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1.
Hematology ; 29(1): 2331940, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38526293

RESUMO

BACKGROUND: Endari (L-glutamine) is a conditional amino acid that reduces the frequency of vaso-occlusive crisis (VOC) in sickle cell disease (SCD). AIM: To investigate whether Endari could ameliorate intestinal barrier function and improve survival outcomes in SCD. METHODS: We treated female Townes SCD mice with Endari and evaluated their intestinal barrier functions by measuring the recovery of orally administered fluorescein isothiocyanate (FITC)-conjugated dextran 4 kDa in serum, and serum intestinal fatty acid binding proteins (iFABP) and lipopolysaccharide (LPS) concentrations by ELISA. We also explored the impact the Endari has on the survival of the SCD mice that underwent repeated experimentally-induced VOC. RESULTS: Compared to SCD mice treated with water only, Endari-treated mice showed improved intestinal barrier functions, with decrease in the barrier permeability and reduction in the translocation of lipopolysaccharides from the intestinal lumen into the circulation. These changes occurred after only 4 weeks of Endari treatment. Improved intestinal barrier function was also associated with prolonged survival in Endari-treated SCD mice after repeated experimentally-induced VOC. CONCLUSION: Our findings provide the evidence supporting the beneficial effects of Enadri in improving intestinal barrier function and associated survival outcomes in SCD.


Assuntos
Anemia Falciforme , Dextranos , Fluoresceína-5-Isotiocianato/análogos & derivados , Hemoglobinopatias , Compostos Orgânicos Voláteis , Feminino , Humanos , Animais , Camundongos , Glutamina , Função da Barreira Intestinal , Anemia Falciforme/tratamento farmacológico
2.
Am J Hematol ; 92(10): 1079-1084, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28612456

RESUMO

The National Comprehensive Cancer Network (NCCN) recommends that a repeat bone marrow evaluation is carried out seven to ten days following completion of induction therapy so that if a patient's day 14 bone marrow shows residual blast cell counts of >10%, the patient would proceed early to a second cycle of induction therapy. Although blast cell counts of <5% on day 14 bone marrow is sensitive in predicting remission on day 28, various studies have found that day 14 bone marrow is highly nonspecific because a large proportion of patients with blast cell counts of >5% on day 14 bone marrow would still attain a complete remission of the disease without any further chemotherapy. Clinical decision based on day 14 bone marrow will result in some of these patients being given a second induction therapy unnecessarily. A second cycle of chemotherapy is associated with not only higher risk for treatment-related mortality but also increased use of hospital resources such as increased intravenous antimicrobials use, longer hospital stay, and higher demand for blood products. In this article, we examined the utility, discussed the shortfalls, and re-appraised the values of day 14 bone marrow in the management of patients with AML. On the basis of our review, we suggest that the practice of day 14 bone marrow examination should be re-evaluated and should probably only be carried out in the setting of clinical trials with clear questions to address its role in predicting outcome of the therapeutic intervention.


Assuntos
Medula Óssea/patologia , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/terapia , Exame de Medula Óssea/métodos , Tomada de Decisão Clínica , Humanos , Leucemia Mieloide Aguda/patologia , Neoplasia Residual/patologia , Valor Preditivo dos Testes , Indução de Remissão , Retratamento , Fatores de Tempo
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