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1.
Acta Cir Bras ; 34(11): e201901103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939502

RESUMO

PURPOSE: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. METHODS: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. RESULTS: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. CONCLUSION: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.


Assuntos
Artéria Hepática/cirurgia , Regeneração Hepática/fisiologia , Fígado/diagnóstico por imagem , Veia Porta/cirurgia , Animais , Hepatomegalia/diagnóstico por imagem , Hepatomegalia/fisiopatologia , Imagem Tridimensional/métodos , Imuno-Histoquímica , Ligadura , Fígado/irrigação sanguínea , Fígado/patologia , Masculino , Tamanho do Órgão/fisiologia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
J Surg Res ; 246: 568-583, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31653415

RESUMO

BACKGROUND: Coagulation disturbances in several liver diseases lead to thrombin generation, which triggers intracellular injury via activation of protease-activated receptor-1 (PAR-1). Little is known about the thrombin/PAR-1 pathway in hepatic ischemia-reperfusion injury (IRI). The present study aimed to clarify whether a newly selective PAR-1 antagonist, vorapaxar, can attenuate liver damage caused by hepatic IRI, with a focus on apoptosis and the survival-signaling pathway. METHODS: A 60-min hepatic partial-warm IRI model was used to evaluate PAR-1 expression in vivo. Subsequently, IRI mice were treated with or without vorapaxar (with vehicle). In addition, hepatic sinusoidal endothelial cells (SECs) pretreated with or without vorapaxar (with vehicle) were incubated during hypoxia-reoxygenation in vitro. RESULTS: In naïve livers, PAR-1 was confirmed by immunohistochemistry and immunofluorescence analysis to be located on hepatic SECs, and IRI strongly enhanced PAR-1 expression. In IRI mice models, vorapaxar treatment significantly decreased serum transaminase levels, improved liver histological damage, reduced the number of apoptotic cells as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (median: 135 versus 25, P = 0.004), and induced extracellular signal-regulated kinase 1/2 (ERK 1/2) cell survival signaling (phospho-ERK/total ERK 1/2: 0.96 versus 5.34, P = 0.004). Pretreatment of SECs with vorapaxar significantly attenuated apoptosis and induced phosphorylation of ERK 1/2 in vitro (phospho-ERK/total ERK 1/2: 0.66 versus 3.04, P = 0.009). These changes were abolished by the addition of PD98059, the ERK 1/2 pathway inhibitor, before treatment with vorapaxar. CONCLUSIONS: The results of the present study revealed that hepatic IRI induces significant enhancement of PAR-1 expression on SECs, which may be associated with suppression of survival signaling pathways such as ERK 1/2, resulting in severe apoptosis-induced hepatic damage. Thus, the selective PAR-1 antagonist attenuates hepatic IRI through an antiapoptotic effect by the activation of survival-signaling pathways.


Assuntos
Apoptose/efeitos dos fármacos , Lactonas/administração & dosagem , Fígado/irrigação sanguínea , Piridinas/administração & dosagem , Receptor PAR-1/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Receptor PAR-1/metabolismo , Traumatismo por Reperfusão/etiologia , Trombina/metabolismo
4.
J Trauma Acute Care Surg ; 88(2): 305-309, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31804421

RESUMO

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable resuscitation approach for a subdiaphragmatic injury that can regulate arterial blood flow. On the other hand, the evaluation of venous or portal venous blood flow during REBOA remains insufficient because invasive cannulation or exposure of the vessel may affect the blood flow, and Doppler echography is highly operator-dependent. However, phase contrast magnetic resonance imaging has enabled accurate evaluation and noninvasive measurement. This study aimed to investigate the change of venous and portal venous blood flow during REBOA in a porcine model. METHODS: Seven pigs were anesthetized, and a REBOA catheter was placed. The blood flows of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV), and superior vena cava (SVC) were measured using phase contrast magnetic resonance imaging, in both the balloon deflated (no-REBOA) and fully balloon inflated (REBOA) states. Mean arterial pressure (MAP), central venous pressure, cardiac index, and systemic vascular resistance index were measured. RESULTS: The blood flows of the suprahepatic, infrahepatic, and distal IVC, HV, and PV in the no-REBOA state were 1.40 ± 0.36 L·min, 0.94 ± 0.16 L·min, 0.50 ± 0.19 L·min, 0.060 ± 0.018 L·min, and 0.32 ± 0.091 L·min, respectively. The blood flow of each section in the REBOA condition was significantly decreased at 0.41 ± 0.078 (33% of baseline), 0.15 ± 0.13 (15%), 0.043 ± 0.034 (9%), 0.029 ± 0.017 (37%), and 0.070 ± 0.034 L·min (21%), respectively. The blood flow of the SVC increased significantly in the REBOA condition (1.4 ± 0.63 L·min vs. 0.53 ± 0.14 L·min [257%]). Mean arterial pressure, central venous pressure, cardiac index, and systemic vascular resistance index were significantly increased after REBOA inflation. CONCLUSION: Resuscitative endovascular balloon occlusion of the aorta decreased blood flows of the IVC, HV, and PV and increased blood flow of the SVC. This result could be explained by the collateral flow from the lower body to the SVC. A better understanding of the effect of REBOA on the venous and portal venous systems may help control liver injury.


