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21 avril 2011 4 21 /04 /avril /2011 16:46





Pioneering surgeon Susan Lim performed the first liver transplant in Asia. But a moral concern with transplants (where do donor livers come from ...) led her to look further, and to ask:

Could we be transplanting cells, not whole organs? At the INK Conference, she talks through her new research, discovering healing cells in some surprising places.


Susan Lim established her reputation as a surgeon in 1990 after performing Singapore's (and southeast Asia's) first successful liver transplant.

She has gone on to further pioneer in the field of general surgery, two new surgical technologies for Singapore, the mammotome minimally invasive breast biopsy and robotic surgery for the private sector.

She founded and is chair and CEO of Centre for Robotic Surgery and spearheaded the Robotic General Surgery Program for Singapore.

In 2003, Dr. Lim launched Stem Cell Technologies (i), a biotech company to research the use of adult stem cells for application in cell therapy and regenerative medicine. In 2004, SCT(i) entered into research collaboration with National University of Singapore to specifically research the use of adult stem cells as a treatment for diabetes.

In 2008, the American Academy of Continuing Medical Education named its 28th award the Dr. Susan Lim Award, in honour of Dr. Lim's career, contribution and international achievement.

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20 avril 2011 3 20 /04 /avril /2011 12:02

J Cell Sci. 2011 Apr 1;124(Pt 7):1043-54. Epub 2011 Mar 1.

Nitric oxide is the primary mediator of cytotoxicity induced by GSH depletion in neuronal cells.

Aquilano KBaldelli SCardaci SRotilio GCiriolo MR.

Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.


Glutathione (GSH) levels progressively decline during aging and in neurodegenerative disorders.


However, the contribution of such event in mediating neuronal cell death is still uncertain. In this report, we show that, in neuroblastoma cells as well as in primary mouse cortical neurons, GSH decrease, induced by buthionine sulfoximine (BSO), causes protein nitration, S-nitrosylation and DNA strand breaks.


Such alterations are also associated with inhibition of cytochrome c oxidase activity and microtubule network disassembly, which are considered hallmarks of nitric oxide (NO) toxicity.


In neuroblastoma cells, BSO treatment also induces cell proliferation arrest through the ERK1/2-p53 pathway that finally results in caspase-independent apoptosis, as evident from the translocation of apoptosis-inducing factor from mitochondria towards nuclei.


A deeper analysis of the signaling processes indicates that the NO-cGMP pathway is involved in cell proliferation arrest and death. In fact, these events are completely reversed by L-NAME, a specific NO synthase inhibitor, indicating that NO, rather than the depletion of GSH per se, is the primary mediator of cell damage.


In addition, the guanylate cyclase (GC) inhibitor LY83583 is able to completely block activation of ERK1/2 and counteract BSO toxicity. In cortical neurons, NMDA (N-methyl-D-aspartic acid) treatment results in GSH decrease and BSO-mediated NO cytotoxicity is enhanced by either epidermal growth factor (EGF) or NMDA.


These findings support the idea that GSH might represent the most important buffer of NO toxicity in neuronal cells, and indicate that the disruption of cellular redox buffering controlled by GSH makes neuronal cells susceptible to endogenous physiological flux of NO.


PMID: 21363890 [PubMed - in process]

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20 avril 2011 3 20 /04 /avril /2011 11:57

Toxicology. 2011 Mar 23. [Epub ahead of print]

Advances in metal-induced oxidative stress and human disease.

Jomova KValko M.

Department of Chemistry, Faculty of Natural Sciences, Constantine The Philosopher University, SK-949 74 Nitra, Slovakia.

Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems.


Disruption of metal ion homeostasis may lead to oxidative stress,

a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently

induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases,

involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others.


The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts.


On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione.


Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed.

A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress.

It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms.

In addition, Zn has an impact on the immune system and possesses neuroprotective properties.

The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants.

Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, and other antioxidants) are capable of chelating metal ions reducing thus their catalytic acitivity to form ROS.


A novel therapeutic approach to supress oxidative stress is based on the development of dual function antioxidants comprising not only chelating, but also scavenging components.


Parodoxically, two major antioxidant enzymes, superoxide dismutase (SOD) and catalase contain as an integral part of their active sites metal ions to battle against toxic effects of metal-induced free radicals.


The aim of this review is to provide an overview of redox and non-redox metal-induced formation of free radicals and the role of oxidative stress in toxic action of metals.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID: 21414382 [PubMed - as supplied by publisher]


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20 avril 2011 3 20 /04 /avril /2011 11:53


J Toxicol Sci. 2011;36(2):231-5.

