One-Pot Synthesis of Strong Anionic/Charge-Neutral Amphiphilic Block Copolymers.

Despite the ever more versatile polymerization techniques that are becoming available, the synthesis of macromolecules with tailored functionalities can remain a lengthy endeavor. This becomes more conspicuous when the implementation of incompatible chemistries (i.e., strong polyelectrolytes) within sequence-controlled polymers is desired, often requiring (i) polymerization, (ii) chain extension, and (iii) postpolymerization modification. Herein, we explore the production of strong anionic/charge-neutral block copolymers (BCPs) in a one-pot fashion. This straightforward three-step process includes the synthesis of a macroinitiator and chain extension via rapid and efficient photomediated atom transfer radical polymerization, followed by in situ deprotection to expose the polyanionic domains. The resulting BCPs, which are strong amphiphiles by nature, are capable of self-assembly in aqueous media, as evidenced by dynamic light scattering, small-angle X-ray scattering, ζ-potential measurements, and transmission electron microscopy. We further demonstrate the versatility of our methodology by producing several BCPs through sampling of a single reaction mixture, enabling the straightforward production of strong polymer amphiphiles.

Efficacy of vaginal danazol treatment in women with recurrent deeply infiltrating endometriosis.

OBJECTIVE: To describe a safe long-term medical treatment for deeply infiltrating endometriosis, a critical condition characterized by multiple painful symptoms and a high recurrence rate after surgical treatment. DESIGN: Prospective study. SETTING: University of Siena. PATIENT(S): Twenty-one women with deeply infiltrating endometriosis. INTERVENTION(S): In a nonrandomized prospective study a low dose of vaginal danazol (200 mg/d) was self-administered for 12 months. After a previous laparoscopic surgery, these patients had reported recurrent severe dyspareunia, dysmenorrhea, and pelvic pain (in five cases also painful defecation). MAIN OUTCOME MEASURE(S): Before and every 3 months during the treatment a visual analogue pain scale was used. Transvaginal and transrectal ultrasound examinations were performed before and after 6 and 12 months of treatment. Adverse effects were registered, and serum concentration of cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glycemia, protein S, protein C, antithrombin III, and homocysteine was evaluated before and after 12 months. RESULT(S): Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased within 3 months and disappeared after 6 months of treatment, with a persistent effect during the 12 months of treatment. A relief of painful defecation was also shown. Ultrasound examination showed a reduction of the nodularity in the rectovaginal septum within 6 months. The medical treatment did not affect metabolic or thrombophilic parameters; few local vaginal adverse effects were reported. CONCLUSION(S): Vaginal danazol resulted in effective medical treatment for the various painful symptoms in women with recurrent deeply infiltrating endometriosis, and because of the lack of significant adverse effects it may be proposed as an alternative to repeated surgery.

Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma.

OBJECTIVE: Activin A is a multifunctional growth and cell differentiation factor produced by normal endometrium, and secreted in high amounts by endometrial adenocarcinoma. In the present study we evaluated the expression of two inhibitory activin A ligands, follistatin and follistatin-related gene (FLRG), in endometrial adenocarcinoma and in age-matched healthy human endometrium. DESIGN AND METHODS: Atropic menopausal (n=13) and tumoral (n=9 adenocarcinoma) tissues were processed to evaluate mRNA expression levels (by semiquantitative RT-PCR) and peptide localization (by immunohistochemistry). Differences were evaluated by the unpaired t-test and assumed to be statistically significant when P<0.05. RESULTS: Both control and tumoral endometrial samples express and localize follistatin and FLRG. However, whereas follistatin mRNA expression did not differ significantly, FLRG was significantly lower in endometrial adenocarcinoma than in healthy endometrial specimens (P<0.0001). With respect to the localization of proteins, follistatin was immunolocalized in endometrial epithelial and vascular cells both in tumoral and healthy endometrium without any significant difference in intensity. Nuclear and cytoplasmic FLRG immunolocalization was seen in glands, and only nuclear immunolocalization was found in stroma and vessels of healthy endometrium. FLRG was weakly immunostained in endometrial adenocarcinoma. CONCLUSIONS: Whilst follistatin expression is unchanged, FLRG is down-regulated in endometrial carcinoma. As activin A is a differentiation factor of human endometrium, the present findings support an imbalance between increased activin A and decreased FLRG expression in endometrial cancer, so that the failure of the activin A pathway through FLRG may be pivotal in endometrial tumorigenesis.