Le rôle de l'hormone anti-müillerienne dans la régulation du fonctionnement de l'ovaire. Revue de la littérature

Anti-mullerian hormone, also called AMH, belongs to the large family of transforming growth factor P. Its role in the sexual differentiation of male fetus is now well known. Recently, AMH has been demonstrated to play an important role in the ovarian function. In fact, AMH seems to regulate the kinetics of follicular development, inhibiting the follicular recruitment and the follicular growth. Thus, this intra-gonadic cybernin could be a decisive determinant of the rapidity of follicular pool exhaustion. Today, some experimental data from the literature suggest that AMH could be a reliable marker of ovarian reserve. This review summarizes the present knowledge about AMH and its role in physiology but also in ovarian pathology.

Heparin-binding hemagglutinin, from an extrapulmonary dissemination factor to a powerful diagnostic and protective antigen against tuberculosis.

Interactions of Mycobacterium tuberculosis with macrophages have long been recognized to be crucial to the pathogenesis of tuberculosis. The role of non-phagocytic cells is less well known. We have discovered a M. tuberculosis surface protein that interacts specifically with non-phagocytic cells, expresses hemagglutination activity and binds to sulfated glycoconjugates. It is therefore called heparin-binding hemagglutinin (HBHA). HBHA-deficient M. tuberculosis mutant strains are significantly impaired in their ability to disseminate from the lungs to other tissues, suggesting that the interaction with non-phagocytic cells, such as pulmonary epithelial cells, may play an important role in the extrapulmonary dissemination of the tubercle bacillus, one of the key steps that may lead to latency. Latently infected human individuals mount a strong T cell response to HBHA, whereas patients with active disease do not, suggesting that HBHA is a good marker for the immunodiagnosis of latent tuberculosis, and that HBHA-specific Th1 responses may contribute to protective immunity against active tuberculosis. Strong HBHA-mediated immuno-protection was shown in mouse challenge models. HBHA is a methylated protein and its antigenicity in latently infected subjects, as well as its protective immunogenicity strongly depends on the methylation pattern of HBHA. In both mice and man, the HBHA-specific IFN-gamma was produced by both the CD4(+) and the CD8(+) T cells. Furthermore, the HBHA-specific CD8(+) T cells expressed bactericidal and cytotoxic activities to mycobacteria-infected macrophages. This latter activity is most likely perforin mediated. Together, these observations strongly support the potential of methylated HBHA as an important component in future, acellular vaccines against tuberculosis.

5-Fluorouracil: mechanisms of action and clinical strategies

5-fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.

Second-to-Fourth Digit Ratio and Impulsivity: A Comparison between Offenders and Nonoffenders

Personality characteristics, particularly impulsive tendencies, have long been conceived as the primary culprit in delinquent behavior. One crucial question to emerge from this line of work is whether impulsivity has a biological basis. To test this possibility, 44 male offenders and 46 nonoffenders completed the Eysenck Impulsivity Questionnaire, and had their 2D:4D ratio measured. Offenders exhibited smaller right hand digit ratio measurements compared to non-offenders, but higher impulsivity scores. Both impulsivity and 2D:4D ratio measurements significantly predicted criminality (offenders vs. nonoffenders). Controlling for education level, the 2D:4D ratio measurements had remained a significant predictor of criminality, while impulsivity scores no longer predicted criminality significantly. Our data, thus, indicates that impulsivity but not 2D:4D ratio measurements relate to educational attainment. As offenders varied in their number of previous convictions and the nature of their individual crimes, we also tested for differences in 2D:4D ratio and impulsivity among offenders. Number of previous convictions did not correlate significantly with the 2D:4D ratio measurements or impulsivity scores. Our study established a link between a biological marker and impulsivity among offenders (and lack thereof among non-offenders), which emphasise the importance of studying the relationship between biological markers, impulsivity and criminal behavior.

Study of aflatoxin exposure in a Brazilian population using an aflatoxin - albumin biomarker

The evaluation of exposure to aflatoxins (AF) by measurement of the level of contamination in food is hampered due to the heterogeneous distribution of AF in food. Therefore, an alternative is to estimate the exposure using specific biological markers (biomarkers) based on an understanding of the metabolism of the compound. For AF, these include aflatoxin-N-7-guanine in the urine, or AFB(1)-albumin (AF-alb) in the blood. This study assessed the level of exposure to AF in Brazilian individuals using a biomarker approach, i.e. the AF-alb adducts. Blood samples were collected from urban residents (n=50; aged 18-52) in June 1999, at the Blood Center of Antonio Carlos de Camargo Hospital, Sao Paulo, Brazil. AF-alb adduct levels were determined, by ELISA following serum albumin extraction and digestion. AF-alb adducts were detected in 31/50 (62%) samples [range 0-57.3 pg AFB(1)-lys adducts/mg of blood albumin (pg/mg)]. The mean level of positives was 14.9 pg/mg and males had the two highest levels measured (57.1 and 57.3 pg/mg). There was no correlation with age or profession. This is the first study of Brazilian, or indeed South American, individuals that has determined exposure to AF at the individual level using a biomarker approach. These levels are similar to those observed in the Philippines. These data warrant further investigation of both the sources and consequences of exposure to this potent toxin in Brazil.