Assuntos
Oclusão com Balão/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Sistema Porta/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Ressuscitação/efeitos adversos , Animais , Aorta/cirurgia , Oclusão com Balão/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/lesões , Imagem por Ressonância Magnética , Masculino , Modelos Animais , Sistema Porta/diagnóstico por imagem , Ressuscitação/métodos , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia , Suínos , Porco Miniatura
5.
J Surg Res ; 245: 410-419, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437648

RESUMO

BACKGROUND: The present study examined the impact of oxygenated machine perfusion on preservation of liver grafts donated after cardiac death by measuring sinusoidal endothelial injury and microcirculatory disturbances. MATERIALS AND METHODS: Fifteen porcine livers were retrieved 60 min after warm ischemia and allocated into three groups as follows: (1) CS group: static cold storage, (2) HMP group: oxygenated hypothermic perfusion preservation, (3) SNMP group: oxygenated subnormothermic perfusion preservation. The liver grafts donated after cardiac death were preserved for 4 h in different treatment conditions mentioned previously, then subject to ex vivo reperfusion for 2 h using diluted allogeneic blood. The hemodynamic parameters, liver function tests, tissue adenosine triphosphate (ATP) levels, and immunohistochemical findings were investigated. RESULTS: The number of sinusoidal epithelial cells and trabecular structures were maintained after 4 h of preservation in the CS, HMP, and SNMP group. Liver tissue ATP levels after 4 h of preservation in the HMP and SNMP groups were significantly higher compared with that in the CS group. The sinusoidal epithelial cells were significantly exfoliated to a more severe extent in the CS group than in the HMP and SNMP groups. Intrasinusoidal platelet aggregation occurred more frequently in the CS group than in the HMP and SNMP groups. CONCLUSIONS: The results indicated that oxygenated machine perfusion preservation was important to prevent the depletion of tissue ATP and maintain sinusoidal homeostasis regardless of the perfusate temperature. Our findings suggest oxygenated machine perfusion preservation as an effective alternative to static cold storage.


Assuntos
Transplante de Fígado , Fígado/irrigação sanguínea , Microcirculação , Preservação de Órgãos , Perfusão/métodos , Animais , Endotélio Vascular/patologia , Fígado/metabolismo , Fígado/patologia , Consumo de Oxigênio , Suínos
6.
Acta Cir Bras ; 34(10): e201901003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851211

RESUMO

PURPOSE: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. METHODS: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. RESULTS: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. CONCLUSIONS: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.


Assuntos
Conexina 43/deficiência , Modelos Animais de Doenças , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/metabolismo , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , Conexina 43/análise , Técnicas de Genotipagem , Fígado/patologia , Camundongos Knockout , Necrose , Reação em Cadeia da Polimerase , Valores de Referência , Traumatismo por Reperfusão/patologia , Fatores de Tempo , gama-Glutamiltransferase/análise
7.
Kathmandu Univ Med J (KUMJ) ; 17(65): 30-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734675

RESUMO

Background Extra hepatic portal vein obstruction (EHPVO) is a common cause of portal hypertension in the developing countries (up to 30% of all variceal bleeders) and is second to cirrhosis in the West (up to 5-10%). Our understanding of the disease is poor compared with other illnesses. Objective To undertake a retrospective study of the clinicoepidemiological profile of Extra hepatic portal vein obstruction in a tertiary care hospital in eastern Nepal. Method All consecutive adult patients whose features were consistent with the diagnosis of extra hepatic portal vein obstruction from June 2014 to June 2016 were retrospectively analyzed to explore the various clinico-epidemiological parameters. Result A total of 58 patients were enrolled in the study with a median age of 24 years (20.5- 40). Portal vein thrombosis was the most common cause of extrahepatic portal vein obstruction. Hematemesis followed by melena were the most common presenting symptoms. All patients had splenomegaly on examination. None of the patients had clinical, biochemical or radiological evidence of chronic liver disease. Conclusion The diagnosis of extra hepatic portal venous obstruction and differentiation from cirrhosis can be easily made by characteristic clinical features, normal liver function tests and doppler ultrasound. Portal vein thrombosis (PVT) is the predominant cause of extra hepatic portal vein obstruction in Nepali patients, as seen at this tertiary care hospital in Nepal.


