Sexual Functioning and Opioid Maintenance Treatment in Women. Results From a Large Multicentre Study

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men’s sexuality, the data collected about the change in women’s sexual functioning is still limited despite the fact that it is now well-known that opioids - both endogenous and exogenous - affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients’ mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants’ mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation

5,6-Dihydroxyindole Tetramers with "Anomalous" Interunit Bonding Patterns by Oxidative Coupling of 5,5',6,6'-Tetrahydroxy-2,7'-biindolyl: Emerging Complexities on the Way toward an Improved Model of Eumelanin Buildup.

Chem. or enzymic oxidn. of 5,6-dihydroxyindole (I) leads to the rapid deposition of a black solid resembling eumelanin pigments by way of a complex oligomerization/polymn. process that proceeds in the early stages via dimers and trimers characterized by 2,4'- and 2,7'-couplings. Despite extensive efforts, the structures of the higher oligomers, which define the structural architecture and physicochem. properties of the eumelanin particles, have so far defied elucidation. Using a dimer-dimer coupling strategy that has recently allowed the first successful entry to a tetramer of I, the authors report now three addnl. tetramers obtained by oxidn. of 5,5',6,6'-tetrahydroxy-2,7'-biindolyl with the peroxidase/H2O2 system. On the basis of extensive 2D NMR and mass spectrometric anal., the products were identified as acetylated II (3%), III (4%), and IV (5%), in which the inner units are linked through unexpected 3,3'-, 4,4'-, and 2,3'-linkages. If verified in further studies, the newly uncovered coupling patterns would entail important consequences for current models of eumelanin structure based on one-dimensional structural chains with extended p-electron conjugation or p-stacked flat oligomer aggregates

A novel fluoride-sensing scaffold by a peculiar acid-promoted trimerization of 5,6-dihydroxyindole

An unusual rearranged trimer, 2-(2-amino-4,5-dihydroxybenzyl)-6,7-dihydroxy-3-(5,6-dihydroxyindol-3-yl)quinoline (1a), was obtained as the acetyl deriv. (1b) by mild acid-promoted polymn. of 5,6-dihydroxyindole at pH 2. Compd. 1b proved to be a selective fluoride-sensing compd., transducing F- binding into a distinct absorption at 414 nm and a marked fluorescence enhancement at 489 nm

Eumelanin Buildup on the Nanoscale: Aggregate Growth/Assembly and Visible Absorption Development in Biomimetic 5,6-Dihydroxyindole Polymerization

Establishing structure-property relationships in the black insoluble eumelanins, the key determinants of human pigmentation and skin photoprotective system, is a considerable conceptual and experimental challenge in the current drive for elucidation of the biological roles of these biopolymers and their application as advanced materials for organoelectronics. Herein, we report a new breakthrough toward this goal by the first detailed investigation on the nanoscale level of the oxidative polymerization of 5,6-dihydroxyindole (DHI), a model process of eumelanin synthesis. On the basis of a combined use of spectrophotometry, dynamic light scattering (DLS), and small-angle neutron scattering (SANS) investigations, it was possible to unveil the dynamics of the aggregation process before precipitation, the key relationships with visible light absorption and the shape of fundamental aggregates. The results indicated a polymerization mechanism of the type: Polymer(n) + DHI(x) = Polymer(n+x), where DHI(x) indicates monomer, dimer, or low oligomers (x ≤ 5). During polymerization, visible absorption increases rapidly, reaching a plateau. Particle growth proceeds slowly, with formation of 2-D structures ~55 nm thick, until precipitation occurs, that is, when large aggregates with a maximum hydrodynamic radius (R(h)) of ~1200 nm are formed. Notably, markedly smaller R(h) values, up to ~110 nm, were determined in the presence of poly(vinyl alcohol) (PVA) that was shown to be an efficient aggregation-preventing agent for polymerizing DHI ensuring water solubilization. Finally, it is shown that DHI monomer can be efficiently and partially irreversibly depleted from aqueous solutions by the addition of eumelanin suspensions. This behavior is suggested to reflect oxidant-independent competing pathways of polymer synthesis and buildup via monomer conversion on the active aggregate surface contributing to particle growth. Besides filling crucial gaps in DHI polymerization, these results support the attractive hypothesis that eumelanins may behave as a peculiar example of living biopolymers. The potential of PVA as a powerful tool for solution chemistry-based investigations of eumelanin supramolecular organization and for technological manipulation purposes is underscored

Structural effects on the electronic absorption properties of 5,6-dihydroxyindole oligomers: the potential of an integrated experimental and DFT approach to model eumelanin optical properties

Elucidation of the relations between structural features and UV-visible absorption properties of 5,6-dihydroxyindole oligomers is an essential step towards an understanding of the unique optical properties of eumelanins. Herein, the authors report the first combined exptl. and d. functional theory (DFT) study of the 5,6-dihydroxyindole oligomers so far isolated. 2,2'-Biindolyl 2 and the 2,4'-biindolyl 3 absorb at longer wavelengths relative to 2,7'-biindolyl 4 and their spectra were well predicted by DFT anal. The absorption bands of 2,4':2',4''- and 2,4':2',7''-triindolyls 5 and 6 also fall at different wavelengths and can be interpreted by DFT simulations as being due to a combination of two main sep. transitions. Tetramer 7, in which two 2,4'-biindolyl units are linked through a 2,3'-connection, exhibits a broad chromophore extending over the entire UV range without well defined absorption maxima. Within the dimer-tetramer range examd., three key points emerge: (1) an increase in oligomer chain length does not result in any regular and predictable bathochromic shift; (2) a marked broadening of the absorption bands occurs when going from the monomer to the tetramer structure; and (3) the mode of coupling of the indole units is a crucial, hitherto unrecognized, structural parameter affecting the electronic absorption properties of 5,6-dihydroxyindole oligomers. Use of exptl. characterized oligomeric scaffolds as a basis for DFT calcns. is a most promising approach to building reliable structural models for studies of eumelanins optical properties

Cyclic Structural Motifs in 5,6-Dihydroxyindole Polymerization Uncovered: Biomimetic Modular Buildup of a Unique Five-Membered Macrocycle

An unprecedented 5,6-dihydroxyindole macrocycle I featuring a rigid twisted backbone was obtained by biomimetic oxidative cross-coupling of the 2,2'-biindole II and triindole III. A putative reaction intermediate, 2-quinone IV, was detected and characterized by pulse radiolysis and DFT calcns. Discovery of I indirectly supports for the first time theor. predicted cyclic structural motifs as potential eumelanin building blocks