Hôpital-Camfrout, France
Hôpital-Camfrout, France

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Belguith-Hadriche O.,Laboratoire Of Biochimie | Bouaziz M.,University of Sfax | Jamoussi K.,Laboratoire Of Biochimie | Simmonds M.S.J.,Royal Botanic Gardens | And 2 more authors.
Food Chemistry | Year: 2013

The hypocholesterolemic and antioxidant activities of various extracts (water, methanol, ethyl acetate, hexane, dichloro-methane) of fenugreek seeds were investigated in cholesterol-fed rats. Only the ethyl acetate extract reduced total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) compared with those of rats fed a cholesterol-rich diet (HCD). Furthermore, the content of thiobarbituric acid-reactive substances (TBARS), and catalase and superoxide dismutase (SOD) in liver, heart and kidney decreased significantly after oral administration of the ethyl acetate extract, compared with those of HCD-fed rats. The phenolic and flavonoïd contents were highest in the methanol and the ethyl acetate extracts. These results showed that the ethyl acetate extract of the fenugreek seeds had a significant hypocholesterolemic effect and antioxidant activity in cholesterol-fed rats, whether this is partly due to the presence of flavonoïds in the extract needs further study. © 2012 Elsevier Ltd. All rights reserved.


Horcajada P.,Institut Universitaire de France | Chalati T.,University Paris - Sud | Serre C.,Institut Universitaire de France | Gillet B.,University Paris - Sud | And 15 more authors.
Nature Materials | Year: 2010

In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5 wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal-organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments. © 2010 Macmillan Publishers Limited. All rights reserved.


Daudon M.,APHP | Bouzidi H.,Laboratoire Of Biochimie | Bazin D.,University Paris - Sud
Urological Research | Year: 2010

Calcium phosphate (CaP) stones account for about 15% of all urinary stones, with a marked female pre ponderance, and reflect a wide diversity of etiology. Varia tion of the relative prevalence of CaP urolithiasis over time is disputed, and relevance of CaP stone analysis for etio- logic diagnosis is underestimated or even negated. Based on the analysis of more than 50,000 stones over the past three decades, we evaluated the changes in the relative pro portion of CaP stones between 1980-1989 (period 1) and 2000-2009 (period 2). In addition, using morphologic examination combined with Fourier-transform infrared analysis, we assessed the associations between CaP stone analysis and etiopathogenic factors. Between periods 1 and 2, the overall proportion of struvite-free stones remained essentially unchanged (11.6 vs. 11.1%), with a decreasing proportion of carbapatite stones (10.6 vs. 8.4%, p < 0.001) and a rising proportion of brushite stones (0.8 vs. 2.2%, p < 0.001). Hypercalciuria was associated with 87% of brushite, and 60% of carbapatite stones. Urinary tract infec tion was associated with presence of minor amounts of stru- vite and/or with a carbonation rate of carbapatite > 15%. In CaP stones associated with primary hyperparathyroidism, the main component was carbapatite in 66.9% and brushite in 29.1% of cases. Distal renal tubular acidosis was always associated with carbapatite stones exhibiting a peculiar, vir tually pathognomonic, morphology. In conclusion, compre hensive analysis of stones involving morphologic examination is of clinical relevance for improved etiologic evaluation of patients with CaP urolithiasis. © Springer-Verlag 2010.


Sinha B.,University Pierre and Marie Curie | Koster D.,University Pierre and Marie Curie | Ruez R.,French National Center for Scientific Research | Gonnord P.,French National Center for Scientific Research | And 16 more authors.
Cell | Year: 2011

The functions of caveolae, the characteristic plasma membrane invaginations, remain debated. Their abundance in cells experiencing mechanical stress led us to investigate their role in membrane-mediated mechanical response. Acute mechanical stress induced by osmotic swelling or by uniaxial stretching results in a rapid disappearance of caveolae, in a reduced caveolin/Cavin1 interaction, and in an increase of free caveolins at the plasma membrane. Tether-pulling force measurements in cells and in plasma membrane spheres demonstrate that caveola flattening and disassembly is the primary actin- and ATP-independent cell response that buffers membrane tension surges during mechanical stress. Conversely, stress release leads to complete caveola reassembly in an actin- and ATP-dependent process. The absence of a functional caveola reservoir in myotubes from muscular dystrophic patients enhanced membrane fragility under mechanical stress. Our findings support a new role for caveolae as a physiological membrane reservoir that quickly accommodates sudden and acute mechanical stresses. PaperFlick: © 2011 Elsevier Inc.