Assuntos
Veia Porta/patologia , Doenças Vasculares/patologia , Trombose Venosa/etiologia , Adulto , Feminino , Humanos , Hipertensão Portal/etiologia , Fígado/irrigação sanguínea , Cirrose Hepática , Masculino , Melena , Nepal , Estudos Retrospectivos , Esplenomegalia , Centros de Atenção Terciária , Doenças Vasculares/complicações , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia , Adulto Jovem
8.
World J Gastroenterol ; 25(39): 6016-6024, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660037

RESUMO

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been adopted by liver surgeons in recent years. However, high morbidity and mortality rates have limited the promotion of this technique. Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant (FLR) similar to a complete split with better postoperative safety profiles. However, some others have suggested that ALPPS can induce more rapid and adequate FLR growth, but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS (p-ALPPS). AIM: To perform a systematic review and meta-analysis on ALPPS and p-ALPPS. METHODS: A systematic literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was performed for articles published until June 2019. Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included. Our main endpoints were the morbidity, mortality, and FLR hypertrophy rates. We performed a subgroup analysis to evaluate patients with and without liver cirrhosis. We assessed pooled data using a random-effects model. RESULTS: Four studies met the inclusion criteria. Four studies reported data on morbidity and mortality, and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis. In the non-cirrhotic group, p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPS-treated patients [odds ratio (OR) = 0.2; 95% confidence interval (CI): 0.07-0.57; P = 0.003 and OR = 0.16; 95%CI: 0.03-0.9; P = 0.04]. No significant difference in the FLR hypertrophy rate was observed between the two groups (P > 0.05). The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups. In contrast, ALPPS seemed to have a better outcome in the cirrhotic group. CONCLUSION: The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.


Assuntos
Hepatectomia/métodos , Hepatomegalia/epidemiologia , Regeneração Hepática , Veia Porta/cirurgia , Complicações Pós-Operatórias/epidemiologia , Hepatectomia/efeitos adversos , Hepatomegalia/etiologia , Humanos , Ligadura/efeitos adversos , Ligadura/métodos , Fígado/irrigação sanguínea , Fígado/fisiologia , Fígado/cirurgia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Análise de Sobrevida , Resultado do Tratamento
9.
Transplant Proc ; 51(9): 3111-3115, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611113

RESUMO

Extensive portosplenomesenteric thrombosis is regarded as a relative contraindication to liver transplantation because of the complexity of the surgical procedure. This report describes a case of living-donor liver transplantation (LDLT) for a patient with extensive portosplenomesenteric thrombosis, in whom portal flow was successfully restored by intraoperative transplenic portal vein and superior mesenteric vein stenting after surgical thrombectomy. The patient's liver function remained normal with a patent portal vein stent 6 months after LDLT, and Doppler ultrasonography demonstrated a normal wave form for portal flow. To the best of our knowledge, this is the world's first case of endovascular management of the portal vein via percutaneous transsplenic access during LDLT, demonstrating that transsplenic access can be an alternative approach without liver graft injury when the superior mesenteric vein branch and inferior mesenteric vein cannot be used as access routes.


Assuntos
Procedimentos Endovasculares/métodos , Transplante de Fígado/métodos , Veia Porta/cirurgia , Veia Esplênica/cirurgia , Trombose Venosa/cirurgia , Humanos , Fígado/irrigação sanguínea , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Trombose Venosa/complicações
10.
Curr Med Sci ; 39(5): 820-824, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612402

RESUMO

The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography. VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography. Conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) were performed 14 days after inoculation, and then the rabbits were sacrificed and pathologically examined. The success rate of inoculation was 100%. The average size of liver VX2 tumor was 1.7 cm×1.3 cm, CEUS of VX2 liver tumors showed the "rapid wash-in and wash-out" vascular pattern. There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A, k and A × k (P<0.05), which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma. Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor. And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.


