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Reações adversas a medicamento sem pacientes hospitalizados por insuficiência hepática crônica moderada ou grave em hospitais do Nordeste do Brasil

Thu, 01 Jan 2026 00:00:00 GMT

Título: Reações adversas a medicamento sem pacientes hospitalizados por insuficiência hepática crônica moderada ou grave em hospitais do Nordeste do Brasil Autor(es): Araújo, Breno Queiroz de Abstract: Chronic liver failure (CLF) is characterized by progressive and irreversible loss of liver function, which may lead to alterations in the pharmacokinetics of various medications and increased susceptibility to adverse drug reactions (ADRs). In this context, the clinical pharmacist plays a fundamental role in the prevention, identification, and management of these reactions. This study aimed to characterize the incidence, determinants, and clinical relevance of ADRs in patients hospitalized with moderate to severe CLF in hospitals in the Northeast region of Brazil. This is an observational, analytical, multicenter prospective cohort study that included patients with moderate to severe CLF (Child-Pugh B or C) hospitalized in seven hospitals in Northeast Brazil between September 2023 and January 2026. Daily collection of clinical, laboratory, and pharmacotherapeutic data was performed, with active surveillance of ADRs through medical record review, trigger tools, and reports from the healthcare team and patients. ADRs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA®) and classified regarding causality, severity, and preventability using validated tools. Data analysis was performed using Stata 15®, adopting a significance level of p < 0.05. A total of 252 patients were included, with a predominance of males (59.1%) and a mean age of 59.2 years. Overall, 38.9% of patients experienced at least one ADR, totaling 207 events. The most frequent ADRs involved gastrointestinal, nervous system, and metabolic disorders, with furosemide, lactulose, and carvedilol identified as the main suspected drugs. Most ADRs were classified as probable or possible, of mild severity, and largely preventable. ADRs were associated with longer follow-up time, previous upper gastrointestinal bleeding, and laboratory abnormalities suggestive of hepatic and renal dysfunction, such as elevated urea, bilirubin, and aspartate aminotransferase (AST), as well as hyponatremia. ADRs were also associated with relevant clinical outcomes, including hepatorenal syndrome, prophylactic variceal ligation, acute-on-chronic liver failure, jaundice, and hepatic coma. In conclusion, ADRs are frequent in patients with CLF, many of which are preventable, and are associated with worse clinical outcomes, highlighting the need for rigorous pharmacotherapeutic monitoring and strategies to ensure safe medication use in this population. Tipo: Dissertação

Avaliação da atividade de peptídeos derivados do veneno de Crotalus durissus terrificus sobre a criopreservação espermática

Thu, 01 Jan 2026 00:00:00 GMT

Título: Avaliação da atividade de peptídeos derivados do veneno de Crotalus durissus terrificus sobre a criopreservação espermática Autor(es): Moura, Gabriel Acácio de Tipo: Tese

Investigação da relação do polimorfismo de nucleotídeo único (rs187238) no gene da interleucina-18 e do tempo de isquemia fria com a função do enxerto em receptores de transplante renal de um Hospital Universitário de Fortaleza