Determining mycotoxins and mycotoxigenic fungi in food and feed:Developing biomarkers of human exposure to mycotoxins

Exposure assessment is a critical part of epidemiological studies into the effect of mycotoxins on human health. Whilst exposure assessment can be made by estimating the quantity of ingested toxins from food analysis and questionnaire data, the use of biological markers (biomarkers) of exposure can provide a more accurate measure of individual level of exposure in reflecting the internal dose. Biomarkers of exposure can include the excreted toxin or its metabolites, as well as the products of interaction between the toxin and macromolecules such as protein and DNA. Samples in which biomarkers may be analysed include urine, blood, other body fluids and tissues, with urine and blood being the most accessible for human studies. Here we describe the development of biomarkers of exposure for the assessment of three important mycotoxins; aflatoxin, fumonisin and deoxynivalenol. A number of different biomarkers and methods have been developed that can be applied to human population studies, and these approaches are reviewed in the context of their application to molecular epidemiology research.

A novel three-dimensional culture system for isolation and clonal propagation of neural stem cells using a thermo-reversible gelation polymer

In the present study, we examined the possible utility of a three-dimensional culture system using a thermo-reversible gelation polymer to isolate and expand neural stem cells (NSCs). The polymer is a synthetic biologically inert polymer and gelates at temperatures higher than the gel-sol transition point ( approximately 20 degrees C). When fetal mouse brain cells were inoculated into the gel, spherical colonies were formed ( approximately 1% in primary culture and approximately 9% in passage cultures). The spheroid-forming cells were positive for expression of the NSC markers nestin and Musashi. Under conditions facilitating spontaneous neural differentiation, the spheroid-forming cells expressed genes characteristic to astrocytes, oligodendrocytes, and neurons. The cells could be successively propagated at least to 80 poly-D-lysines over a period of 20 weeks in the gel culture with a growth rate higher than that observed in suspension culture. The spheroids formed by fetal mouse brain cells in the gel were shown to be of clonal origin. These results indicate that the spheroid culture system is a convenient and powerful tool for isolation and clonal expansion of NSCs in vitro.

Molecular mapping the presence of druggable targets in preinvasive and precursor breast lesions:a comprehensive review of biomarkers related to therapeutic interventions

The analysis of clinical breast samples using biomarkers is integral to current breast cancer management. Currently, a limited number of targeted therapies are standard of care in breast cancer treatment. However, these targeted therapies are only suitable for a subset of patients and resistance may occur. Strategies to prevent the occurrence of invasive lesions are required to reduce the morbidity and mortality associated with the development of cancer. In theory, application of targeted therapies to pre-invasive lesions will prevent their progression to invasive lesions with full malignant potential. The diagnostic challenge for pathologists is to make interpretative decisions on early detected pre-invasive lesions. Overall, only a small proportion of these pre-invasive lesions will progress to invasive carcinoma and morphological assessment is an imprecise and subjective means to differentiate histologically identical lesions with varying malignant potential. Therefore differential biomarker analysis in pre-invasive lesions may prevent overtreatment with surgery and provide a predictive indicator of response to therapy. There follows a review of established and emerging potential druggable targets in pre-invasive lesions and correlation with lesion morphology.

High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes

To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes.

Low-energy cranberry juice decreases lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome

Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 ± 0.6 to 2.2 ± 0.4 µmol/L [means ± SD], P <.05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 ± 31.0 to 80.4 ± 34.6 U/L and 3.4 ± 1.1 to 1.7 ± 0.7 µmol/L, respectively [means ± SD], P <.05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome.

Low clusterin levels in high-density lipoprotein associate with insulin resistance, obesity, and dyslipoproteinemia

To determine whether obesity and insulin resistance associate with changes in the protein content of high-density lipoprotein (HDL) in 2 different groups of men by using targeted proteomics.

Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome

Green tea (Camellia sinensis) has shown to exert cardioprotective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects.

Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes

To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress.

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.