Glutathione depression by dihydropyrazine derivative.

Takechi SIto SKashige NIshida TYamaguchi T.

Faculty of Pharmaceutical Sciences, Sojo University.

Dihydropyrazine (DHP), which is formed by nonenzymatic glycation, generates various radical species that lead to DNA damage and enzyme inhibition.


In this study, we examined the reaction between DHP derivatives and glutathione (GSH).


DHP exposure caused more intense growth inhibition of a GSH-deficient mutant Escherichia coli strain compared with the wild-type strain.


DHP-exposed mouse fibroblasts showed a decrease in the cellular GSH level.


The obtained data suggested that the reaction of DHP with GSH possibly potentiates cellular stress via the depletion of cellular GSH levels.

PMID: 21467750 [PubMed - in process]


La dihydropyridine ou dihydroazine est un composé organique dérivé de la pyridine. Elle est en effet constituée d'une hétérocycle à 6 atomes dont un atome d'azote (et 5 de carbone) mais seulement partiellement insaturé, avec seulement deux liaisons doubles (contre 3 pour la pyridine).

Les dérivés de la dihydropyridine sont simplement appelés dihydropyridines, et sont une classe de médicaments antagonistes du calcium; elles sont utilisées dans le traitement de l'hypertension artérielle et de l'angine de poitrine.

Mode d'actionMédicaments

Les dihydropyridines bloquent l'influx des ions calcium dans les cellules musculaires lisses des artères coronaires et périphériques, empêchant ainsi la contraction de ces vaisseaux. Elles sont ainsi utilisées en tant qu'hypotenseur.

Effets indésirables

Les effets indésirables les plus fréquents de cette classe de médicaments sont:

Des effets hépatiques et des syndromes parkinsoniens2 ont également été observés.

Principes actifs de cette classe[

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20 avril 2011 3 20 /04 /avril /2011 11:42

J Neurosci Res. 2011 Apr 12. doi: 10.1002/jnr.22630. [Epub ahead of print]

Vitamin K has the potential to protect neurons from methylmercury-induced cell death In Vitro.

Sakaue MMori NOkazaki MKadowaki EKaneko THemmi NSekiguchi HMaki TOzawa AHara SArishima KYamamoto M.

Department of Anatomy II, School of Veterinary Medicine, Azabu University, Sagamihara, Japan; Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. sakaue@azabu-u.ac.jp.

Vitamin K (VK) has a protective effect on neural cells.

Methylmercury is a neurotoxicant that directly induces neuronal death in vivo and in vitro.

Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury.


To prove our hypothesis in vitro, we investigated the protective effects of VKs (phylloquinone, vitamin K(1) ; menaquinone-4, vitamin K(2) ) on methylmercury-induced death in primary cultured neurons from the cerebella of rat pups.

As expected, VKs inhibited the death of the primary cultured neurons.

It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH).

Actually, treatment with GSH and a GSH inducer, N-acetyl cysteine, inhibited methylmercury-induced neuronal death in the present study.


Thus, we investigated whether VKs also have protective effects against GSH-depletion-induced cell death by employing two GSH reducers, L-buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR-32 cells.


Treatment with VKs affected BSO- and DEM-induced cell death in both cultures.


On the other hand, the intracellular GSH assay showed that VK(2) , menaquinone-4, did not restore the reduced GSH amount induced by methylmercury or BSO treatments.


These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels.


The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion. 

PMID: 21488088 [PubMed - as supplied by publisher]

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20 avril 2011 3 20 /04 /avril /2011 09:29

Journal of Exposure Science and Environmental Epidemiology (2011) 21, 328–335; doi:10.1038/jes.2010.33; published online 26 May 2010

Comparison of a toxicokinetic and a questionnaire-based approach to assess methylmercury intake in exposed individuals

Nolwenn Noisela, Michèle Boucharda, Gaétan Carriera and Michel Planteb

  1. aDepartment of Environmental and Occupational Health, Faculty of Medicine, Université de Montréal, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada
  2. bHydro-Québec, Health and Safety Division, 75 boulevard René-Lévesque West, Montreal, Quebec H2Z 1A4, Canada

Correspondence: Professor Michèle Bouchard, Department of Environmental and Occupational Health, Faculty of Medicine, Université de Montréal, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada. Tel: +514 343 6111 ext 1640; Fax: +514 343 2200; E-mail: michele.bouchard@umontreal.ca

Received 7 January 2010; Accepted 16 April 2010; Published online 26 May 2010.

Methylmercury (MeHg) is a neurotoxic contaminant and one of the main sources of exposure in humans is seafood consumption.

It is thus of interest to assess precisely MeHg exposure.

The objective of this study was to estimate MeHg daily intake in exposed individuals using two different approaches, a food questionnaire and toxicokinetic modeling, and compare the complementary and use of each method.

For this purpose, a group of 23 fishermen from northern Quebec provided blood and hair samples and answered a standard food questionnaire focusing on seafood consumption.

A published and validated toxicokinetic model was then used to reconstruct MeHg daily intakes from mercury (Hg) measurements in biological samples.

These intakes were compared to those estimated using a standard food questionnaire on seafood consumption.

Daily intakes of MeHg from seafood (mean/median (range)) estimated from hair concentrations with the toxicokinetic-based approach were 6.1/5.2 (0.0–19) μg/day.

These intake values were on average six times lower than those estimated using a food questionnaire, that is, 49/32 (7.2–163)μg/day.

No correlation was found between the toxicokinetic-based and the questionnaire estimates of MeHg daily intakes.

Most of the MeHg intakes estimated with the food questionnaire (21/23) exceeded the US EPA RfD of 0.1μg/kg bw/day, whereas only a small proportion (6/23) of modeled estimates exceeded the RfD.

This study shows that human health risk estimates strongly depend on the chosen approach.


methylmercury; toxicokinetic modeling; food questionnaire; daily intake; seafood consumption; biomarker


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20 avril 2011 3 20 /04 /avril /2011 09:24

ublished online 10 March 2010

Parabens in urine, serum and seminal plasma from healthy Danish men determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS)

Hanne Frederiksena, Niels Jørgensena and Anna-Maria Anderssona

aDepartment of Growth and Reproduction, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

Correspondence: Dr. Hanne Frederiksen, Department of Growth and Reproduction, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen DK-2100, Denmark. Tel.: +45 3545 9592. Fax: +45 3545 6054. E-mail: hanne.01.frederiksen@rh.regionh.dk

Received 6 October 2009; Accepted 24 January 2010; Published online 10 March 2010.


Parabens are used as anti-microbial preservatives in a range of consumer products, especially in cosmetics. In vitro and animal studies have shown weak estrogenic and other endocrine disrupting effects of parabens, including reduced testosterone levels in exposed male rats.

The knowledge of paraben exposure, distribution and excretion in humans is limited. In this study we determined the concentration of five parabens; methyl-, ethyl-, n-propyl-, n-butyl- and benzylparaben in urine, serum and seminal plasma samples from 60 healthy Danish men.

To conduct the study a sensitive and specific method using LC–MS/MS for simultaneous determination of the five parabens was developed for all three different matrices.

Highest concentrations of the parabens were found in urine, wherein methyl-, ethyl-, n-propyl- and n-butyl parabens were measurable in 98%, 80%, 98% and 83% of the men, respectively.

Benzyl paraben was only measurable in urine from 7% of the men.

Methyl- and n-propyl parabens were also measurable in the majority of serum and seminal plasma samples, whereas the other parabens could only be detected in some of the samples.

In all the three matrices significant correlations between the parabens were seen. Furthermore, urinary paraben concentrations correlate to the paraben concentrations in both serum and seminal plasma.


endocrine disruptor; paraben; human urine; human serum; seminal plasma; LC–MS/MS

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20 avril 2011 3 20 /04 /avril /2011 09:18

Journal of Exposure Science and Environmental Epidemiology (2011) 21, 224–233; doi:10.1038/jes.2010.2; published online 3 March 2010

Internal exposure to pollutants and sexual maturation in Flemish adolescents

Elly Den Honda, Willem Dhoogeb, Liesbeth Bruckersc, Greet Schoetersa,d, Vera Nelene, Els van de Mieroope, Gudrun Koppena, Maaike Bilauf, Carmen Schroijeng, Hans Keuneh, Willy Baeyensg and Nicolas van Larebekei

.                aFlemish Institute of Technological Research, Environmental Risk and Health, Boeretang 200, B-2400 Mol, Belgium

.                bDepartment of Endocrinology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium

.                cInteruniversity Institute for Biostatistics and statistical Bioinformatics, University of Hasselt, Agoralaan 1, B-3590 Diepenbeek, Belgium

.                dDepartment of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium

.                eProvincial Institute of Hygiene, Kronenburgstraat 45, B-2000 Antwerp, Belgium

.                fDepartment of Public Health, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium

.                gDepartment of Analytical and Environmental Chemistry (ANCH), Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium

.                hFaculty of Political and Social Sciences, University of Antwerp, Antwerp, Belgium

.                iDepartment of Radiotherapy, Nuclear Medicine and Experimental Cancerology, Study Centre for Carcinogenesis and Primary Prevention of Cancer, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium

Correspondence: Dr E Den Hond, Flemish Institute of Technological Research (Vito), Environmental Risk and Health, Boeretang 200, B-2400 Mol, Belgium. Tel.: + 32 14 33.52.28. Fax: + 32 14 58.26.57. E-mail: elly.denhond@vito.be

Received 31 July 2009; Accepted 13 January 2010; Published online 3 March 2010.


