Functionalization of single and multi-walled carbon nanotubes with polypropylene glycol decorated pyrrole for the development of doxorubicin nano-conveyors for cancer drug delivery

A recently reported functionalization of single and multi-walled carbon nanotubes, based on a cycloaddition reaction between carbon nanotubes and a pyrrole derived compound, was exploited for the formation of a doxorubicin (DOX) stacked drug delivery system. The obtained supramolecular nano-conveyors were characterized by wide-angle X-ray diffraction (WAXD), thermogravimetric analysis (TGA), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. The supramolecular interactions were studied by molecular dynamics simulations and by monitoring the emission and the absorption spectra of DOX. Biological studies revealed that two of the synthesized nano-vectors are effectively able to get the drug into the studied cell lines and also to enhance the cell mortality of DOX at a much lower effective dose. This work reports the facile functionalization of carbon nanotubes exploiting the “pyrrole methodology” for the development of novel technological carbon-based drug delivery systems

Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors

Current clinical research suggests that fatty acid-binding protein 4 inhibitors (FABP4is), which are of biological and therapeutic interest, may show potential in treating cancer and other illnesses. We sought to uncover new structures through the optimization of the previously reported 4-amino and 4-ureido pyridazinone-based series of FABP4is as part of a larger research effort to create more potent FABP4 inhibitors. This led to the identification of 14e as the most potent analog with IC₅₀ = 1.57 μM, which is lower than the IC₅₀ of the positive control. Advanced modeling investigations and in silico absorption, distribution, metabolism, and excretion - toxicity calculations suggested that 14e represents a potential candidate for in vivo studies such as FABP4i

Exploring the Association Between Suicidal Thoughts, Self-Injury, and GLP-1 Receptor Agonists in Weight Loss Treatments: Insights from Pharmacovigilance Measures and Unmasking Analysis

© 2024 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA). Aim: The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators. Methods: Descriptive and pharmacovigilance disproportionality analyses was performed. Results: A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 ‘serious’ cases related to selected ADRs were registered during 2005–2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide). Discussion: Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations. Conclusions: With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.Peer reviewe

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

O livro "Direitos das mulheres e injustiça dos homens" de Nísia Floresta: literatura, mulheres e o Brasil do século XIX

O livro Direitos das mulheres e injustiça dos homens foi publicado por Dionísia Gonçalves Pinto (1810-1885), mais conhecida como Nísia Floresta, em 1832. Tal obra foi considerada uma tradução livre de A Vindication of the rights of woman de Mary Wollstonecraft (1759-1797), autora inglesa que se tornou o principal nome em defesa dos direitos das mulheres no século XIX. No entanto, tratava-se da tradução de Woman not inferior to man de Mary Wortley Montagu (1689-1762). O artigo apresentado contextualiza o livro de Wollstonecraft no período, enfoca a trajetória da autora brasileira e a influência do Positivismo na sua obra, principalmente no que tange ao papel social das mulheres

