From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs

Monoamine oxidases (MAOs) are well-known pharmacological targets in neurological and neurodegenerative diseases. However, recent studies have revealed a new role for MAOs in certain types of cancer such as glioblastoma and prostate cancer, in which they have been found overexpressed. This finding is opening new frontiers for MAO inhibitors as potential antiproliferative agents. In light of our previous studies demonstrating how a polyamine scaffold can act as MAO inhibitor, our aim was to search for novel analogs with greater inhibitory potency for human MAOs and possibly with antiproliferative activity. A small in-house library of polyamine analogs (2-7) was selected to investigate the effect of constrained linkers between the inner amine functions of a polyamine backbone on the inhibitory potency. Compounds 4 and 5, characterized by a dianiline (4) or dianilide (5) moiety, emerged as the most potent, reversible, and mainly competitive MAO inhibitors (Ki < 1 μM). Additionally, they exhibited a high antiproliferative activity in the LN-229 human glioblastoma cell line (GI50 < 1 μM). The scaffold of compound 5 could represent a potential starting point for future development of anticancer agents endowed with MAO inhibitory activity

Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10−04) and rs8099917 (P value = 5.5 × 10−04). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10−05). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10−04). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917

Performance evaluation of the coastal aerosol extinction code MEDEX with data from the Black Sea,

Validation of the aerosol model MEDEX in the Black Se

Development of the Mediterranean extinction code MEDEX

Development of the coastal aerosol model, MEDEX

An extension of the Navy Aerosol Model (NAM) to coastal areas

Development of a coastal model for aerosol size distribution

A rare case of extrauterine adenosarcoma arising in endometriosis of the rectovaginal septum

Objective: To present a rare case of endometrial stromal sarcoma arising in endometriosis of the rectovaginal septum. Design: Case report. Setting: Academic tertiary referral center for endometriosis treatment. Patient(s): A 50-year-old woman with a history of endometriosis presented with catamenial rectal pain and deep dyspareunia. Imaging findings suggested new endometriotic lesions in the rectovaginal space. Intervention (s): Total hysterectomy, salpingo-oophorectomy, and excision of the lesion in the rectovaginal septum were performed. Although extemporary pathology confirmed endometriosis, the final histologic diagnosis was extrauterine adenosarcoma in the rectovaginal septum. Two years later, recurrence of the malignancy occurred and was treated by resecting the new perirectal mass. Subsequent radiotherapy and chemotherapy were administered. Main Outcome Measure(s): Imaging findings at follow-up evaluation. Result(s): The patient was in good health for 2 years after the initial surgery, when she developed a new lesion at the site of the previous resection. The histologic appearance of the lesion was consistent with recurrence of the tumor. After postoperative therapy, the patient is now without evidence of disease. Conclusion(s): Malignant transformation of endometriosis should be considered in the differential diagnosis of a new pelvic lesion in a patient with a history of endometriosis

Aerosol extinction in coastal zone

The performance of electro-optical systems can be substantially affected by aerosol particles that scatter and absorb electromagnetic radiation. A few years ago, an empirical model was developed describing the aerosol size distributions in the Mediterranean coastal atmosphere near Toulon (France). This model has been coupled with Mie theory to yield the code MEDEX (MEDiterranean Extinction) for the aerosol extinction. This contribution deals with the evaluation of MEDEX for aerosol data recorded near the Black Sea coast. For this site, MEDEX correctly predicts the aerosol extinction as function of wavelength, albeit with minor discrepancies below one micron. These differences are attributed to the uncertainty in predicting the concentrations of submicron particles. The comparison shows that MEDEX may be more generally applicable than to the Toulon area

A rare case of extrauterine adenosarcoma arising in endometriosis of the rectovaginal septum

malignant transformation of endometriosis should be considered in the differential diagnosis of a new pelvic lesion in a patient with a history of endometriosi