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1.
Sci Rep ; 10(1): 17013, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046755

RESUMO

Although doxorubicin (Dox) is an effective antitumor antibiotic in the anthracycline class, it often induces the undesirable side effect of cardiomyopathy leading to congestive heart failure, which limits its clinical use. The primary goal of this study is to evaluate a reliable translational method for Dox-induced cardiotoxicity (CTX) screening, aiming to identify a high-risk population and to discover new strategies to predict and investigate this phenomenon. Early identification of the presence of iron deposits and genetic and environmental triggers that predispose individuals to increased risk of Dox-induced CTX (e.g., overexpression of Toll-like receptor 4 (TLR4)) will enable the early implementation of countermeasure therapy, which will improve the patient's chance of survival. Our cohort consisted of 25 consecutive patients with pathologically confirmed cancer undergoing Dox chemotherapy and 12 control patients. The following parameters were measured: serum TLR4 (baseline), serum transferrin (baseline and 6-week follow-up) and iron deposition (baseline and 6-week follow-up). The average number of gene expression units was 0.121 for TLR4 (range 0.051-0.801). We subsequently correlated serum TLR4 levels in our cohort with myocardial iron overload using the cardiac magnetic resonance (CMR) T2* technique, the ventricular function (% ejection fraction, %EF) and serum transferrin levels. There is a strong negative linear relationship between serum TLR4 and CMR T2* values (r = - 0.9106, ****P < 0.0001). There is also a linear correlation (either positive or negative) with EF and transferrin; no established relationship related to the sex of the patients was found. Patients with elevated serum TLR4 at baseline also exhibited an increase in serum transferrin levels and Dox-induced left ventricular dysfunction with a decreased EF (< 50%); this phenomenon was observed in 7 of 25 patients (28%) at the 6-week follow-up. There were no significant differences or correlations based on sex. We concluded that there is a direct relationship between Dox-induced CTX (indicated by elevated serum TLR4) and the times (ms) for T2* (decreases in which correspond to immediate and rapid iron overload).


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Doxorrubicina/efeitos adversos , Neoplasias Hematológicas/tratamento farmacológico , Sobrecarga de Ferro/induzido quimicamente , Receptor 4 Toll-Like/metabolismo , Adolescente , Adulto , Idoso , Antibióticos Antineoplásicos/uso terapêutico , Cardiomiopatias/metabolismo , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Doxorrubicina/uso terapêutico , Feminino , Neoplasias Hematológicas/metabolismo , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Medição de Risco , Receptor 4 Toll-Like/genética , Transferrina/metabolismo , Adulto Jovem
2.
Rom J Morphol Embryol ; 61(4): 1121-1128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34171061

RESUMO

Changes in the lining of the small intestine following chemotherapy have been extensively studied, although also occurs in the large intestine. The aim of this study was to assess the consequences of Epirubicin-based therapy on goblet cells (GCs) and mucus production on colonic mucosa, immediately and after short-time of chemotherapy administration to oncohematological patients, by clinical and histopathological analysis. We assessed the mucus production, composition, and distribution by Alcian Blue (pH 2.5)-Periodic Acid-Schiff (PAS) staining, alongside with the immunoexpression of mucin (MUC)2, MUC4 and inflammatory markers in a series of oncohematological patients, immediately and after short-time of Epirubicin-based chemotherapy cumulative therapy cessation. We showed that GCs number decrease slightly at 48 hours, while mucous secretion became mixed (with a few neutral) after three weeks. Overall, the secretion was increased immediately after the Epirubicin administration, due to the activation of inflammatory pathways, assessed by increased immunostaining of tumor necrosis factor-alpha (TNF-α) at 48 hours. The MUC2 and MUC4 showed a decreased immunoexpression at 48 hours after the Epirubicin administration compared to controls and partially restored three weeks after the cessation. Overall, it is highly plausible that all these key players revolve around the chemotherapy-induced mucositis in oncohematological patients and highlights the morphofunctional particularities of the GCs, which further modulates the clinical outcome of the patient.


Assuntos
Células Caliciformes , Mucinas , Colo , Epirubicina/efeitos adversos , Humanos , Mucosa Intestinal , Mucina-2
3.
Rom J Morphol Embryol ; 58(2): 681-683, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28730261

RESUMO

Stevens-Johnson syndrome (SJS) is a cutaneous mucosal disorder characterized by extended necrosis and detachment of the epidermis affecting <10% of the body surface, caused by drugs or infections. The authors report a case of a girl with Depakine resistant epilepsy, who develops a SJS in the third week of introducing lamotrigine. The girl also presents an acute diarrheal disease with double viral etiology - rotavirus and norovirus. The clinical image comprises polymorphic erythematous maculopapular exanthema with vesicular and bullous elements, with ulcerations and desquamations at the level of the eyelids, mouth, anogenital area and tegument denuding at the level of the abdomen and limbs. The SCORTEN score (SCORe of Toxic Epidermal Necrosis) for establishing the seriousness is 1. The evolution of the disease is slowly favorable under conservative treatment, which does not involve the use of corticotherapy or intravenous immunoglobulins. Although there is a low incidence of this syndrome in pediatrics, it may occur as complication of using some drugs - mostly anti-epileptics or antibiotics, corroborated or not with an infectious process.


Assuntos
Norovirus/patogenicidade , Infecções por Rotavirus/complicações , Síndrome de Stevens-Johnson/etiologia , Pré-Escolar , Feminino , Humanos , Síndrome de Stevens-Johnson/patologia
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