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Month: May 2013

Physicians insufficiently informed of the side effects of drugs.

Posted on by Priscille Rivière

An international study involving 255 physicians practising in Vancouver, Montreal, Sacramento and Toulouse found that physicians are not given enough information about the adverse effects of drugs during presentations made by medical sales representatives from pharmaceutical companies. And yet, these same physicians are willing to prescribe at least some of the presented drugs. Dr. Geneviève Durrieu (from the Pharmaco-epidemiology team assessing the use of medication and the risks involved, Unit 1027 “Epidemiology and public health analyses: risks, chronic diseases and handicaps” – Inserm / Université Toulouse III – Paul Sabatier) led the French part of this study, the results of which are published in the Journal of General Internal Medicine. Within the framework of this international study, is France proving to be a model student?

boites de médicaments

©Fotolia

Prescription-only drugs play a major part in the therapeutic care of the patient. However, they can also have adverse effects on the patient’s health. Several studies have shown that the information provided by the medical sales reps strongly influence the decision to add a drug to a prescription, often without the physician being fully aware of the side effects. In order to find out more, international researchers carried out an accurate study on the quality of the information given by medical sales reps when promoting drugs to physicians.

4 sites were selected: Vancouver, Montreal, Sacramento and Toulouse. The physicians were selected by a draw. Of the 704 physicians contacted, 36% agreed to participate. Then information was gathered about 1692 drugs promoted by medical sales reps between May 2009 and June 2010.

After each visit from the sales rep, the physicians were asked to fill in a questionnaire about how the drugs were promoted by the sales rep: they gave information (benefits and risks) about each promoted product, handed out free samples and gave invitations to events.

An overall lack of information

In this study, the researchers reported that the information given by the medical sales reps concentrated on the benefits of the drugs presented more often than their potential risks.

 And the same situation was reported for all sites in the study (Montreal, Sacramento, Toulouse and Vancouver). During more than half of the visits made to promote drugs (59%), the sales rep did not mention any adverse effects at all. This figure rose to 66% for Vancouver and Montreal.

Even more worrying: the results showed that “serious” side effects of drugs were only mentioned in 6% of the sales promotions.

France may be a model student, but…..

France differs from other countries by the fact that that the risks are mentioned more often by the sales reps: in 61% of cases to be exact.

But the overall figure taking into account all the countries involved in the study gave an average of only 41%.

However, this figure must be considered with caution, because the information given mainly concentrated on frequent and benign side effects (such as nausea, diarrhoea), whereas, in the other sites, 94% of presentations mentioned no “serious” side effect whatsoever.

On the other hand, the therapeutic benefits are highlighted in 80% of cases.

fig-benéfice-risque

 

Physicians are willing to prescribe promoted drugs

In this study and whatever the country, 2/3rds of physicians declared that the presentation would encourage them to prescribe a promoted product, or would “probably” or “very probably” incite them to prescribe this product more often.

surconsommation de médicaments,sécurité sociale

©Fotolia

What are the rules applicable to medical sales reps?

In France and in the USA, government authorities in charge of medication regulations are in charge of the rules and supervision of medical sales rep presentations at physicians’ surgeries. In France an additional approach was introduced in 2005. It is known as the Charter of Ethics for Pharmaceutical Sales Visits. This charter sets out the authorized and the prohibited practices and the information that must be given to the physician.

In Canada, the medical sales rep visits are regulated by Canada’s research-based pharmaceutical companies (Rx& D), who set out criteria concerning the information to be given to the physician.

The Health and Care of Pregnant Women and Babies in Europe in 2010

Posted on by Priscille Rivière

Second European Perinatal Health Report released by the Euro-Peristat project

The burden of mortality and morbidity in the perinatal period – pregnancy, childbirth, and the postpartum – remains a major concern in Europe. Over 5 million women deliver babies in European countries every year. A healthy pregnancy and infancy confers long-lasting benefits by preventing death and disability in childhood, and reducing risks of adult chronic diseases such as diabetes and hypertension.

