Alain Guillet

Agents Blocking the Nuclear Factor-κB Pathway Are Effective Inhibitors of Endometriosis in an in vivo Experimental Model

Background: In vitro studies suggest that the transcription factor nuclear factor-kappa B (NF-ĸB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement of NF-ĸB and the processes regulated by NF-ĸB in the initial development of endometriotic lesionsin vivo.Methods: Endometriosis was induced in nude mice by intraperitoneal injection of fluorescent-labeled menstrual endometrium. Two NF-ĸB inhibitors (BAY 11-7085 and SN-50) were injected intraperitoneally on days 0, 2 and 4 after endometriosis induction, and endometriotic lesions were recovered on day 5. Number, mass, fluorimetry and surface (morphometry) of endometriotic lesions were quantified. NF-ĸB activation, intercellular adhesion molecule (ICAM)-1 expression, cell proliferation and apoptosis were evaluated by immunohistochemical analyses and the TUNEL method. Results: Both NF-ĸB inhibitors induced a significant reduction in lesion development compared to control mice. NF-ĸB activation and ICAM-1 expression of endometriotic lesions were significantly reduced in treated mice, and cell proliferation was significantly reduced in BAY 11-7085-treated mice. Both inhibitors produced a significant increase in apoptosis of endometriotic lesions, as assessed by active caspase-3 immunostaining and the TUNEL method. Conclusion: This study demonstrates, for the first time, that the NF-ĸB pathway is implicated in the development of endometriotic lesions in vivo and that NF-ĸB inhibition reduces ICAM-1 expression and cell proliferation, but increases apoptosis of endometriotic lesions, diminishing the initial development of endometriosis in an animal model.

Supramolecular Organization in Organic–Inorganic Heterogeneous Hybrid Catalysts Formed from Polyoxometalate and Poly(ampholyte) Polymer

Hybridization of polyoxometalates (POMs) via the formation of an organic-inorganic association constitutes a new route to develop a heterogeneous POM catalyst with tunable functionality imparted through supramolecular assembly. Herein, we report on strategies to obtain tunable well-defined supramolecular architectures of an organic-inorganic heterogeneous hybrid catalyst formed by the association of a hydrophobically substituted polyampholyte copolymer (poly N, N-diallyl-N-hexylamine-alt-maleic acid) and phosphotungstic acid (H3PW12O40) POMs. The self-assembling property of the initial polyampholyte copolymer matrix is modulated by controlling the pH of the hybridization solution. When deposited on a mica surface, isolated, long and extended polymer chains are formed under basic conditions (pH 7.9), while globular or coiled structures are formed under acidic conditions (pH 2). The supramolecular assembly of the POM-polymer hybrid is found to be directed by the type and quantities of charges present on the polyampholyte copolymer, which themselves depend on the pH conditions. The hypothesis is that the Keggin type [PW12O40](3-) anions, which have a size of ~1 nm, electrostatically bind to the positive charge sites of the polymer backbone. The hybrid material stabilized at pH 5.3 consists of POM-decorated polymer chains. Statistical analysis of distances between pairs of POM entities show narrow density distributions, suggesting that POM entities are attached to the polymer chains with a high level of order. Conversely, under acidic conditions (pH 2), the hybrid shows the formation of a core-shell type of structure. The strategies reported here, to tune the supramolecular assembly of organic-inorganic hybrid materials, are highly valuable for the design and a more rational utilization of POM heterogeneous catalysts in several chemical transformations.

Involuntary commitment in psychiatric care: what drives the decision?

BackgroundPsychiatric commitment laws have been reformed in many European countries. We assessed the relative importance of the different legal criteria in explaining involuntary commitment under the Belgian Mental Health Act of 1990.MethodPsychiatric assessments were requested for 346 patients living in Brussels who were randomly selected from a larger group and were being considered for involuntary commitment. A retrospective study of these patients’ files was carried out.ResultsMore than half of the requests for involuntary commitment were turned down. The lack of a less restrictive alternative form of care was the criterion most crucial in decisions in favour of commitment. Alternative forms of care were more likely to be unavailable for psychotic individuals, foreigners, and patients not living in a private household.ConclusionInvoluntary commitment is mainly due to the inability of the mental health care system to provide more demanding patients with alternative forms of care.

Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions.

Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images.

Oral health determinants and caries outcome among non-privileged children

The study aimed at identifying oral health determinants that are present in early childhood, are amenable to change and for which there is evidence of their modulation of the rate of caries progression in a sample of non-privileged children. The null hypothesis was that determinants associated with the childs institutional environment as evidenced by nursery policies significantly influenced the childs oral health. The sample was formed by 2,511 Brazilian 1-5-year-olds. Caries severity and activity were recorded. Parents were interviewed and nurseries answered a questionnaire. According to the case status d1efs, the final multilevel model (generalized linear mixed model) identified significant associations with determinants such as bottle-feeding the child during the night on demand, not assisting the child in toothbrushing, ensuring visit to the dentist in case of troubles with teeth only (p < 0.0001) and intake of sugary products 2-4 times daily at nursery (p = 0.026). The likelihood of caries outcomes was associated with determinants related to nursery policies, not promoting preventive oral health care for children of mothers with 4 years of education (OR = 2.14; p < 0.0015) and <4 years of education (OR = 2.6; p = 0.0010), as well as consumption of sugary products 2-4 times daily for children of mothers with 4 years of education (OR = 3.35; p = 0.0010) and <4 years of education (OR = 4.07; p = 0.0063). In conclusion, determinants related to parental negative practices and to nursery policies significantly influenced childrens oral health. Of particular interest was the identification of determinants considered amenable to change in connection with nursery policies towards oral health.

Contents Vol. 48, 2014

384 61st ORCA Congress July 2–5, 2014, Greifswald, Germany (available online only) No. 6