Aristotele nella societ\ue0 contemporanea

L\u2019Aristotele nel Novecento di Enrico Berti apparve per i tipi di Laterza nel 1992. Sono passati quattordici anni, dei quali tutto si pu\uf2 dire tranne che l\u2019interesse per Aristotele sia diminuito. Da una parte, grazie agli studi di Alfredo Ferrarin e Theodore Kisiel, gli status quaestionis relativi all\u2019influenza di Aristotele su Hegel e Heidegger hanno assunto proporzioni tali da sconsigliare di darne trattazioni brevi e frammentarie e tenerli invece in serbo per futuri numeri monografici ; dall\u2019altra, la trasformazione nel 1997 del Centro per la Storia della Tradizione Aristotelica nel Veneto dell\u2019Universit\ue0 di Padova nel Centro Interuniversitario per la Storia della Tradizione Aristotelica, diretto attualmente dallo stesso Berti (e al quale hanno nel frattempo aderito l\u2019Universit\ue9 de Bourgogne-Dijon, l\u2019Universit\ue0 della Calabria, l\u2019Universit\ue0 di Lecce, l\u2019Universit\ue0 di Palermo e l\u2019Universit\ue0 di Verona), non solo ha dato luogo a ricerche specialistiche di altissimo livello, ma ha anche contribuito a diffondere la percezione che se \ue8 vero che non \ue8 mai stato facile avere a che fare con Aristotele, \ue8 anche vero che il premio per chi vi si cimenta \ue8 ragguardevole \u2013 come del resto \ue8 stato provato dal successo incontrato dai volumi sull\u2019impatto di Aristotele e dell\u2019aristotelismo nella storia della filosofia curati da Sir Anthony Kenny, R. W. Sharples, Gregorio Piaia e chi scrive . Con molta modestia e senza pensare alla completezza, l\u2019obiettivo di questo numero monografico \ue8 riprendere le fila di diverse controversie aristoteliche l\ue0 dove erano state lasciate nell\u2019Aristotele nel Novecento. Ogni contributo illumina il ruolo svolto dalla filosofia di Aristotele nella societ\ue0 a cavallo del millennio rispetto a diversi nuclei tematici. Enrico Berti affronta la genetica riprendendo e concludendo gli argomenti che lo videro protagonista nei mesi che precedettero il referendum italiano sulla fecondazione assistita del 2004. Franco Buzzi ricostruisce l\u2019Aristotele dei teologi novecenteschi; Tommaso Tuppini indaga l\u2019Aristotele di pertinenza dell\u2019ecologia contemporanea; e Marco Sgarbi presenta la proposta di John McDowell sul nesso tra natura e conoscenza. Inoltre Serena Floresta rintraccia Aristotele in J\ufcrgen Habermas; Antonio Da Re considera e valuta le pi\uf9 recenti discussioni relative all\u2019Etica e Gabriele De Anna quelle relative alla Politica. Chiude il volume il grande filosofo statunitense Jude P. Dougherty con un contributo sulla presenza di Aristotele nella filosofia nordamericana, che colma una grave lacuna nelle storie della filosofia di quella parte del mondo

Temporal trends in characteristics, treatment, and outcomes of heart failure in octogenarians over two decades

Introduction and objectives: Octogenarians represent the most rapidly expanding population segment in Europe. The prevalence of heart failure (HF) in this group exceeds 10%. We assessed changes in clinical characteristics, therapy, and 1-year outcomes over 2 decades in chronic HF outpatients aged ≥ 80 years enrolled in a nationwide cardiology registry. Methods: We included 2520 octogenarians with baseline echocardiographic ejection fraction measurements and available 1-year follow-up, who were recruited at 138 HF outpatient clinics (21% of national hospitals with cardiology units), across 3 enrolment periods (1999-2005, 2006-2011, 2012-2018). Results: At recruitment, over the 3 study periods, there was an increase in age, body mass index, ejection fraction, the prevalence of obesity, diabetes, dyslipidemia, pre-existing hypertension, and atrial fibrillation history. The proportion of patients with preserved ejection fraction rose from 19.4% to 32.7% (P for trend < .0001). Markers of advanced disease became less prevalent. Prescription of beta-blockers and mineralocorticoid receptor antagonists increased over time. During the 1-year follow-up, 308 patients died (12.2%) and 360 (14.3%) were admitted for cardiovascular causes; overall, 591 (23.5%) met the combined primary endpoint of all-cause mortality or cardiovascular hospitalization. On adjusted multivariable analysis, enrolment in 2006 to 2011 (HR, 0.70; 95%CI, 0.55-0.90; P = .004) and 2012 to 2018 (HR, 0.61; 95%CI, 0.47-0.79; P = .0002) carried a lower risk of the primary outcome than recruitment in 1999 to 2005. Conclusions: Among octogenarians, over 2 decades, risk factor prevalence increased, management strategies improved, and survival remained stable, but the proportion hospitalized for cardiovascular causes declined. Despite increasing clinical complexity, in cardiology settings the burden of hospitalizations in the oldest old with chronic HF is declining