The European Perinatal Health Report released by the Euro-Peristat project is the most comprehensive report on the health and care of pregnant women and babies in Europe and brings together data from 2010 from 26 European Union member states, plus Iceland, Norway and Switzerland. Euro-Peristat takes a new approach to health reporting. Rather than simply comparing countries on single indicators such as infant mortality, our report paints a fuller picture by presenting data about mortality, low birthweight and preterm birth alongside data about health care and maternal characteristics that can affect the outcome of pregnancy. It also illustrates differences in the ways that data are collected and explains how these can affect comparisons between countries.

The first Euro-Peristat report, with data for 2004, was published in 2008. It found wide differences between the countries of Europe in indicators of perinatal health and care. Documenting these differences is important because it shows that gains are possible in most countries, provides information about alternative ways of providing care, and raises important questions about the effectiveness of national healthcare policies and the role of evidence in maternity care. This second report provides the opportunity to see whether these gains have been achieved and whether inequalities between the countries of Europe have narrowed.

The 250-page European Perinatal Health Report is a major feat of collaboration between researchers and official statisticians in Europe. It also contains data from two other European projects: Surveillance of Cerebral Palsy in Europe (SCPE) and European Surveillance of Congenital Anomalies (EUROCAT).The Euro-Peristat project is cofinanced by the Health Programme of the European Union’s Directorate General for Health and Consumers which also provides funding for SCPE and EUROCAT.

Report highlights

HEALTH OUTCOMES

Fetal, neonatal, and infant mortality fell across-the-board in Europe between 2004 and 2010, but these declines were not equally distributed.

  • Fetal, neonatal and infant mortality rates declined by approximately 20%.
  • Declines were most pronounced in countries with higher mortality rates in 2004 (including Denmark, Italy, and the Netherlands for fetal mortality and Estonia, Latvia, and Lithuania for neonatal mortality).
  • Fetal, neonatal and infant mortality rates also fell in some countries with very low mortality in 2004 (including Slovenia, Finland, the Czech Republic and Austria), a decline showing that further decreases are possible.

Declines in mortality did not narrow the wide differences between European countries.

  • Fetal mortality rates at or after 28 weeks of gestation ranged from under 2.0 per 1000 live births and stillbirths in the Czech Republic and Iceland to 4.0 or more per 1000 in France, Latvia, the region of Brussels in Belgium, and Romania. The countries of the United Kingdom also had relatively high fetal mortality rates.
  • Neonatal mortality rates ranged from 1.2 per 1000 live births in Iceland and 1.5 per 1000 in Finland and Sweden to 4.5 per 1000 in Malta and 5.5 per 1000 in Romania.
  • Infant mortality rates ranged from 2.3 per 1000 live births in Iceland and Finland to 5.5 in Malta, 5.7 in Latvia, and 9.8 in Romania.

Preterm birth rates stayed the same or declined in many countries. Previous reports, including a new study issued by the Euro-Peristat group (see below) have found increases in overall preterm birth rates over the past 15 years. In contrast, our data for 2010 suggest that increases may have stopped in some countries. Understanding why these rates have stabilised or decreased in some countries can help shape health policies in countries where rates continue to rise.

European congenital anomaly registries (in the EUROCAT network) recorded a total prevalence of major congenital anomalies of 25.5 per 1000 births for 2006-2010. The prevalence among live births was 20.9 per 1000 births. Extrapolating to the EU-27, this represents approximately 112 000 affected live births. Although most fetuses affected by a congenital anomaly survive the first year of life, these anomalies are a major contributor to fetal and neonatal deaths. The total perinatal mortality rate associated with congenital anomaly was 0.81 per 1000 births. Rates of termination of pregnancy for fetal anomaly varied between regions and countries from 0 to 10.5 per 1000 births. The decade through 2010 saw shallow declines in the prevalence of non-chromosomal anomalies including neural tube defects and congenital heart defects and an increase in some congenital anomalies including Down syndrome and Gastroschisis.

Cerebral palsy affects one newborn in 500 per year. Population-based registries across Europe have shown a decrease in cerebral palsy rates in children born with very low birth weight or moderate gestational age.

