Advances on photodynamic therapy of melanoma through novel ring-fused 5,15-diphenylchlorins.

The synthesis, photophysical behaviour and photosensitization ability of novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused 5,15-diphenylchlorins against melanoma cells are described. All studied chlorins were found to be extremely active against melanoma cell lines A375 showing IC50 values below 20 nM. Furthermore, a dihydroxymethyl diphenylchlorin was identified as an excellent candidate to allow modulating of different types of cell death, apoptosis vs. necrosis, by varying its concentration. This can be explored as a tool to improve the effectiveness of PDT since inflammatory response resulting from necrotic cell death after PDT can activate the antitumor immune response with implications also regarding the vascular damage. This feature combined with very low cytotoxicity against human melanoma cells in the absence of light activation and against human fibroblast HFF-1 cells makes this chlorin a candidate of choice as a photosensitizer for PDT. A comprehensive photophysical investigation including the determination of quantum yields for fluorescence, singlet oxygen sensitization and internal conversion, lifetimes and rate constants of all the excited state deactivation processes has been undertaken.

Longstanding spastic paraparesis in a patient infected with hepatitis C virus and seropositive for aquaporin-4 antibody - Case report and review of the literature.

Nervous system involvement in Hepatitis C virus infection (HCV) has been associated to neuro-immunological deregulation, particularly in interferon-alpha treated patients. We present a case of optic and brainstem demyelinating disorder associated with aquaporin-4 (AQP4) antibodies. A 48 year-old woman, with previous diagnosis of non-treated hepatitis C, presented with a 10-year history of long-standing gait disturbance. Neurological examination disclosed a grade 4 spastic paraparesis, lower limb hyperreflexia, right positive Hoffmann sign, bilateral Babinski sign and spastic gait only possible with bilateral support. Spinal cord magnetic resonance imaging (MRI) was normal. Brain MRI showed an asymmetric, bilateral pontine and left mesencephalic hypersignal in T2 and FLAIR, with no gadolinium enhancement. Visual evoked potential revealed bilateral pre-chiasmatic conduction delay. Blood tests showed a positive anti-HCV antibody and a positive AQP4 antibody. Cerebrospinal fluid (CSF) analysis was normal, with no oligoclonal bands. The patient started intravenous (IV) methylprednisolone followed by oral prednisolone; simultaneously, interferon-alpha and ribavirin. There was a slight clinical improvement within the first weeks. There are 7 cases describing association between HCV infection and central nervous system (CNS) demyelination with positive AQP4 antibody, 4 patients under interferon-α. AQP4 antibodies should be tested in patients infected with HCV and CNS demyelination.