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.
Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C) is a new acute-onset systemic inflammatory disease, which mainly affects children. Latent tuberculosis infection (LTBI) is characterized by the presence of immune sensitization to Mycobacterium tuberculosis (MTB) in the absence of any clinical or radiological evidence of active disease. We present a child with MIS-C related to COVID-19, with latent TB in the bone marrow, and satisfactory response to tocilizumab. It is important to pay attention in the investigation of TB cases in countries with a high prevalence of tuberculosis, especially when opting for immunusuppression.
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.
BackgroundAccording to different international registries, the frequency of use of biological agents in monotherapy in RA ranges from 12 to 39%. Targeted synthetic DMARDs (tsDMARDs-Jaki) have shown great efficacy when used as monotherapy. The rationale for this study is based on the fact that the frequency has increased with the appearance of the Jaki.ObjectivesTo estimate the frequency and reason of the use of biological drugs (bDMARDs) or tsDMARDs in monotherapy since 2013 (Year the Jaki were available in Argentina). To describe the frequency of monotherapy by treatment class and analyze the differential characteristics.MethodsRetrospective and cross-sectional multicenter study (10 reference centers from Argentina). Consecutive patients, ≥18 years, diagnosis of RA (ACR / EULAR 2010), who were under treatment with bDMARDs or tsDMARDs, started after 2013. Socio-demographic, disease and therapeutic data were collected.Statistical analysisdescriptive statistics, Chi2 test, Fisher’s exact test, Student’s T test and Mann Whitney were performed, according to the nature of the variables. A p <0.05 was considered significant.ResultsTotal 505 patients were included, 87.7% women, with a mean age 58 years (SD ± 13.5) and disease duration of 13 years (SD ± 7.8). Treatment: TNF blocker 42.1%, JAKi 30.3%, IL-6 blocker 10.9% and other treatments 16.8%.Since 2013, the frequency of monotherapy was 49% (95% CI: 45-53), in the last visit the current frequency was 41% (95% CI 37-45),of this 40% received JAKi. JAKi and IL-6 blocker were the treatments that were used more frequently in monotherapy vs combination modality (Figure 1).Figure 1.The main causes of monotherapy were intolerance (39.9%), adverse event (22%), physician’s decision (20.2%) and lack of adherence (17.7%) to DMARDs. Patients who were active workers (64% vs 55%, p <0.05), with higher socioeconomic status (31.4% vs 17.2% p <0.01), better mean HAQ at diagnosis (1.1 vs 1.3, p <0.05) an association was observed with monotherapy. In addition, an association was observed with the use of monotherapy in patients in the 2nd biological line or higher vs 1st line (53% vs 33%, p <0.01), lower polypharmacy (45.6% vs 60%, p <0.02) and a shorter mean time of biological treatment (47 months vs 39 months, p <0.01). These variables were entered in a logistic regression model, the results of the independently associated variables are shown in Table 1.Table 1.VariablepORCI 95%Employment status (active).0,1911,3270,8682,029Socioeconomic level (medium-high stratum)0,0022,151,3233,494HAQ at diagnosis, M (SD)0,0190,7040,5240,944First Line of biological treatment or Jaki (yes)0,020,4590,30,7Polypharmacy (>4 drugs) (yes)0,0180,6030,3950,918bDMARDs or tsDMARDs exposure time (months)0,0540,9940,9871ConclusionThe frequency of monotherapy, since the Jaki’s emergence, was 49% (all follow-up) and 41% (current-last visit). Intolerance to cDMARDs doctor and the patient decision were the main cause. The monotherapy use pattern was greater in those who received JAKi and anti IL6. The use of monotherapy was associated with work activity, socioeconomic status, and functional capacity at diagnosis. An association was also observed with less polypharmacy.References[1]Smolen JS, et al. Ann Rheum Dis 2020;79:685–699.[2]Emery P, Sebba A, Huizinga TW. Ann Rheum Dis.2013;72(12):1897–904.[3]F. Sommerfleck et al. Rev Arg Reumatol. 2013;24(4): 30-36[4]Aletaha D, Neogi T, Silman AJ,et al. Arthritis Rheum 2010. 2010;62(9):2569–81.Disclosure of InterestsRodrigo Garcia Salinas Speakers bureau: Abbvie, Lilly, BMS, Jassen, Novartis, boehringer ingelheim, Consultant of: Lilly, Jassen, Grant/research support from: Abbvie, Fernando Sommerfleck Speakers bureau: Abbvie, Janssen, Novartis, Grant/research support from: Abbvie, Alfredo Vargas Caselles: None declared, Luis Palomino Romero: None declared, Javier Rosa: None declared, Mariana Benegas: None declared, Etel Saturansky: None declared, Pamela Giorgis: None declared, Florencia Martinez: None declared, Marcelo Abdala: None declared, Jimena Sanchez Alcover: None declared, Emma Estela Civit De Garignani: None declared, Gabriela Vanesa Espasa: None declared, Verónica Inés Bellomio: None declared, Juan Manuel Bande: None declared, Silvia Papasidero: None declared, Veronica Saurit: None declared, Leticia Ibañez Zurlo: None declared, Emilio Buschiazzo: None declared
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