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Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p < 0.0001, ANOVA test followed by Tukey’s multiple comparisons test), suggesting that both PTN and PTN-PDT would be potential inhibitors of metastasis. Fluorescence microscopy observation indicated cytoplasmic localization of the AQ and no fluorescence at all was recorded in the nuclei. When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28% both on days 3 and 4 of the experiment (*p < 0.05 control vs. PTN-PDT, two-way ANOVA, followed by Sidak’s multiple comparisons test). Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties. On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

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Heterophyllaea pustulata is a phototoxic plant from Argentina. Aerial parts extracts, high in photosensitizing anthraquinones, have shown in vitro antiviral activity. The purpose of this study was to study the antiherpetic activity of the main purified anthraquinones, even evaluating their competence as photodynamic sensitizers to photo-stimulate the antiviral effect. In vitro antiviral activity against Herpes Simplex virus type I and the photo-inactivation of viral particle were studied by the Neutral Red uptake test and observation of the cytopathic effect. Rubiadin 1-methyl ether and 5,5′-bisoranjidiol produced a significant effect (≥ 80% inhibition) with minimal damage to host cells (subtoxic concentration). Anthraquinones with poor antiherpetic activity at its maximum noncytotoxic concentration showed an important photo-stimulated effect, such is the case of soranjidiol and 5,5′-bisoranjidiol (28.0 ± 6.3 vs. 81.8 ± 2.1% and 15.5 ± 0.3 vs. 89.8 ± 1.7%, respectively). The study also proved the decrease of viral particles, necessary to reduce infection. Therefore, photosensitizing anthraquinones from natural resources could be proposed to develop new treatments for localized viral lesions with antimicrobial photodynamic therapy.

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BackgroundChagas disease (CD) is an endemic and neglected infection in Latin America. Due to international human migration, it has become a worldwide issue. Scarce evidence is published regarding its behavior in rheumatic diseases (RD) with rheumatologic treatments (RT).ObjectivesTo screen and follow up patients with CD under RT. To detect clinical and serological reactivation.MethodsA systematic screening was conducted between January 2018 and January 2019 in a third-level Hospital in Argentina. Patients with CD and concomitant RD under RT were included. Assessments were done before and after RT. A direct (Strout) and indirect method (Polymerase chain reaction-PCR) were performed in order to detect parasitemia, levels of antibodies were evaluated by three techniques. Clinical, infectological and cardiological features were examined. Everything was assessed in, at least, two opportunities, separated by a minimum of one month. If treatment was modified or clinical condition changed, all the evaluations were repeated as before. In case of reactivation, specific treatment was indicated and follow up controls were stricter.Results38 patients were identified. RD: Rheumatoid Arthritis: 22 (57,9%), Systemic lupus erythematosus: 4 (10,5%), Systemic Sclerosis: 3 (7,9%), Vasculitis: 2 (5,3%), Psoriatic Arthritis: 1 (2,6%), others: 6 (15,8%). RT: classic, synthetic and biological disease-modifying antirheumatic drugs, cyclophosphamide and corticosteroids.Two reactivations were detected with both direct and indirect methods, with a significant title antibody increment and consistent clinical signs and symptoms. Cardiological abnormalities were found. A 64-years old lady with Microscopic Polyangiitis, under prednisone 60 mg/day and a 57-years old lady with Systemic Lupus Erythematosus under hydroxychloroquine and prednisone 40 mg/day, who happen to be sisters. They did not have other treatments. Both of them developed high fever, myalgias, arthralgias and asthenia. Other infections were ruled out. They received Benznidazole and Nifurtimox respectively. After one-week treatment, Strout and PCR became negative and antibodies decreased, with remarkable clinical improvement.ConclusionTwo patients with parasitemia and concomitant symptoms were detected, after high doses of corticosteroids. Because they were sisters, a genetic background would also play a role. Parasite’s screening before starting immunosuppression and its follow-up during treatment in search of reactivation should be integrated to rheumatology daily practice in endemic countries. It should also be taken into account in patients from non-endemic countries that have an epidemiological nexus. CD specific antibodies determination, Strout and PCR are economic and practical techniques, although they require qualified personnel and equipment. In areas with high prevalence of CD, the benefits of this measures would outweigh costs. A more advanced study should be performed to extend our knowledge.Disclosure of InterestsNone declared