Maternal deaths are rare in Europe, but under-reporting is widespread. The maternal mortality ratio (MMR) ranges from under 3 per 100 000 (in Estonia, Italy, Austria, and Poland) to over 10 per 100 000 live births (Latvia, Hungary, Slovenia, Slovakia, and Romania). Although considerable variation arises from the very small numbers of deaths involved, there is good evidence that maternal deaths derived from routine statistical systems are under-reported. This must be investigated particularly for countries where ratios are very low.

CHARACTERISTICS OF CHILDBEARING WOMEN    

Some risk factors for poor perinatal outcome increased, while others decreased. Levels of risk vary greatly between countries.

  • Multiple pregnancies: Multiple pregnancy rates differ widely throughout Europe, ranging from lows of 9 to 13 per 1000 women with live births or stillbirths in Romania, Latvia, Lithuania, and Poland to more than 20 per 1000 in Brussels, the Czech Republic, Denmark, Cyprus, Spain, and Malta. However, rates rose in 20 of the 23 countries that provided data on this indicator in both time periods. Babies from multiple births are 10 times more likely than singletons to be delivered preterm and as a result have higher risks of neonatal and infant death.
  • Maternal age: Since 2004, the average age of women giving birth in Europe has risen, but the proportions of mothers 35 years and older vary between countries from 10.9% in Romania to 34.7% in Italy. Births to mothers aged under 20 are uncommon (2% or lower in many countries), but in some countries, they account for over 5% of births (United Kingdom, Hungary, Latvia, Malta, Slovakian, and Romania.
  • Smoking during pregnancy: Our data show a decline over time in countries for which these data were available. In many countries, however, more than 10% of women continue to smoke during pregnancy. Countries with highest proportions of smokers were:  Spain (data from Catalonia – 14.4%), France (17.7%), and some UK countries, including Scotland (19%), Wales (16%), Northern Ireland (15%). Eleven countries had no data on this indicator.
  • Underweight, overweight and obesity: Data on maternal prepregnancy body mass index were collected for the first time in this report although 18 countries did not have these data. In many countries, more than 10% of pregnant women were obese, with highs in Wallonia in Belgium (13.6%), Germany (13.7%), and Scotland (20.6%).

HEALTH SERVICES

Caesarean section rates increased in most countries between 2004 and 2010. With the exception of Finland and Sweden, where rates declined, increases were widespread ranging from under 0.2% in Italy to over 7% in Lithuania, Slovakia, and Poland. In general, increases were most marked in the countries of central and eastern Europe and in Germany and Austria.

Practices related to caesarean section have not converged over time. Rates in 2010 ranged from 52.2% in Cyprus, 38.0% in Italy, 36.9% in Romania and 36.3% in Portugal to below 20% in the Netherlands, Slovenia, Finland, Sweden, Iceland, and Norway. Differences in population risk factors for caesarean section, such as maternal age and parity do not suffice to explain these wide differences. Among countries with high proportions of older mothers Italy and Portugal had high caesarean section rates while the Netherlands and Finland had lower rates.

Variations in obstetric practices raise questions about the role of scientific evidence in clinical decision making. In addition to caesarean, other aspects of clinical practice also varied widely. For example, episiotomy rates ranged from 5% to 70% of vaginal deliveries, yet current evidence does not support routine use of this procedure. Rates were around 70% in Cyprus, Poland, Portugal, and Romania and ranged from 43-58% in Wallonia and Flanders in Belgium and in Spain. The lowest rates – between 5 and 7% – were reported in Denmark, Sweden, and Iceland.

Up to 5 to 6% of births in some countries may occur after use of some form of assisted reproductive techniques (ART), although the use of the less invasive procedures is under-reported in most data systems or not reported at all. Births after in vitro fertilisation (IVF) accounted for 2 to 4% of all births. Many countries are implementing policies to prevent multiple pregnancies in assisted conception, and the decrease in twin rates observed in some countries – such as Denmark, the Netherlands and Norway – may be the result of these policies. In contrast, the substantial increases in twin birth rates observed in Italy, Malta, Luxembourg, Brussels in Belgium and the Czech Republic could result from more widespread use of ART without clear practice guidelines.

