Successful use of tralokinumab for the treatment of atopic dermatitis on the genitals.

BACKGROUND: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area. OBJECTIVE: to evaluate the efficacy of tralokinumab in AD patients with genital involvement. METHODS: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16. RESULTS: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores. CONCLUSION: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

Penile Lichen Sclerosus Treated with 1927 nm Thulium Fiber Laser and Photodynamic Therapy: A New Possible Therapeutic Approach.

OBJECTIVE: We treated two patients with recalcitrant lichen sclerosus (LS) of the penis with a combination of 1927 nm thulium fiber laser and methyl-aminolevulinate (MAL) photodynamic therapy (PDT). BACKGROUND DATA: Therapy of LS is based on topical potent steroids, emollients, and topical calcineurin inhibitors. Circumcision is effective, but not always accepted. PDT represents a valid therapeutic option in refractory cases, but there are no reports about the association with 1927 nm thulium laser in the treatment of this pathology. MATERIALS AND METHODS: We used to treat the affected areas with a combination of 1927 nm thulium fiber laser and MAL PDT in the same section. The same protocol was repeated after 1 month. RESULTS: An improvement of lesions after the first treatment and complete cleaning after 3 months of therapy were noted. Results were maintained in the follow-up after 2 years. CONCLUSIONS: Association with 1927 nm thulium laser was able to amplify the effectiveness of PDT and to promote tissue remodeling. Despite the positive response to our case, clinical studies are lacking and further analysis could be performed on a wider population to better define correct dosage and safety profile. Further, it is necessary to compare this procedure with other treatments to establish the real effectiveness.

Zoon's balanitis successfully treated with photodynamic therapy: Case report and literature review.

Zoon's balanitis (ZB) is an idiopathic chronic condition usually presenting as a solitary erythematous plaque on the glans of primarily uncircumcised, middle-aged to older men. The different treatment options for this condition often achieve partial results, with frequent recurrence after treatment withdrawal. Recently, photodynamic therapy (PDT) has been proposed as therapeutic option with discordant results. We treated a thirty-five year-old man affected by Zoon's balanitis, resistant to conventional treatments, with 3 sessions of topical ALA-PDT at two weeks intervals. At the end of the treatment period notable improvement of clinical features was observed, with almost complete clearance at 3 months' follow-up, high safety profile and absence of durable side-effects.

New inhibitors of dihydroorotate dehydrogenase (DHODH) based on the 4-hydroxy-1,2,5-oxadiazol-3-yl (hydroxyfurazanyl) scaffold.

Based on some structural analogies with leflunomide and brequinar, two well-known inhibitors of dihydroorotate dehydrogenase (DHODH), a new series of products was designed, by joining the substituted biphenyl moiety to the 4-hydroxy-1,2,5-oxadiazol-3-yl scaffold through an amide bridge. The compounds were studied for their DHODH inhibitory activity on rat liver mitochondrial/microsomal membranes. The activity was found to be closely dependent on the substitution pattern at the biphenyl system; the most potent products were those bearing two or four fluorine atoms at the phenyl adjacent to the oxadiazole ring. A molecular modeling study suggested that these structures might have a brequinar-like binding mode. The greater potency of fluorinated analogs may depend partly on enhanced interactions with the hydrophobic ubiquinone channel, and partly on the role of fluorine in stabilizing the putative bioactive conformation.

4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues.

In order to investigate the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as a carboxylic acid bioisoster at ionotropic glutamate receptors (iGluRs), a series of acidic alpha-aminocarboxylic acids in which the distal carboxy group was replaced by the 4-hydroxy-1,2,5-oxadiazol-3-yl group was synthesized. Ionization constants were determined. All target compounds, except the Asp analogue 12, were resolved using chiral HPLC. Whereas 12 showed good affinity exclusively at NMDA receptors, the Glu analogue, (+)-10, was an unselective, though potent AMPA receptor preferring agonist (EC(50) = 10 microM at iGluR2) showing only low stereoselectivity. The two higher Glu homologues, (+)-15 and (+)-18, turned out to be weak agonists at iGluR2 as well as weak antagonists at NR1/NR2A, whereas the corresponding (-)-isomers were selective NR1/NR2A antagonists with somewhat higher potency. The results proved the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety to be a useful bioisoster at all three classes of iGluRs, capable of being integrated into agonists as well as antagonists.