Navegando por Palavras-chave "Liver Regeneration"
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- ItemSomente MetadadadosAnálise das citocinas relacionadas à regeneração do fígado remanescente após técnicas de ressecção hepática em dois tempos com ligadura da veia porta: modelo experimental em suínos(Universidade Federal de São Paulo (UNIFESP), 2019-10-31) Silva, Luciana Cristina Da [UNIFESP]; Linhares, Marcelo Moura [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: For most patients with malignant liver tumors, hepatectomy is the only therapeutic modality capable of increasing long-term survival or even cure, but only 10-25% of these patients are resectable on presentation of the disease. Insufficient future liver remnant (FRL) is the leading cause of unresectability of these lesions and portal vein ligation (PVL) is traditionally used to increase the FRL. ALPPS is a new approach that combines hepatic bipartition with PVL, leading to more significant liver regeneration than PVL alone. In this experimental study, we aimed to analyze cytokines related to FRL growth. Methods: Seven pigs were submitted to the first stage of ALPPS and in 7 other animals, only portal vein ligation (PVL) was performed. We compared the ALPPS group with the PVL group for the following variables: serum cytokine levels, FRL growth parameters, mitosis and Ki-67 positive cell count in the FRL. Also, regardless of ALPPS or LVP group, we divided the animals between low and high liver regeneration according to median values of FRL weight, number of mitoses per 10 high power fields and remnant liver Ki-67 in the FRL. Results: We identified higher serum levels of IL-6, TNF- and IL-1 in the group with higher FRL weight gain. In animals with higher cell proliferation (mitoses and Ki-67) we found lower levels of IL-12. There was no difference in FRL growth between the ALPPS and LVP groups. Conclusion: In this study we were able to identify cytokines IL-6, TNF-, IL-1 and IL-12 as inflammatory factors related to liver regeneration (FRL weight and cell proliferation), although we did not observe any difference in FRL regeneration between the ALPPS and LVP groups.
- ItemAcesso aberto (Open Access)Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?](Acta Cirurgica Brasileira, 2017) Soares Alves, Ana Karina [UNIFESP]; Lanzoni, Valeria [UNIFESP]; Fuziy, Rogerio Aoki [UNIFESP]; Monteiro Moura Franco, Rita Maria Aparecida [UNIFESP]; Maeda, Carlos Toshinori [UNIFESP]; Lopes Filho, Gaspar de Jesus [UNIFESP]; Linhares, Marcelo Moura [UNIFESP]Purpose: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. Methods: Forty rats were subjected to 70% hepatectomy and then similar to 10(6) mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. Results: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05). Conclusions: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.
- ItemSomente MetadadadosEfeito Do Condroitim Sulfato Na Fibrogênese Hepática Induzida Por Ligadura Do Ducto Biliar Em Ratos(Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Guedes, Pedro Luiz Rodrigues [UNIFESP]; Nagaoka, Márcia Regina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background and Aims: One of the many causes of hepatic fibrosis is cholestasis, which causes cell death and triggers cytokines and chemokines release, leading to leukocyte infiltration and extracellular matrix deposition. The current treatment of hepatic fibrosis is based on withdrawal of the causing agent, so the investigation of new and effective strategies for the treatment of liver fibrosis is very important. Many studies highlight the action of chondroitin sulfate (CS) in different cell types, leading to the reduction of cytokines expression. The aim of this work was to analyze effects of CS on experimental model of extra-hepatic cholestasis induced by common bile duct ligation (BDL). Methods: Wistar rats (6-8 weeks) were submitted to BDL, treated with CS (120 mg/kg body) or vehicle for 1, 2, 7, 14, 21 or 28 days intraperitoneally, and then euthanized; sham animals were used as control. We analyzed serum alanine and aspartate aminotransferases (ALT and AST, respectively) activities and performed histomorphometric analysis on Picrosirius-stained liver specimens using the Axiovision software. To analyze cell death and inflammation, caspase-3 and cathepsin B activities on liver homogenates were measured using fluorometric substrates Ac-DEVD-AMC and Abz-GIVRAK(Dnp)-OH, respectively. Apoptosis was also evaluated by TUNEL assay and liver regeneration by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using monoclonal primary anti-PCNA antibody. Statistical analysis of standardized values was performed by one-way ANOVA with Tukey’s post-hoc. Results are expressed by mean±SEM. Results: BDL rats presented ALT and AST serum activities 2-3 times greater than sham. BDL led to progressive fibrotic septa development, which was confirmed by measuring collagen content (% field) after 7 (11±1, n = 7), 14 (14±1, n = 10), 21 (23±1, n = 4) and 28 (34±3, n = 7) days of induction, while sham group preserved normal liver architecture. CS treatment reduced collagen content on BDL group after 21 days (14±1, n = 6) and significantly (p<0.0001) after 28 days (16±2, n = 6). There were no significant changes on cathepsin B activities of all studied groups. We verified increasing caspase-3 activity (fold sham) on BDL 2d (1.4±0.1, n = 5), 7d (2.2±0.6, n = 7) and 14d (3.3 ± 0.5, n = 10; ANOVA, p < 0.001) when compared to the respective sham groups. Interestingly, CS reduced significantly (p=0.043) the caspase-3 activity after 14 days of treatment (1,7 ±0.7, n = 9) when compared to BDL 14d group. BDL animals had a higher number of apoptotic cells per field (% of total) at 14d (0.58±0.04) than those at 7 (0.25±0.02), 21 (0.33±0.02)and 28 days groups (0.29±0.01). Treatment with CS reduced significantly (p = 0.030) the number of apoptotic cells in the 14d group (0.43±0.04). In addition, BDL led to an increase in the relative amount (% of total) of PCNA-labeled epithelial biliary cells and hepatocytes. Treatment with CS led increased amounts of marked hepatocytes at 14d (2.9±0.1 – ANOVA; p = 0.003) and 21d (3.5±0.2 - ANOVA; p < 0.001) when compared to non-treated groups (2.1±0.1 and 2.2±0.2 respectively). Conclusions: This work shows that CS may reduce first signs of apoptosis, slow down development of liver fibrosis and therefore cirrhosis, besides promoting liver regeneration on experimental model of common bile duct ligation.