While the proportion of births in larger maternity units has increased in many countries, the size of maternity units still varies widely. Overall, few births occurred in maternity units with fewer than 500 births in 2010, but this proportion was higher in some countries (16.1% in Germany, 17.6% in Estonia, 18.3% in Switzerland, and 61.9% in Cyprus). At the other end of the spectrum, in Denmark, Ireland, Latvia, Slovenia, Sweden, England and Scotland, over one quarter of births take place in maternity units with 5000 or more deliveries per year.

THE FUTURE OF PERINATAL HEALTH REPORTING IN EUROPE

European countries face common challenges related to the health and care of mothers and babies as shown by the results of this and the previous Euro-Peristat report. By making its perinatal health indicators widely available to health planners, clinicians, researchers and users, Euro-Peristat seeks to promote evidence-based actions to improve maternal and child health. Yet to build a truly sustainable system, further actions are needed to:

Improve national capacity for perinatal health reporting by ensuring that each country can provide the full set of Euro-Peristat indicators using appropriate definitions as well as by improving ascertainment of very preterm births and maternal deaths. Wider linkage of data sources, building on methods already in use in Europe, could yield immediate gains for perinatal health monitoring in many countries.

Reinforce European collaborations to produce and use these data. The Euro-Peristat network has published 20 articles in peer-reviewed journals based on these data. Other researchers have also used the Euro-Peristat data for research on perinatal health in their own countries. We expect that these new data from 2010 – which allow exploration of time trends in maternal and infant health–to further highlight the value of having comparable data from the countries in Europe.

Notes to editors:

  • On May 27th, the Euro-Peristat project released the European Perinatal Health Report: The health and care of pregnant women and their babies in 2010. It can be downloaded free of charge as a PDF from http://www.europeristat.com.
  • Funding: Support comes from the European Union’s Health Programme
  • The Euro-Peristat project is coordinated by the Institut de la santé et de la recherche médicale (INSERM) in Paris. Data collection is coordinated by TNO, the Netherlands

Analysis of metabolic fingerprints of pregnant women living in proximity to cereal farming areas

Posted on by Priscille Rivière

An exploratory study published today by Sylvaine Cordier and her team (“Health, Environment and Work Research Institute”, a mixed Research Unit with input from Inserm, the Université de Rennes 1 and the Ecole des Hautes Etudes en Santé Publique) and researchers from Inra in Toulouse, suggests that environmental exposure to complex pesticide mixtures could led to metabolic disturbance in pregnant women. Observations indicate that concentrations of elements, such as amino acids or other organic acids, were modified in the urine of the pregnant women, suggesting an oxidative stress and a modification of the energy metabolism. The study was performed on 83 pregnant women from the PELAGIE cohort (Brittany), who were split into three groups, according to the areas of land dedicated to agricultural cereal activities in their town of residence. Details of the research are published in the PLOS ONE review.

Using pesticides can lead to the contamination of different environmental media (air, water, soil, food). As a consequence, exposure of the general public is possible, as shown by the presence of some pesticides in biological fluids and tissues. In addition to dietary exposure, exposure of the general public may result from the use of pesticides at home (use of household and gardening insecticides, etc.) and in proximity to the home. Pesticides used by professionals are dispersed into the atmosphere and could be a source of population exposure at varying distances from the area treated.

During pregnancy, the foetus is particularly vulnerable to environmental factors and low doses of toxic substances could be responsible for development disorders and trans-generational health effects.

Although the toxicity in high exposure conditions of several pesticides is well documented, questions remain about the effects of low doses of these molecules (environmental). Furthermore, as yet little is known about the impact of a combination of these exposure types. In addition to studies into the presence of pesticide residue in human biological fluids, one of the possible approaches to take account of these multiple exposures is to study the biological modifications in the exposed organism. The objective is to improve understanding of the mechanisms involved in exposure to pollution. The modifications can be identified by performing an overall analysis of metabolites in biological fluids (metabolic fingerprinting). Metabolites are small molecules involved in the functioning of the organism to sustain cell growth, balance and functions. Examples of metabolites are amino acids, small-sized organic acids (citric acid, hippuric acid), sugar, simple fatty acids, hormones, polyphenols, vitamins, alkaloids, minerals, etc.

