A screening of antineoplastic drugs for acute myeloid leukemia reveals contrasting immunogenic effects of etoposide and fludarabine

Background: Recent evidence demonstrated that the treatment of acute myeloid leukemia (AML) cells with daunorubicin (DNR) but not cytarabine (Ara-C) results in immunogenic cell death (ICD). In the clinical setting, chemotherapy including anthracyclines and Ara-C remains a gold standard for AML treatment. In the last decade, etoposide (Eto) and fludarabine (Flu) have been added to the standard treatment for AML to potentiate its therapeutic effect and have been tested in many trials. Very little data are available about the ability of these drugs to induce ICD. Methods: AML cells were treated with all four drugs. Calreticulin and heat shock protein 70/90 translocation, non-histone chromatin-binding protein high mobility group box 1 and adenosine triphosphate release were evaluated. The treated cells were pulsed into dendritic cells (DCs) and used for in vitro immunological tests. Results: Flu and Ara-C had no capacity to induce ICD-related events. Interestingly, Eto was comparable to DNR in inducing all ICD events, resulting in DC maturation. Moreover, Flu was significantly more potent in inducing suppressive T regulatory cells compared to other drugs. Conclusions: Our results indicate a novel and until now poorly investigated feature of antineoplastic drugs commonly used for AML treatment, based on their different immunogenic potential

Multiplicação in vitro de segmentos apicais caulinares de segurelha (Satureja hortensis L.)

O presente estudo teve por objetivo avaliar o efeito de BAP, na presença e ausência de ANA, sobre a multiplicação in vitro de segmentos apicais caulinares de Satureja hortensis. Os explantes foram isolados de plântulas germinadas in vitro e cultivados em meio nutritivo MS. O delineamento experimental utilizado foi o inteiramente casualizado, em esquema fatorial 2x5, correspondendo às concentrações de ANA (0 e 1 µM) e de BAP (0; 5; 10; 15 e 20 µM), com seis repetições, cada uma composta por três explantes. Para a porcentagem de explantes com brotações houve efeito significativo para o fator BAP, aumentando à medida que cresce a concentração da citocinina. A variável "número de brotos por explante" apresentou interação entre os fatores, havendo a maior formação de brotos na presença de ANA na faixa de 10 - 15 µM de BAP. Na presença da auxina, o maior valor ocorreu com 15 µM de BAP tendendo a diminuir independente da presença de ANA. O enraizamento dos segmentos apicais foi maior na presença de ANA e ausência de BAP, diminuindo com o aumento da citocinina. O número de folhas foi influenciado pela maior concentração de BAP sendo que a 15 µM foi observado o maior número, tendendo à queda com aumento da concentração. A concentração de 15 µM de BAP, independente de ANA, proporcionou os melhores resultados na multiplicação da espécie produzindo aumento de brotações e número de folhas, à exceção do enraizamento que foi influenciado pela auxina

Sulfated glycosaminoglycan-based block copolymer: preparation of biocompatible chondroitin sulfate-b-poly(lactic acid) micelles

International audienc

Off-label prescription of psychotropic medications in a sample of Italian psychiatrists working in private practice: A cross sectional study

Background Off-label prescription refers to the use of a drug outside the terms of its Marketing Authorization. According to the literature, this practice is particularly common in clinical psychiatry. Objective To describe patterns of off-label prescription in a sample of Italian psychiatrists working in private practice. Methods An ad hoc questionnaire was developed and sent by e-mail to a sample of Italian psychiatrists working in private practice in the Region Emilia-Romagna. The questionnaire assessed frequency of off-label prescription, reasons associated with it, diagnostic categories more often associated with such practice, main sources of information used to support off-label prescription, and psychotropic agents most commonly prescribed off-label, as well as medical-legal implications. Data were analysed by means of univariate and multivariate ordered logistic regressions. Results Fifty psychiatrists (female: 44%) out of 129 who received the e-mail invitation responded (response rate: 39%). Off-label prescription was found to be inversely proportional to clinicians' age (OR = 10.53 [95% CI 2.13-52.13]). Most commonly, second-generation antipsychotics (SGAs) were prescribed to patients diagnosed with personality disorders (PDs) (OR = 0.08 [95% CI 0.02-0.36]). A higher rate of off-label prescription was also associated to relying more on pharmaceutical sales representatives (OR = 0.58 [95%CI 0.01-0.30]) or personal professionals' clinical experience (OR = 0.05 [95% CI 0.01-0.36]) and less on other colleagues' experience (OR = 11.80 [95% CI 4.16-33.50]) as source of information. Conclusions Off-label prescription is common, especially among young psychiatrists, who frequently rely on previous personal clinical experience, especially when prescribing SGAs for treating patients with PDs. Respondents pointed to the need for further research and training on the topic addressed by the present study

ViCe: a VIrtual CEll

We report on the specification and analysis of VICE, a hypothetical cell with a genome as basic as possible. We used an enhanced version of the π-calculus and a prototype running it to study the behaviour of VICE. The results of our experimentation in silico confirm that our virtual cell “survives” in an optimal environment and shows a behaviour similar to that of real prokaryotes