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2.
Chin J Traumatol ; 27(2): 114-120, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37311687

RESUMO

PURPOSE: Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. METHODS: The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group (n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group (n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. RESULTS: In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) µm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) µm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels. CONCLUSIONS: NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Preservação de Órgãos , Animais , Cães , Temperatura , Preservação de Órgãos/métodos , Perfusão/métodos , Extremidade Superior , Membro Anterior , Aumento de Peso , Fígado
3.
Sci Rep ; 8(1): 3079, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449573

RESUMO

The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear. In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell survival. The B1 protein of the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1 grouper cells as early as 24 hours post-infection (hpi). Using an EYFP-B1 fusion construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1 cells at 48 hpi. The nuclear localization of B1 was mediated by two arginine-rich nuclear targeting domains (B domain: 46RRSRR51; C domain: 63RDKRPRR70) and domain C was more important than domain B in this process. B1 nuclear localization correlated with upregulation of p53 and p21(wef1/cip1); downregulation of Cyclin D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells. In conclusion, nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby regulating host cell survival.


Assuntos
Nodaviridae/enzimologia , Nodaviridae/genética , Nodaviridae/metabolismo , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Arginina/metabolismo , Ciclo Celular , Pontos de Checagem do Ciclo Celular/fisiologia , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/fisiologia , Sinais de Localização Nuclear/genética , Sinais de Localização Nuclear/metabolismo , Domínios Proteicos , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo
4.
Pharmacotherapy ; 30(1): 113, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20030482

RESUMO

The antimetabolite mercaptopurine is commonly used as part of treatment regimens for acute lymphoblastic leukemia and as treatment for inflammatory bowel diseases. Adverse effects associated with mercaptopurine include myelosuppression, hepatotoxicity, and hyperpigmentation. We describe a 36-year-old man with Philadelphia chromosome-negative pre-B-cell acute lymphoblastic leukemia who experienced a serious mercaptopurine-induced hypersensitivity reaction requiring prolonged hospitalization and extensive laboratory testing and imaging. He was treated with a multiagent chemotherapy regimen. Mercaptopurine 60 mg/m(2)/day orally was started as part of his third course of chemotherapy. On day 9 of mercaptopurine therapy, the patient developed persistent fevers, skaking chills, and rigors that persisted in the absence of documented infection, consistent with drug fever. All symptoms and signs resolved after discontinuation of mercaptopurine. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of fever and mercaptopurine therapy. Mercaptopurine-induced fever has been reported in patients with inflammatory bowel diseases, but this case report is the first, to our knowledge, in a patient with acute lymphoblastic leukemia. Health care professionals should be aware of the possible development of fever as a hypersensitivity reaction in patients with acute lymphoblastic leukemia treated with mercaptopurine.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/imunologia , Hipersensibilidade a Drogas/etiologia , Febre/induzido quimicamente , Mercaptopurina/efeitos adversos , Mercaptopurina/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Masculino , Mercaptopurina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações
5.
Virology ; 385(2): 444-54, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19136133

RESUMO

The functions of the Betanodavirus non-structural protein B1 is still unknown. We examined B1 expression patterns and investigated novel cell death regulatory functions for this viral protein following RGNNV infection in fish cells. The B1 gene (336 nt) was cloned from the redspotted grouper nervous necrosis virus (RGNNV) genome. B1 mRNA was rapidly expressed in the fish cells from viral RNA3 at 12 h post-infection (p.i.). At the protein level, expression was low at 12 h p.i., and then increased rapidly between 24 h and 72 h p.i. In RGNNV-infected, B1-containing fish cells, over expression of RGNNV B1 reduced Annexin-V positive cells by 50% and 65% at 48 h and 72 h p.i., respectively, and decreased loss of mitochondrial membrane potential (MMP) by 20% and 70% at 48 h and 72 h p.i., respectively. Finally, B1 knockdown during RGNNV infection using anti-sense RNA increased necrotic cell death and reduced cell viability during the early replication cycle (24 h p.i.). Our results suggest that B1 is an early expression protein that has an anti-necrotic cell death function which reduces the MMP loss and enhances viral host cell viability. This finding provides new insights into RNA viral pathogenesis and disease control.


Assuntos
Peixes/virologia , Nodaviridae/genética , Nodaviridae/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Morte Celular/fisiologia , Linhagem Celular , Clonagem Molecular , Regulação Viral da Expressão Gênica , Técnicas de Silenciamento de Genes , Membranas Mitocondriais/virologia , Dados de Sequência Molecular , RNA Viral/genética , RNA Viral/metabolismo , Alinhamento de Sequência , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética
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