This exploratory approach was implemented in 2004 using a sample of 83 pregnant women, taken from the PELAGIE (Endocrine disrupters: longitudinal study into pregnancy anomalies, infertility and childhood) mother-child cohort, which has been run by Inserm in Brittany since 2002. Three groups of women were composed in accordance with the proportion of cereal farming in their town of residence. The metabolites in the urine of these women, sampled during the first trimester of pregnancy, were characterized using a spectroscopic analysis technique (nuclear magnetic resonance) combined with a statistical method used to distinguish the three groups. The technique thus identified the metabolites for which the level of expression is modified between the three groups.

The first results of this study suggest modifications to the concentration of some metabolites in the urine of pregnant women living in towns with high levels of cereal farming; in particular, metabolites that may be involved in oxidative stress mechanisms and in the modification of the energy metabolism.

These elements led the researchers to suggest that environmental exposure to complex mixtures of pesticides, such as those used in 2004 on cereal crops, could lead to metabolic disturbances in pregnant women, for which the clinical significance, for the woman or her child, is yet to be assessed.

This is the first exploratory study conducted by Inserm Unit 1085 (IRSET) in Rennes, the Université de Rennes 1 and the Ecole des Hautes Etudes en Santé Publique (EHESP), in partnership with INRA in Toulouse (Toxalim). The study is part of a global research project that combines epidemiological research with toxicology studies to better understand metabolic pathways modified during multiple and complex exposure to pesticides (METABOLE project, www.irset.org). Ultimately, these elements could be used to better understand the effects of pesticides on health.

The “Young Researchers” congress to be held in 5 towns in France, on the theme of addiction

Posted on by Priscille Rivière

Over the whole school year, 20 middle school and high school pupils were seen each month in 5 neuroscience laboratories specializing in the study of addictions.

Goals: to change the attitude of these budding “apprentice researchers” to the hidden side of drugs (alcohol, tobacco, cannabis, etc.) and to addictions and to make for easier contact between youngsters and the world of research.
Starting soon on May 30th, the Young Researchers will present their research during five conference to be held in Poitiers (May 30), Amiens (June 4), Paris (June 5), Bordeaux (June 6) and Marseille (June 10).
The MAAD programme (Mechanisms of Addiction to Alcohol and Drugs) launched by Inserm with the support of the MILDT (the Interministerial mission for the fight against drugs and drug addiction) uses a “scientific education” type of approach that attempts to give these youngsters a better understanding of the products involved by introducing them to the scientific process.

One Wednesday per month, five research laboratories specialising in the pathology of addiction worked with teams consisting of a fourth-year junior school student and a middle-year high school student[1]. Working under the auspices of a senior researcher, the youngsters ran a research programme, carried out experiments and interpreted the results.

The 5 conferences held in the different research centres involved will provide information useful to all our Young Researchers. The audience will be made up of their classmates, parents, teachers, etc – and the public. These conferences are open to all and are free.

In Paris, the conference will take place on Wednesday June 5, 2015 at 18H30
in the Salle Polyvalente du SHU Sainte-Anne, 108 rue de la Santé, Paris
Danièle Jourdain Menninger, President of the MILDT, will be there for the occasion

The presentations given by the Young Researchers will be followed by a debate chaired by Laurence Lanfumey-Mongrédien, an Inserm researcher. The theme will be: “Drinking alcohol while young: the consequences in adult life”

Poitiers conference: Thursday May 30, 2013 at 18H30
Amiens conference: Tuesday June 4, 2013 at 18H00

Bordeaux conference: Thursday June 6, 2013 , at 18H00
Marseille conference: Monday June 10, 2013 , at 18H00

The consumption by young people of psychoactive products (alcohol, tobacco, cannabis, etc.) is causing constant concern for the health authorities, because it is now known that consumption at an early age while the brain is still in its developing stage, is a factor that favourises the development of dependence once adult age is reached. This campaign to arouse awareness of the toxicity of drugs is trying to bring an innovatory light to the other more conventional methods (radio spots, video clips, newspapers, mini-conferences inside schools and educational establishments, etc.).