Thu, 01 Jan 2026 00:00:00 GMT

Título: Investigação da relação do polimorfismo de nucleotídeo único (rs187238) no gene da interleucina-18 e do tempo de isquemia fria com a função do enxerto em receptores de transplante renal de um Hospital Universitário de Fortaleza Autor(es): Duque, Bruna Ribeiro Abstract: Renal dysfunction is a common complication among recipients of organs from deceased donors and can be caused by ischemia-reperfusion injury, which affects the therapeutic success of the transplant. Cold ischemia time (CIT) refers to the period of organ transport, from its removal from the donor to its implantation in the recipient. Prolonged periods of CIT can influence renal graft survival, causing irreversible renal injury. In the search for early biomarkers of renal function, urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) may be potential predictors of graft dysfunction. IL-18 is a proinflammatory cytokine that may be involved in modulating the immune response related to acute kidney injury. The single nucleotide polymorphism rs187238 (-137G/C), located in the gene for this interleukin, is known to cause an increase in the expression of this cytokine, which may influence the individual's inflammatory profile. The present study sought to investigate the influence of the rs187238 polymorphism and CIT on graft function in kidney transplant recipients. The work is structured in three articles. The first is a narrative review on the influence of CIT on delayed graft renal function. The other articles are cross-sectional studies including renal allograft recipients from a university hospital in Fortaleza between 2023 and 2025. These studies evaluated the influence of CIT, urinary IL-18 levels, and rs187238 polymorphism genotypes on graft renal function one month after transplantation. It was observed that prolonged periods of cold ischemia are related to longer hospital stays and graft renal dysfunction, reflected in higher serum creatinine levels, lower estimated glomerular filtration rate (eGFR), and higher urinary NGAL levels. Urinary IL-18 levels and rs187238 polymorphism genotypes had no influence on clinical parameters of renal function one month post-transplant. It is concluded that urinary IL-18 is not characterized as a biomarker of renal injury in this period, and its rs187238 polymorphism did not impact the markers of renal function of the allograft. In addition, the findings demonstrate that CIT can determine the patient's prognosis and the therapeutic success of the transplant. Tipo: Dissertação

Avaliação da atividade in vitro dos derivados sintéticos de N-ciclohexil 3-(3-metilfenil)1,2,4-oxadiazol-5-amina sobre a cepa y de Trypanosoma cruzi e um estudo de toxicidade in vivo

Thu, 01 Jan 2026 00:00:00 GMT

Título: Avaliação da atividade in vitro dos derivados sintéticos de N-ciclohexil 3-(3-metilfenil)1,2,4-oxadiazol-5-amina sobre a cepa y de Trypanosoma cruzi e um estudo de toxicidade in vivo Autor(es): Rocha, Yasmim Mendes Abstract: Chagas disease remains a significant public health problem in Latin America, primarily treated with Nifurtimox and Benznidazole. Despite initial proactive strategies, these medications have limitations, such as low efficacy in the chronic phase and adverse effects. In this context, heterocyclic compounds, such as 1,2,4-oxadiazole derivatives, have been investigated as potential therapeutic alternatives. This study aimed to evaluate the trypanocidal activity and toxicity of molecules 2a, 2f, and 2i against the Trypanosoma cruzi strain using in vitro, in silico, and in vivo assays. The results showed a concentration-dependent effect on epimastigote forms, with IC50 values of 31.4 µM, 44.4 µM, and 7.0 µM for 2a, 2f, and 2i, respectively. In trypomastigotes, LC50 values of 14.2 µM, 2.4 µM, and 2.6 µM were observed for these same molecules, in addition to a significant reduction in the amastigote load in infected cells. The selectivity index was 15, 5.8, 9.8, and 4.7 for molecules 2a, 2f, 2i, and benznidazole, respectively. Flow cytometry analyses indicated compromised cell integrity, induction of oxidative stress, and mitochondrial dysfunction, altering different targets of action of the molecules under study. Using free radical neutralization assays in solution, through antioxidant activity and acetylcholinesterase inhibition, the molecules under study showed a high capacity for scavenging free radicals. These findings suggest that such compounds may interfere with the redox balance of the parasite, contributing to oxidative stress and, consequently, to the observed antiparasitic effects. Subsequently, scanning electron microscopy revealed membrane alterations, cell rounding, or flagellar absence. Among the compositions evaluated, molecule 2a stood out for presenting a better balance between efficacy and selectivity in vitro, in addition to interactions developed with the cruzipain enzyme in in silico analyses. In in vivo assays with zebrafish, molecule 2a showed dose-dependent embryonic toxicity (LC50~15 µM); similar to bzn at higher concentrations, decreasing a specific cytotoxic potential. Taken together, these findings reinforce the potential of 1,2,4-oxadiazole derivatives as promising candidates for the development of new therapeutic strategies against Chagas disease, highlighting molecule 2a as a priority target for future studies. Tipo: Tese