Bicyclo[4.4.0]decane oxygenated sesquiterpenes from Eryngium maritimum essential oil

Investigation of the essential oil of the aerial parts of Eryngium maritimum L. from Corsica led to the isolation of one known sesquiterpene (1) and three new oxygenated sesquiterpenes with a muurolane or cadinane skeleton (2-4). Structure assignments of 4 βH -muurol-9-en-15-al (1), 4 βH -cadin-9-en-15-al (2), 4 βH -muurol-9-en-15-ol (3) and 4 βH -cadin-9-en-15-ol (4) were carried out by GC/MS (EI and CI) and comprehensive 1D and 2D NMR spectroscopy. Antibacterial activity of Eryngium maritimum L. oil and column chromatography fractions have been investigated for the first time. The oxygenated fraction, which contains the four sesquiterpenes, was efficient against Listeria monocytogenes and Echerichia coli.     

Development of a miniaturized HIFU device for glaucoma treatment with conformal coagulation of the ciliary bodies

This study examined the feasibility of high-intensity focused ultrasound (HIFU) for glaucoma treatment with conformal coagulation of the ciliary bodies (CB). A miniaturized high frequency (21 MHz) device was developed, based on the geometry of the eye and adapted to the anatomy of the rabbit eyeball. Six line-focus lesions were distributed along a circle and produced by six cylindrical transducers. To be conformal, the numerical model predicted an intensity of 6.9 W/cm², with exposure duration of 3 s ON (powered per sector). In vivo experiments were conducted on two rabbits. A significant intraocular pressure reduction was noted (-45% and -31%). Histology demonstrated conformal and homogeneous coagulation of the CB without side effects. (E-mail: thomas.charrel@inserm.fr)     

News in management of colorectal cancer at JFHOD 2012 meeting

All aspects of the management of colorectal cancer were presented during the 2012 edition of JFHOD meeting, from screening to new drugs tested in metastatic situation. It was confirmed that an average number of more than 0.8 detected polyps was a quality criteria of screening colonoscopies performed for positive Hemoccult^®. The superiority of brush-sampling fecal immunological test compared to guaiac fecal occult blood test has been demonstrated in two studies, with doubled and tripled detection rates of invasive cancers and advanced adenomas, respectively. Reproducibility is a major quality factor of the histopathological analysis of malignant colorectal polyps treated by endoscopic polypectomy. The inter-observer concordance was satisfying for the invasion depth and the resection margins, but inadequate for the degree of differentiation, the budding, the degree of submucosal infiltration and vascular embol. Reliability was enhanced by the importance of the endoscopic activity in center and by the orientation of the polyps. Ultrasonographic evidence of downsizing after neoadjuvant radiochemotherapy in rectal cancer was predictive of better survival. In a randomized trial, neoadjuvant radiochemotherapy was more toxic in patients older than 70 years, inducing a decreased frequency of surgery and more frequent permanent colostomy. After retrospective analysis of individual data from patients with synchronous metastases included in four clinical trials, the resection of the primary tumor was an independent predictive factor of overall and progression free survival. A prospective randomized trial must confirm this result. A study confirmed the important contribution of diffusion-weighted MRI in the preoperative evaluation of liver metastases. Promising data were presented concerning the intensification of chemotherapy, hepatic intra-arterial chemotherapy and integration of targeted therapies to increase the resectability rate of metastases. In palliative setting, the promising action of two tyrosine kinase inhibitors (sorafenib and nintedanib) in phase I-II studies will warrant further clinical development.     

First ex vivo study demonstrating that <Superscript>99m</Superscript>Tc-NTP 15-5 radiotracer binds to human articular cartilage

Purpose  

Preclinical data pointed to ^99mTc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify ^99mTc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone ^99mTc-hydroxymethylene diphosphonate (HMDP) radiotracer.     

Residual Varus Alignment does not Compromise Results of TKAs in Patients with Preoperative Varus

Background   

Postoperative varus alignment has been associated with lower IKS scores and increased failure rates. Appropriate positioning of TKA components therefore is a key concern of surgeons. However, obtaining neutral alignment can be challenging in patients with substantial preoperative varus deformity and it is unclear whether residual deformity influences revision rates.     

Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression

Mycolactone is a macrolide produced by Mycobacterium ulcerans with immunomodulatory properties. Here, we describe that in mouse, mycolactone injection led to a massive T-cell depletion in peripheral lymph nodes (PLNs) that was associated with defective expression of L-selectin (CD62-L). Importantly, preexposure to mycolactone impaired the capacity of T cells to reach PLNs after adoptive transfer, respond to chemotactic signals, and expand upon antigenic stimulation in vivo. We found that mycolactone-induced suppression of CD62-L expression by human primary T cells was induced rapidly at both the mRNA and protein levels and correlated with the reduced expression of one miRNA: let-7b. Notably, silencing of let-7b was sufficient to inhibit CD62-L gene expression. Conversely, its overexpression tended to up-regulate CD62-L and counteract the effects of mycolactone. Our results identify T-cell homing as a biological process targeted by mycolactone. Moreover, they reveal a mechanism of control of CD62-L expression involving the miRNA let-7b.Mycolactone is a diffusible macrolide produced by Mycobacterium ulcerans, the causative agent of a chronic skin disease called Buruli ulcer (BU) (1). Mycolactone production is critical for bacterial virulence and underpins the pathogenesis of lesions marked by a striking lack of inflammatory infiltrates. The immune profiling of patients has recently revealed systemic defects in the production of multiple T-cell cytokines, suggesting that mycolactone impairs the generation of cellular responses (2). In line with this hypothesis, mycolactone was reported to suppress the production of various cytokines by monocytes, lymphocytes, and dendritic cells (DCs) in vitro (3–6). The mechanism by which mycolactone modulates protein expression in a gene- and cell-specific manner nevertheless remains mysterious, as differently from known immunosuppressants, mycolactone acts independently of the mammalian target of rapamycin (mTOR).Studies in mice have shown that s.c.-delivered mycolactone gains access to the leukocytes of the peripheral blood and lymphoid organs and triggers immune defects comparable with those observed in BU patients (7). The mouse model therefore appears appropriate to study the impact of mycolactone on cellular responses in vivo. Mycolactone blocks the maturation and migration of DCs in the mouse (5); however, whether it impairs the trafficking properties of T cells, the key players in the adaptive immune response to pathogens, is still unknown. In this process, the capacity of naive T cells to gain access to peripheral lymph nodes (PLNs) and make contact with antigen-presenting cells is of critical importance. T-cell homing to PLNs is controlled by the expression of the receptors l-selectin (CD62-L), C-C chemokine receptor 7 (CCR7), and lymphocyte function-associated antigen 1 (LFA-1). High expression of CD62-L on the surface of naive T cells is essential for the initial steps of tethering and rolling of circulating lymphocytes in the high endothelial venules (HEV) of peripheral LNs, whereas CCR7 and LFA-1 play a crucial role in the subsequent adhesion of T cells to HEV (8). Within the LNs, T cells then migrate to specialized T-cell zones, where CCR7-driven motility is vital for scanning antigens presented by DCs (9).Here, we have used a combination of transgenic mouse models, LN explants, and human primary T cells to evaluate the impact of mycolactone on T-cell dynamics. We found that s.c.-delivered mycolactone modified the expression of CD62-L, CCR7, and LFA-1 on circulating T cells. These alterations had major consequences on the capacity of T cells to home to PLNs and on the intensity of cellular responses driven by antigen. We identified the let-7b microRNA (miRNA) as a regulatory component of CD62-L expression in human T cells and provided a mechanistic explanation for how mycolactone regulates CD62-L expression by altering let-7b levels. Our results uncover a unique biological property of mycolactone through the regulation of T-cell trafficking and demonstrate that CD62-L expression is partially regulated by the let-7b miRNA.     

Psychose hystérique : solution psychotique à l’irruption de la sexualité génitale ?

The notion of hysterical psychosis implies the paradox of a psychotic genitality. Leaning on the psychoanalytic, phenomenological and gestaltist approach of Gisela Pankow, we try to define this nosographic entity, by underlining in a patient a special kind of relationship with imagos and own body we called dialectic of penetration. In that kind of pathological functioning, De Clérambault's syndrome could be understood as the realization, in the psychotic experience area, of a sort of intrusive genital sexuality, and delusion as a new performance of œdipal drama on the delusional scene. We finally question the place of a lacunar Oedipus complex in non-schizophrenic psychoses.