[1]   The 5 laboratories who participated are: Amiens (Inserm ERI 24, Pr Mickaël Naassila), Bordeaux (Inserm U862 Magendie Neurosciences, Pr. Véronique Deroche), Marseille (UMR 7289 CNRS cognitive neurobiology laboratory, Dr Christelle Baunez), Paris (Inserm UMR 894, Dr. Laurence Lanfumey-Mongrédien) and Poitiers (Laboratory of experimental neurosciences and Inserm Clinic U1084, Pr. Mohamed Jaber).

Vesicular transport: a requirement for T immune response

Posted on by Priscille Rivière

T-lymphocyte (TL) activation requires recognition by the T-cell receptor (TCR) of the ligands present on the antigen-presenting cell (APC). The ligand–TCR link bound to the TL plasma membrane  introduces a signalling cascade that converts a signal received from the outside into a suitable response, for example cytokine secretion. Claire Hivroz, INSERM Research Director (INSERM Unit 932, Institut Curie, Paris) and her colleagues recently showed in an article published in Nature immunology how a specific protein known as VAMP7 is essential for transporting the signal produced by the ligand–TCR link. 

The setting up of this activation cascade has been the subject of numerous research papers and yet remains little known. In particular, the location of the cell in which the signalling occurs and the mechanisms governing the formation of the protein complexes needed for such activation remain the subject of controversy.

Claire Hivroz’s team showed in 2004 that a protein that played a key role in TCR signalling, the LAT molecule, acts as a framework on which the other signalling proteins are assembled. It is present on the plasma membrane and in each of the intra-cellular vesicles. In response to TCR stimulation, these vesicles are attracted to the area in which the stimulation takes place, namely, the contact area between the TL and the APC, known as the immunological synapse (IS).

ImageJ=1.46i

Crédit photo : © Inserm-Institut Curie/C. Hivroz

Evanescent wave microscopy image showing recruitment into the immunological synapse of LAT-containing vesicles (magenta), VAMP7 (green) or the two proteins (white) in a T-lymphocyte interacting with a glass slide covered in activating antibodies (INSERM–Institut Curie/C. Hivroz)

 

Researchers wanted to discover the role played by this intracellular LAT ‘pool’ and the mechanisms that lie behind its recruitment by the IS. The study being published this month in Nature Immunology was performed in collaboration with Thierry Galli, a specialist in the proteins involved in the transport of vesicles to the neurological synapse, known as SNARE proteins, involved in membrane fusion reactions during vesicular transport.

By using genetically modified mice, RNA interference mechanisms and high-resolution microscopy, Claire Hirvoz’s team showed that VAMP7, a SNARE protein, is necessary for transporting LAT-containing vesicles to the IS. This transport controls LAT activation and the formation of the protein complex that sets up the signalling cascade. Consequently, T-lymphocytes deprived of VAMP7 will not respond normally to stimulation of their TCRs.

In conclusion, this new data will contribute to understanding the way in which information is propagated over time and space after TCR stimulation and shows for the first time how the transport of vesicles is involved in setting up a response to T-lymphocytes.

These results also show that molecules present in the neuronal synapses and involved in their functions are also involved in the functions of the immunological synapse.

Discovery of a molecule derived from cholesterol that has anti-cancer properties

Posted on by Priscille Rivière

Although excessive quantities of cholesterol in the body are known to have adverse effects on health, researchers might polish up its reputation via one of its derivatives. The research team from Inserm and the CNRS led by Marc Poirot and Sandrine Silvente-Poirot at the “Centre de recherche en cancérologie de Toulouse” (Inserm / CNRS / Université Toulouse III – Paul Sabatier), has not only discovered a new molecule derived from cholesterol (known as dendrogenine A), but has also provided proof in mice that this molecule has anti-cancer properties.

This work has been published in the journal Nature Communications.

Cholesterol is involved in different chronic pathologies, such as cardiovascular diseases and cancer. Current knowledge led us to suppose that cholesterol had a negative effect on cancers, mainly for two reasons. Firstly, cholesterol is a precursor of androgens and estrogens, both of which are involved in the development of cancers known as “hormone-dependent” cancers. Secondly, the synthesis process of cholesterol (that contains over 20 different stages) activates tumour-related genes.