Bricker D.K.,University of Utah | Taylor E.B.,University of Utah | Schell J.C.,University of Utah | Orsak T.,University of Utah | And 12 more authors.
Science | Year: 2012

Pyruvate constitutes a critical branch point in cellular carbon metabolism. We have identified two proteins, Mpc1 and Mpc2, as essential for mitochondrial pyruvate transport in yeast, Drosophila, and humans. Mpc1 and Mpc2 associate to form an ~150-kilodalton complex in the inner mitochondrial membrane. Yeast and Drosophila mutants lacking MPC1 display impaired pyruvate metabolism, with an accumulation of upstream metabolites and a depletion of tricarboxylic acid cycle intermediates. Loss of yeast Mpc1 results in defective mitochondrial pyruvate uptake, and silencing of MPC1 or MPC2 in mammalian cells impairs pyruvate oxidation. A point mutation in MPC1 provides resistance to a known inhibitor of the mitochondrial pyruvate carrier. Human genetic studies of three families with children suffering from lactic acidosis and hyperpyruvatemia revealed a causal locus that mapped to MPC1, changing single amino acids that are conserved throughout eukaryotes. These data demonstrate that Mpc1 and Mpc2 form an essential part of the mitochondrial pyruvate carrier.


Wolf A.,Laboratoire Of Biochimie
Médecine tropicale : revue du Corps de santé colonial | Year: 2011

FAV-Afrique is a polyvalent snake antivenom, elaborated by immunisation of horses with venom from 10 different snake species among the most dangerous in Africa and belonging to Elapidae and Viperidea families. Only F(ab')2 fragments are kept and purified. This serum is able to decrease the quantity of circulating venom and therefore its toxicity. Its use is indicated as soon as the first signs of poisoning are observed (local oedema). Twenty millimetres are administrated via intra-venous route whatever the weight of the patient. Re-administration may be performed if improvement is not sufficient. Treatment should be initiated as soon as possible but can be realized as long as the symptoms are present. Side effects (allergy) should be considered but balanced with the seriousness of poisoning. There is no absolute contraindication or drug interaction reported with FAV-Africa. It is authorized and distributed in several African countries and has a temporary regulatory approval in France. The major limits to its use are high cost and storage conditions (maximum 36 months between +2 degrees C and +8 degrees C). In the future, the new serum Antivipmyn Africa, available as a freeze-dried product, which can be preserved at room temperature, should improve storage conditions and availability of treatment, especially in rural Africa.


Suffee N.,University of Paris 13 | Richard B.,University of Paris 13 | Oudar O.,University of Paris 13 | Charnaux N.,University of Paris 13 | And 3 more authors.
Biochemical Society Transactions | Year: 2011

Atherosclerosis is an inflammatory disease that is one of the leading causes of death in developed countries. This disease is defined by the formation of an atherosclerotic plaque, which is responsible for artery obstruction and affects the heart by causing myocardial infarction. The vascular wall is composed of three cell types and includes a monolayer of endothelial cells and is irrigated by a vasa vasorum. The formation of the vascular network from the vasa vasorum is a process involved in the destabilization of this plaque. Cellular and molecular approaches are studied by in vitro assay of activated endothelial cells and in in vivo models of neovascularization. Chemokines are a large family of small secreted proteins that have been shown to play a critical role in the regulation of angiogenesis during several pathophysiological processes such as ischaemia. Chemokines may exert their regulatory activity on angiogenesis directly by activating the vasa vasorum, or as a consequence of leucocyte infiltration through the endothelium, and/or by the induction of growth factor expression such as that of VEGF (vascular endothelial growth factor). The present review focuses on the angiogenic activity of the chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted)/CCL5 (CC chemokine ligand 5). RANTES/CCL5 is released by many cell types such as platelets or smooth muscle cells. This chemokine interacts with GPCRs (G-protein-coupled receptors) and GAG (glycosaminoglycan) chains bound to HSPGs (heparan sulfate proteoglycans). Many studies have demonstrated, using RANTES/CCL5 mutated on their GAG or GPCR-binding sites, the involvement of these chemokines in angiogenic process. In the present review, we discuss two controversial roles of RANTES/CCL5 in the angiogenic process. ©The Authors Journal compilation ©2011 Biochemical Society.


