OXavidin for Tissue Targeting Biotinylated Therapeutics

Avidin is a glycoprotein from hen egg white that binds biotin with very high affinity. Here we describe OXavidin, a product containing aldehyde groups, obtained by ligand-assisted sugar oxidation of avidin by sodium periodate. OXavidin chemically reacts with cellular and tissue proteins through Schiff's base formation thus residing in tissues for weeks while preserving the biotin binding capacity. The long tissue residence of OXavidin as well as that of OXavidin/biotinylated agent complex occurs in normal and neoplastic tissues and immunohistochemistry shows a strong and homogenous stromal localization. Once localized in tissue/tumor, OXavidin becomes an “artificial receptor” for intravenous injected biotin allowing tumor targeting with biotinylated therapeutics like radioisotopes or toxins. Moreover, present data also suggest that OXavidin might be useful for the homing of biotinylated cells. Overall, OXavidin exhibits a remarkable potential for many different therapeutic applications

The Rheumatology drugs for COVID-19 management: Which and when?

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patient

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study

Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA)

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study (2023-02-07)

Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann–Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804–0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883–0.939; p < 0.01). Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA

Propylthiouracil Is Teratogenic in Murine Embryos

Background: Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. Methods: We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. Results: When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss o