New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series

A new highly selective inhibitor of acetylcholinesterase (AChE) was discovered by high-throughput screening. Compound 1 was synthesized from a natural product, the N-3-isobutyrylcycloxobuxidine-F 2. A new extraction protocol of this compound is described. The hemisynthesis and optimization of 1 are reported. The analogs of 1 were tested in vitro for the inhibition of both cholinesterases (AChE and BuChE). These compounds selectively inhibited AChE. Extensive molecular docking studies were performed with 2 and AChE employing Discover Biosym software to rationalize the binding interaction. The results suggested that ligand 2 binds simultaneously to both catalytic and peripheral sites of AChE.     

Testing for human papillomavirus and measurement of viral load of HPV 16 and 18 in self‐collected vaginal swabs of women who do not undergo cervical cytological screening in Southern France

Self‐sampling using vaginal swabs could be a valuable alternative to screen for cervical cancer for women who do not attend regular cytological screening. The aim of this study was to determine the prevalence of high and low‐risk HPV types and of HPV type 16 and 18 DNA load in self‐collected vaginal swabs from 35‐ to 69‐year‐old Southern French women of low socioeconomic level or migrant populations who do not attend regular cervical screening. A good concordance (93.1%) was found between cervical brush and vaginal swabs in 29 samples. Self‐collected vaginal swabs were examined from 120 women. HPV infection was found in 28 women (23.3%; median age 48 years), 17 (14.1%) of whom harbored high‐risk HPV types. HPV type 16 was the high risk type found most frequently, followed by types 53, 31, 18, 58, and 66. The low‐risk type detected most frequently was HPV type 6, followed by types 61, 70, and 81. The mean HPV 16 and 18 load was 6.3 log₁₀ copies/10⁶ cells and 2.4 log₁₀ copies/10⁶ cells, respectively. These results suggest that vaginal self‐swabs can be a reliable tool for cervical cancer screening in non‐attending and inadequately screened elderly women. J. Med. Virol. 82:1431–1437, 2010. © 2010 Wiley‐Liss, Inc.     

Long-term food-exposure of zebrafish to PCB mixtures mimicking some environmental situations induces ovary pathology and impairs reproduction ability

Although the use of polychlorinated biphenyls (PCBs) has been banned for several decades, they are still present in the environment and are occasionally mechanically released from sediment or transferred through the trophic chain. Field analyses have established correlations between exposure to PCBs and alterations in fish physiology including reproductive function. Experimental exposures have been mainly performed using dioxin-like PCBs or other congeners at very high concentrations. However, these studies are often difficult to relate to real-life conditions. In the present study, we performed a life-cycle exposure using zebrafish model and mixtures representative of some environmental situations in terms of doses, composition and containing mainly non dioxin-like congeners. Exposure was performed through diet which is the main contamination route in the field. We demonstrated a bioaccumulation of PCBs in males and females as well as a maternal transfer to the eggs. Survival, growth and organ size were similar for all conditions. Several reproductive traits were altered after exposure to a PCB-contaminated diet, including a reduction in the number of fertilized eggs per spawn as well as an increase of the number of poorly fertilized spawns. This latter observation was found irrespective of the sex of contaminated fish. This is related to modifications of ovary histology revealing a decrease of maturing follicles and an increase of atretic follicles in the ovaries of females exposed to PCBs. These results indicate that exposure to PCBs mixtures mimicking some environmental situations, including mainly non dioxin-like congeners, can lead to a dramatic reduction in the number of offspring produced by a female over a lifetime. This is of great concern for wild species living under natural conditions.     

Sexual risk factors related to lack of HIV-screening in people attending erotic industry shows

The current aim of the fight against the HIV epidemic is to reduce the proportion of missed opportunities for HIV diagnosis. Erotic industry Shows (ES) were deemed to be appropriate events to organize awareness campaigns and to propose HIV Rapid Diagnostic Test (HIV-RDT) to people who are sexually active and likely to engage in unsafe sex practices. In 2015, a cross-sectional study in 4 ES was conducted to document the sexual risk factors associated with HIV-screening test approach and the proportion of positive HIV-RDT. Prevention booths were set up to offer HIV-screening to individuals ≥18 years volunteers for HIV-RDT and to respond to a validated anonymous self-reported questionnaire. In 4 ES, 943 participants were questioned and tested, mainly men (64%), young (mean age 30 years old), living as a couple (63.7%). A large majority (95.1%) reported sexual intercourse over the last year. The mean number of partners was 4.8. About 2/3 had unprotected sex. 37.5% had never been tested and had their first test during this campaign. The 430 participants who reported no previous HIV-testing during the last 5 years more frequently declared heterosexual intercourse (OR: 2.31), identifying as a male (OR: 1.82), having transactional sex (OR: 1.92), living as a couple (OR: 1.67), having fewer sexual partners (OR: 1.06) and being younger (OR?=?1.02). Three people (0.32%) were tested positive for the HIV-RDT; linkage with care was ensured for confirmatory test. This innovative and original intervention showed for the first time the usefulness of HIV-screening and awareness campaigns, in fun and commercial backdrop event. Individuals who had never been HIV-tested and who had no intention of doing so before this campaign were reached and engaged. ES are potential new locations to get HIV information and screening, to tackle sexual health-related issues and reflect on sexual risk behaviors.     

Mast cell chymase in experimentally induced psoriasis

Mast cell chymase can have a pro‐inflammatory or an immunosuppressive function in psoriasis, but the outcome may depend on the level of chymase activity. Therefore, mast cells showing chymase activity (Chy_act) and immunoreactivity (Chy_prot) were studied during the Köbner reaction (0 days, 2 h, 1 day, 3 days and 7 days) of psoriasis induced by the tape‐stripping technique. Also, the effect of recombinant human chymase (rh‐chymase) or human LAD2 mast cells (LAD2) on the ³H‐thymidine uptake of psoriatic peripheral blood mononuclear cells (PBMC) or total T cells was studied. The Chy_act/Chy_prot ratio tended to be higher in all time‐point biopsies in the Köbner‐negative (n = 10) than ‐positive (n = 8) group (P = 0.073), although chymase activity decreased significantly at 2 h to 1 day only in the Köbner‐negative group. rh‐chymase (0.05–0.5 μg/mL) stimulated to a varying extent PBMC in eight out of nine cultures, but in all cultures 5 μg/mL rh‐chymase turned the stimulation towards inhibition. The effect of rh‐chymase on T cells varied from stimulation to inhibition, but in 11 of 15 cultures rh‐chymase, at least at 5 μg/mL, produced a change to inhibition. In co‐cultures, LAD2 inhibited PBMC in the absence of soybean trypsin inhibitor (SBTI). In the presence of SBTI, LAD2 stimulated PBMC in the majority of seven cultures. In summary, the psoriatic immunopathogenesis may be promoted at low, but controlled at high, activity status of chymase.