Paterlini-Brechot P.,University of Paris Descartes | Paterlini-Brechot P.,French Institute of Health and Medical Research | Paterlini-Brechot P.,Laboratoire Of Biochimie
Cancer Microenvironment | Year: 2014

This article is a critical note on the subject of Circulating Tumor Cells (CTC). It takes into account the tumor identity of Circulating Tumor Cells as cancer seeds in transit from primary to secondary soils, rather than as a “biomarker”, and considers the help this field could bring to cancer patients. It is not meant to duplicate information already available in a large number of reviews, but to stimulate considerations, further studies and development helping the clinical use of tumor cells isolated from blood as a modern personalized, non-invasive, predictive test to improve cancer patients’ life. The analysis of CTC challenges, methodological bias and critical issues points out to the need of referring to tumor cells extracted from blood without any bias and identified by cytopathological diagnosis as Circulating Cancer Cells (CCC). Finally, this article highlights recent developments and identifies burning questions which should be addressed to improve our understanding of the domain of CCC and their potential to change the clinical practice. © 2014, The Author(s).


Dhondt J.-L.,Laboratoire Of Biochimie
Journal of Inherited Metabolic Disease | Year: 2010

In addition to being hyperphenylalaninemic, patients lacking tetrahydrobiopterin (BH4) are deficient in the neurotransmitters whose synthesis depends on the normal activity of tetrahydrobiopterin-dependent tyrosine and tryptophan hydroxylases. Consequently, these patients have to be rapidly recognized among hyperphenylalaninemic babies, since they need specific and early substitutive therapy. Since 1980, BH4 metabolism has been investigated in 2,186 hyperphenylalaninemic babies, using HPLC measurement of pteridines in urine to recognize tetrahydrobiopterin synthesis deficiency (GTP cyclohydrolase and PTPS deficiency) and direct DHPR assay in dried blood samples to recognize DHPR deficiency. A total of 73 tetrahydrobiopterin deficient patients have been detected. Considering the group of neonates born in France (1,342), out of the 32 BH4 deficient patients which have been detected, only 8 were from caucasian families. The lessons from that experience are: (1) tests on blood and urine collected on filter paper cards commend itself by their convenience and simplicity, and samples can be collected on the first visit of the screened infants to the out-patient clinic; and (2) the preconceaved idea that newborns with moderate elevation of blood phenylalanine are false positives of the screening or mild forms of hyperphenylalaninemia explains that a significant number of cases were investigated after 1 month of age; however, in half of BH4- deficient babies, blood phenylalanine was below 10 mg/dl (0.6 mmol/l). © 2010 SSIEM and Springer.


Abbassi F.,Laboratoire Of Biochimie | Hani K.,Laboratoire Of Biochimie
Natural Product Research | Year: 2012

Rhus tripartitum (African sumac) is a plant commonly used in Tunisian traditional medicine to treat diarrhoea and dysentery. In this study, we have demonstrated that R. tripartitum extracts exhibited a significant broad spectrum activity against one or more of the test microorganisms with a zone size ranging from 8 to 28mm in diameter. These diameters are much higher than those obtained with standard antibiotics. The chloroformic extracts were found to be effective against bacterial and fungal strains tested, with MIC values ranging between 0.07 and 0.62mg mL-1 against Staphylococcus aureus and Candida albicans. However, ethyl-acetate/methanol fractions showed a selective activity only against bacterial microorganisms with low MIC values between 0.07 and 0.15m gmL-1. The overall results suggested that the traditional use of R. tripartitum for the treatment of diarrhoea tract infections was attributed to the presence of antibacterial agents. © 2012 Taylor & Francis Group, LLC.

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