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Flanders is densely populated with much industry and intensive farming.

Sexual maturation of adolescents (aged 14–15 years) was studied in relation to internal exposure to pollutants.

Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas.

Data on sexual development were obtained from the medical school examination files.

Self-assessment questionnaires provided information on health, use of medication and lifestyle factors.

In boys, serum levels of hexachlorobenzene (HCB), p,p′-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development).

Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia.

In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche.

Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development.

However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.

Keywords: PCBs; pesticides; metals; endocrine disruptors; biomonitoring

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19 avril 2011 2 19 /04 /avril /2011 18:38

Medicina (Kaunas). 2009;45(12):992-9.

Phenolics and anthocyanins in berries of European cranberry and their antimicrobial activity.

Cesoniene LJasutiene ISarkinas A.

Kaunas Botanical Garden, Vytautas Magnus University, Z. E. Zilibero 6, 46324 Kaunas, Lithuania. l.cesoniene@bs.vdu.lt

European cranberry is a berry plant rich in biologically active substances, making it valued by both the phyto-pharmaceutical and food industries. The aim of this study was to examine the accumulation of phenolic compounds and anthocyanins in berries of European cranberry and to assess their antibacterial activity.


MATERIAL AND METHODS: Different wild clones of European cranberry were investigated according to berry weight and the amounts of total phenolics and anthocyanins. Anthocyanin profiles of extracts were evaluated by HPLC, whereas the antimicrobial properties were determined by the agar well diffusion method. A strong negative correlation between berry weight and the amount of anthocyanins was found. The amount of total phenolics among different cranberry clones in the field collection ranged from 224.0 mg/100 g to 498.0 mg/100 g, and the amount of total anthocyanins ranged from 40.7 mg/100 g to 207.3 mg/100 g. Quantitative HPLC-UV analysis revealed six anthocyanins in the berries of European cranberry, among which the anthocyanin peonidin-3-galactoside was most prevalent.


CONCLUSIONS: Investigation of the antimicrobial properties showed that European cranberry extracts inhibited the growth of wide range of human pathogenic bacteria, both gram-negative (Escherichia coli and Salmonella typhimurium) and gram-positive (Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Bacillus subtilis).

PMID: 20173403 [PubMed - indexed for MEDLINE]

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19 avril 2011 2 19 /04 /avril /2011 18:36

Phytother Res. 2011 Jan;25(1):122-7. doi: 10.1002/ptr.3240.

Inhibition activity of wild berry juice fractions against Streptococcus pneumoniae binding to human bronchial cells.

Huttunen SToivanen MArkko SRuponen MTikkanen-Kaukanen C.

Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland. sanna.huttunen@uef.fi


Bacterial adhesion to the cell surface is a crucial step before infection can take place. Inhibition of bacterial binding offers a novel preventive approach against infections. Cranberry (Vaccinium macrocarpon Ait.) juice has been found to have antiadhesive activity against different bacteria.


Streptococcus pneumoniae is an important pathogen and the most common cause for pneumonia, meningitis, and otitis media. In this study the inhibitory activity of cranberry (Vaccinium oxycoccos L.), bilberry (Vaccinium myrtillus L.) and crowberry (Empetrum nigrum and Empetrum hermaphroditum L.) juice fractions against pneumococcal binding was tested using human bronchial cells (Calu-3) as an adhesion model. In addition, the antimicrobial activity of the berry juice fractions was tested. It was found that the studied berry juice fractions had antiadhesion activity and cranberry juice was the most active.


The adhesion inhibition activity of cranberry juice was nearly 90% at a concentration of 8.7 mg/g of soluble solids. The antimicrobial activity of the studied berry juice fractions was found to be remarkable; pneumococcal growth was inhibited totally at a concentration of ∼86 mg/g.


Both antiadhesion and antimicrobial activities were reduced after solid-phase extraction of the berry juices, which may suggest molecular synergistic effects of the berry juice molecules against S. pneumoniae.


The findings indicate that cranberry, bilberry and crowberry juices have potential against pneumococcal infections.



Copyright © 2010 John Wiley & Sons, Ltd.

PMID: 20625989 [PubMed - in process]

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