from allergic patients. Enzyme inhibition decreased SMX-derived protein adduct formation and the T cell response. Dendritic cells cultured with SMX and adoptively transferred to recipient mice initiated an immune response; however, T cells were stimulated with adducts derived from SMX metabolism in APCs, not the parent drug. This study shows that APCs metabolize SMX; subsequent protein binding generates a functional T cell Ag. Adduct formation above a threshold stimulates cell death, which provides a maturation signal for dendritic cells.
T Cell Polarity at the Immunological Synapse Is Required for CD154-Dependent IL-12 Secretion by Dendritic Cells
Authors: Tourret Marie , Guégan Sarah , Chemin Karine , Dogniaux Stéphanie , Miro Francesc , Bohineust Armelle , Hivroz Claire
Published: October 2010

Ag-specific interaction between T lymphocytes and dendritic cells (DCs) leads to both T cell and DC activation. CD154 (CD40 ligand)/CD40 interactions have been shown to play a major, although not exclusive, role in this functional cross-talk. Interactions between T cells and DCs are structured by an immunological synapse (IS), characterized by polarization of the T cell microtubule cytoskeleton toward the interacting DCs. Yet the role T cell polarization may play in T cell-induced DC activation is mostly unknown. In this study, we address the role of T cell polarity in CD154-dependent activation of DCs in a human model, using two different tools to block T cell polarity (i.e., a microtubule depolymerizing drug and an inhibitor of atypical protein kinase C). We show that CD154 is recruited and concentrated at the IS formed between human primary T cells and autologous DCs and that this recruitment requires T cell polarity at the IS. Moreover, we show that T cell polarization at the IS controls T cell-dependent CD154–CD40 signaling in DCs as well as CD154-dependent IL-12 secretion by DCs. This study shows that T cell polarity at the IS plays a key role in CD154/CD40-dependent cross-talk between CD4+ T cells and DCs.
Umbilical Cord-Derived Mesenchymal Stromal Cells Modulate Monocyte Function to Suppress T Cell Proliferation
Authors: Cutler Antony J. , Limbani Vasanti , Girdlestone John , Navarrete Cristina V.
Published: October 2010

Mesenchymal stromal cells (MSCs) may be derived from a variety of tissues, with human umbilical cord (UC) providing an abundant and noninvasive source. Human UC-MSCs share similar in vitro immunosuppressive properties as MSCs obtained from bone marrow and cord blood. However, the mechanisms and cellular interactions used by MSCs to control immune responses remain to be fully elucidated. In this paper, we report that suppression of mitogen-induced T cell proliferation by human UC-, bone marrow-, and cord blood-MSCs required monocytes. Removal of monocytes but not B cells from human adult PBMCs (PBMNCs) reduced the immunosuppressive effects of MSCs on T cell proliferation. There was rapid modulation of a number of cell surface molecules on monocytes when PBMCs or alloantigen-activated PBMNCs were cultured with UC-MSCs. Indomethacin treatment significantly inhibited the ability of UC-MSCs to suppress T cell proliferation, indicating an important role for PGE2. Monocytes purified from UC-MSC coculture had significantly reduced accessory cell and allostimulatory function when tested in subsequent T cell proliferation assays, an effect mediated in part by UC-MSC PGE2 production and enhanced by PBMNC alloactivation. Therefore, we identify monocytes as an essential intermediary through which UC-MSCs mediate their suppressive effects on T cell proliferation.
Elevated Levels of Soluble TNF Receptors 1 and 2 Correlate with Plasmodium falciparum Parasitemia in Pregnant Women: Potential Markers for Malaria-Associated Inflammation
Authors: Thévenon Audrey Davidson , Zhou James A. , Megnekou Rosette , Ako Simon , Leke Rose G. F. , Taylor Diane Wallace
Published: October 2010

Plasmodium falciparum-infected erythrocytes (IEs) sequester in the intervillous space (IVS) of the placenta causing placental malaria (PM), a condition that increases a woman’s chances of having a low-birth-weight baby. Because IEs sequester, they frequently are not observed in peripheral blood smears, resulting in women with PM being misdiagnosed and thus not treated. Because sequestered IEs induce inflammation in the IVS, detection of inflammatory mediators in the peripheral blood may provide an approach for diagnosing PM. Two counterregulatory molecules, TNF-αR (TNFR) 1 and TNFR2, modulate the pathological effects of TNF-α. Levels of these soluble TNFRs (sTNFRs) are reported to be elevated in children with severe malaria, but it is unclear if they are increased in the peripheral blood of PM-positive women with asymptomatic infections. In this study, sTNFR levels were measured throughout the course of pregnancy, as well as at delivery, in women with asymptomatic infections and those who remained uninfected. Results showed that both sTNFRs were significantly increased in the peripheral blood of women with asymptomatic malaria (p < 0.0001) and were positively correlated with parasitemia (p < 0.0001 for sTNFR1 and p = 0.0046 for sTNFR2). Importantly, levels of sTNFR2 were elevated in the peripheral blood of women who were PM-positive but peripheral blood-smear negative (p = 0.0017). Additionally, sTNFR2 levels were elevated in the blood of malaria-positive women who delivered low-birth-weight babies. In vitro studies demonstrated that syncytiotrophoblasts were not a major source of sTNFR. These data suggest that sTNFR2 may be a valuable biomarker for detection of malaria-associated inflammation.