Abrupt changes of hydrothermal activity in a lava dome detected by combined seismic and muon monitoring.

The recent 2014 eruption of the Ontake volcano in Japan recalled that hydrothermal fields of moderately active volcanoes have an unpredictable and hazardous behavior that may endanger human beings. Steam blasts can expel devastating ejecta and create craters of several tens of meters. The management of such hydrothermal events in populated areas is problematic because of their very short time of occurrence. At present no precursory signal is clearly identified as a potential warning of imminent danger. Here we show how the combination of seismic noise monitoring and muon density tomography allows to detect, with an unprecedented space and time resolution, the increase of activity (at timescales of few hours to few days) of a hydrothermal spot located 50 to 100 m below the summit of an active volcano, the La Soufrière of Guadeloupe, in the Lesser Antilles. We show how the combination of those two methods improves the risk evaluation of short-term hazards and the localization of the involved volumes in the volcano. We anticipate that the deployment of networks of various sensors including temperature probes, seismic antennas and cosmic muon telescopes around such volcanoes could valuably contribute to early warning decisions.

Reflection on the measurement and use of the topography of the indentation imprint.

The goal of this paper is to study the main uses of the residual imprint of the indentation test. It also discusses the different technologies and methods employed in this context. The difficulties encountered when trying to exploit the full potentials of the imprint are thoroughly examined. A survey of the literature on the quantification of the pile-up clearly shows that there is a lack of consensus on the measurement of the residual imprint as well as on treatment methods. Therefore, in order to widen the application fields of the indentation residual imprint, relevant and standardized indicators should be established.

Genomics and the prospects of existing and emerging therapeutics for cardiovascular diseases.

The growing knowledge about genetic influence on cardiovascular diseases (CVD) combined with the recently generated amounts of genomic data hold promise to the identification of new markers for atherosclerotic CVD. Cardiovascular pharmacogenomics and pharmacogenetics have now the potential for leading to identification of genetic contributors and therefore to the development of predictive genetic tests that could optimize drugs efficacy and minimize toxicity. Clinical studies have shown that genetic variations within cytochromes P450 (CYPs), 3-Hydroxyl-3-Methylglutaryl Coenzyme A Reductase (HMGCR) and apolipoprotein E (APOE) genes influence individual's response to lipid lowering statins. Furthermore, development of antagonists or inhibitors of molecules such as peroxisome proliferator-activated receptors (PPARs), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), angiotensin-converting enzyme (ACE), angiotensin receptors and tumor necrosis factor (TNF)-alpha could be another alternative to prevent atherosclerosis. In addition, novel molecules under the name of biologics including family of peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), urocortin, apelin and antimicrobial peptides (AMPs) could be considered as new targets for the prevention and treatment of CVD. In this article, we will focus mainly on recent genomic advances in the development of new markers and therapeutic agents for CVD. We present an array of molecules that could have pharmacological benefit for the treatment of heart disease. We also discuss in details new strategies including biologics, which are actually the focus of companies for clinical development of therapeutic drugs. All these efforts provide optimism and attractive promise to cure CVD.

Five-year alterations in BMI are associated with clustering of changes in cardiovascular risk factors in a gender-dependant way: the Stanislas study.

OBJECTIVE: The purpose of the present longitudinal study was to describe the associations between the 5-year changes in body mass index (BMI) and alterations in the clusters of metabolic syndrome (MS)-related factors. METHODS: The study population comprised 1099 middle-aged adults drawn from the Stanislas study. Individuals were stratified into four groups according to the 5-year changes in BMI (weight loss (<0 kg/m(2)), and weight gain (0-1, 1-2 and >2 kg/m(2))). Changes in various MS-related variables and clusters were compared between groups: anthropometric indices, blood pressure, lipid and inflammatory markers, liver enzymes, uric acid and the five summary factors extracted by using factor analysis ('risk lipids', 'liver enzymes', 'inflammation', 'protective lipids' and 'blood pressure'). RESULTS: There was a strong linear trend between increasing BMI and worsening of risk lipids and blood pressure factors for both men and women (P

P-selectin polymorphisms' influences on P-selectin serum concentrations and on their familial correlation: the STANISLAS family study.