Blocking the upstream biosynthesis pathway using inhibitors such as statins should have provided protection against cancer or some measure of anti-cancer efficiency, but this was not confirmed by clinical studies involving very large patient cohort studies; This suggests that its metabolism is much more complicated[1].

So the team of researchers led by Marc Poirot and Sandrine Silvente-Poirot concentrated particularly on the metabolism of cholesterol. Using screening and chemical synthesis techniques, the researchers were able to show that the product of the chemical reaction between a cholesterol derivative and a histamine generates a new class of sterols known as Dendrogenine A (DDA). This molecule, obtained in laboratory conditions, shows remarkable properties for inducing differentiation and death of cancer cells.

These observations led the team to search for this molecule in the tissues of mammals. And they discovered that DDA is present in healthy tissue and cells in humans, whereas it is not detectable in tumour cells. In women, its level is 5 times lower in breast tumour tissue than in normal tissue.

“Our results suggest that DDA protects the cells from carcinogenic processes” points out Marc Poirot.

In order to test this hypothesis, the researchers then attempted to repair the DDA deficiency in tumours implanted in animals. And in these animals, the administration of DDA controlled the proliferation of the tumour and extended the life expectancy.

For the researchers, this is a major discovery, because it provides the proof of the existence of a new metabolic pathway in humans, at the interface between the cholesterol metabolism and the histamine metabolism, and also because, thanks to its anti-cancer properties, DDA could be used to treat different cancers.

 Dendrogine_ENG

© Sandrine Silvente-Poirot / Marc Poirot

[1] A group of processes than involve both synthesis and breakdown of cholesterol into products that can be used by the body.

 

Chikungunya: discovery of a human-specific factor involved in the virus replication

Posted on by Priscille Rivière

Scientists from the Institut Pasteur, Inserm and CNRS, have identified a human-specific factor involved in the replication of Chikungunya virus which accounts for the species specificity of this virus. Chikungunya virus is an emerging virus that in 2005 caused, for the first time, an outbreak in La Réunion island, a French overseas district where more than 30% of the population was infected, and has recently emerged in temperate regions of Europe. The identification of this new host factor enriches our understanding of the molecular bases of Chikungunya virus infection, which were characterized so far. This work also paves the way for the development of a more relevant humanized animal model to better understand the pathophysiology of infection.
This research has been published online on April 26, at the European Molecular Biology Organization reports (EMBO reports).

Chikungunya virus was first identified in Tanzania in the 1950s and emerged in the islands of the Indian Ocean in 2005 where it caused a large outbreak, most notably in La Réunion island. In 2007, this virus was imported to Europe, causing an outbreak in Italy. In late summer 2010, the two first autochthonous cases were reported in the French Riviera.

Virus Chikungunya à la surface d'une cellule

Copyright Institut Pasteur / Thérèse Couderc

The molecular mechanisms of Chikungunya virus infection in human cells have been poorly characterized. Scientists at the Institut Pasteur, Inserm and CNRS, under the leadership of Marc Lecuit, head of the Biology of Infection Unit at the Institut Pasteur in Paris, have made a significant advance: they have identified a human-specific intracellular molecular factor called NDP52 that is involved in the replication of Chikungunya virus. The scientists have demonstrated that in human cells, NDP52 is able to bind to a protein of Chikungunya virus, nsP2, and that this interaction promotes the replication of the virus inside its target cells, thereby contributing to the development of human Chikungunya virus infection. In contrast, mouse NDP52 does not interact with nsP2, and NDP52 therefore does not promote infection in murine cells.

In 2008, the team headed by Marc Lecuit had developed the first animal model to experimentally reproduce the human disease caused by Chikungunya virus. This animal model has since allowed a better understanding of the physiopathology of infection, and has enabled the identification of Chikungunya virus target cells and tissues to test the efficacy of preventive and curative approaches. The discovery of the role of the human factor NDP52 in Chikungunya virus infection opens new avenues for the development of a humanized animal model, which would be instrumental for deeper understanding of the pathophysiology of Chikungunya virus infection.

Handicaps rares, contextes, enjeux et perspectives : une expertise collective de l’Inserm

Posted on by Priscille Rivière
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