BACKGROUND: P-selectin is an adhesion molecule known to be involved in the pathogenesis of several diseases through its major role in the initial phase of leukocytes recruitment during inflammation. However, genetic characterization of soluble P-selectin remains unclear. OBJECTIVES: In the STANISLAS cohort, we study the familial correlations of P-selectin levels and investigate the association of six P-selectin polymorphisms (C-2123G, A-1969G, S290N, N562D, V599L and T715P) and cardiovascular risk factors with P-selectin concentrations. PATIENTS/METHODS: Full phenotypic and genotypic information was available for 136 healthy families composed of both natural parents and at least one child (boys, n = 125; and girls, n = 139) aged more than 4 years. RESULTS: While no correlation was observed between spouses, family correlations of P-selectin concentrations were highly significant for sibling (0.50 +/- 0.12, P < 10(-3)) and child-parent pairs (0.42 +/- 0.04, P < 10(-3)). P-selectin haplotypes explained about 25% of the variability of P-selectin concentrations, this effect being mainly due to the additive effects of two polymorphisms, V599L and T715P. After adjusting for the effect of the P-selectin polymorphisms, the sibling and child-parent correlations decreased to (0.39 +/- 0.08, P < 10(-4)) and (0.32 +/- 0.06, P < 10(-4)), respectively. CONCLUSIONS: In the present study, we showed that two P-selectin polymorphisms, V599L and T715P, explained about 25% of the variability of P-selectin concentrations and accounted for about 40% of their family resemblance. These results would suggest a genetic influence on P-selectin concentrations beyond the contribution of the P-selectin gene.

[Pharmacogenomics and pharmacoproteomics: a strategy for cardio-vascular drugs]. / Pharmacogénomique et pharmacoprotéomique.

The development of personalized medicine will require improved knowledge of biological variability, particularly concerning the important impact of each individual's genetic makeup. A five-step strategy can be followed when trying to identify genes and gene products involved in differential responses to cardiovascular drugs: 1) Pharmacokinetic-related genes and phenotypes; (2) Pharmacodynamic targets, genes and products; (3) Cardiovascular diseases and risks depending on specific or large metabolic cycles; (4) Physiological variations of previously identified genes and proteins; (5) Environmental influences on them. After summarizing the most well known genes involved in drug metabolism, we used statins as an example. In addition to their economic impact, statins are generally considered to be of significant importance in terms of public health. Individuals respond differently to these drugs depending on multiple polymorphisms. Applying a pharmacoproteomic strategy, it is important to use available information on peptides, proteins and metabolites, generally gene products, in each of the five steps. A profiling approach dealing with genomics as well as proteomics is useful. In conclusion, the ever growing volume of available data will require an organized interpretation of variations in DNA and mRNA as well as proteins, both on the individual and population level.

Pharmacogenomics and drug response in cardiovascular disorders.

There are a total of 17 families of drugs that are used for treating the heterogeneous group of cardiovascular diseases. We propose a comprehensive pharmacogenomic approach in the field of cardiovascular therapy that considers the five following sources of variability: the genetics of pharmacokinetics, the genetics of pharmacodynamics (drug targets), genetics linked to a defined pathology and its corresponding drug therapies, the genetics of physiologic regulation, and environmental-genetic interactions. Examples of the genetics of pharmacokinetics are presented for phase I (cytochromes P450) and phase II (conjugating enzymes) drug-metabolizing enzymes and for phase III drug transporters. The example used to explain the genetics of pharmacodynamics is glycoprotein IIIa and the response to antiplatelet effects of aspirin. Genetics linked to a defined pathology and its corresponding drug therapies is exemplified by ADRB1, ACE, CETP and APOE and drug response in metabolic syndrome. The examples of cytochrome P450s, APOE and ADRB2 in relation to ethnicity, age and gender are presented to describe genetics of physiologic regulation. Finally, environmental-genetic interactions are exemplified by CYP7A1 and the effects of diet on plasma lipid levels, and by APOE and the effects of smoking in cardiovascular disease. We illustrate this five-tiered approach using examples of cardiovascular drugs in relation to genetic polymorphism.

[Contribution of cryotherapy to phlebology]. / Contribution de la cryothérapie en phlébologie.

Taking into account the results obtained by cryotherapy in proctology, the author has tried to apply this method in conjunction with microsclerosis in the treatment of telangiectasia. The results seem very encouraging on the whole, and could be considered an interesting contribution to the treatment of this obstinate and unattractive condition.

[Zollinger-Ellison syndrome treated medically by an inhibitor of H2 histamine receptors]. / Syndrome de Zollinger-Ellison traité médicalement par un inhibiteur des récepteurs H2 à l'histamine.

Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.