Assuntos
Modelos Animais de Doenças , Neoplasias Hepáticas/patologia , Fígado/patologia , Neovascularização Patológica/diagnóstico por imagem , Animais , Velocidade do Fluxo Sanguíneo , Meios de Contraste/administração & dosagem , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Transplante de Neoplasias , Punções , Coelhos , Cirurgia Assistida por Computador/métodos , Carga Tumoral , Ultrassonografia/métodos
11.
Analyst ; 144(22): 6609-6616, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31616873

RESUMO

Maintaining the redox balance of biological systems is a key point to maintain a healthy physiological environment. Excessive iron ions (Fe3+) can cause apoptosis, tissue damage and death. Fortunately, ascorbic acid (AA) as a reducing agent has been evaluated for the reduction of Fe3+. Moreover, AA plays an important role in relieving hypoxia-induced oxidative stress. Therefore, the real-time imaging of the Fe3+ and AA fluctuations is important for understanding their biofunctions in cells and in vivo. In this work, we developed a fluorescent nanoprobe carbon dot-desferrioxamine B (CD-DB) by the conjugate connection of CDs and desferrioxamine B (a complexing agent for Fe3+) for the associated detection of Fe3+ and AA. CD-DB exhibited excellent sensitivity and selectivity for the detection of Fe3+ and AA. The nanoprobe CDs-DB@Fe obtained by the reaction of CD-DB and Fe3+ was suitable for tracing the dynamic changes of AA in cells and in vivo. Therefore, CDs-DB@Fe was used for monitoring the fluctuation of AA in hypoxic cell models, hypoxic zebrafish models and liver ischemia mice models. These results exhibited the decrease in AA under hypoxic conditions because AA was consumed to neutralize free radicals and relieve hypoxia-induced oxidative stress damage. The ideal biocompatibility and low toxicity make our nanoprobe a potential candidate for the research of the physiological effects of AA in vivo.


Assuntos
Ácido Ascórbico/análise , Corantes Fluorescentes/química , Hipóxia/metabolismo , Ferro/análise , Pontos Quânticos/química , Animais , Carbono/química , Hipóxia Celular , Desferroxamina/química , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Isquemia/metabolismo , Limite de Detecção , Fígado/irrigação sanguínea , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Estresse Oxidativo , Peixe-Zebra
12.
Acta Cir Bras ; 34(8): e201900805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618405

RESUMO

PURPOSE: To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury. METHODS: Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. RESULTS: The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. CONCLUSION: The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Isquemia/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , Peroxidase/análise , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
13.
BMC Cancer ; 19(1): 938, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601175

RESUMO

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/patologia , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Microesferas , Álcool de Polivinil/uso terapêutico , Amido/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Óleo Etiodado/administração & dosagem , Óleo Etiodado/efeitos adversos , Óleo Etiodado/uso terapêutico , Feminino , Artéria Hepática , Xenoenxertos , Fígado/irrigação sanguínea , Fígado/patologia , Masculino , Modelos Animais , Necrose/patologia , Neovascularização Patológica/tratamento farmacológico , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/efeitos adversos , Ratos , Amido/administração & dosagem , Amido/efeitos adversos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
14.
Acta Cir Bras ; 34(7): e201900707, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531528

RESUMO

PURPOSE: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. METHODS: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. RESULTS: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. CONCLUSION: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.


Assuntos
Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Fígado/fisiologia , Hepatopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
15.
Jpn J Radiol ; 37(11): 750-772, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522387

RESUMO

On the posterior aspect of the anterior abdominal wall, there are four kinds of "fine" ligaments. They are: the round ligament of the liver, median umbilical ligament (UL), a pair of medial ULs, and a pair of lateral ULs. Four of them (the round ligament, median UL, and paired medial ULs) meet at the umbilicus because they originate from the contents of the umbilical cord. The round ligament of the liver originates from the umbilical vein, the medial ULs from the umbilical arteries, and the median UL from the urachus. These structures help radiologists identify right-sided round ligament (RSRL) (a rare, but surgically important normal variant), as well as to differentiate groin hernias. The ligaments can be involved in inflammation; moreover, tumors can arise from them. Unique symptoms such as umbilical discharge and/or location of pathologies relating to their embryology are important in diagnosing their pathologies. In this article, we comprehensively review the anatomy, embryology, and pathology of the "fine" abdominal ligaments and highlight representative cases with emphasis on clinical significance.


Assuntos
Parede Abdominal , Ligamentos , Humanos , Fígado/irrigação sanguínea
16.
Transplant Proc ; 51(8): 2828-2832, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493917

RESUMO

OBJECTIVE: Hepatic ischemia and reperfusion (I/R) is a destructive event associated with high rates of liver failure after liver transplantation. Hesperidin significantly contributes to the antioxidant defense system and has been reported to act as a powerful agent against superoxide and hydroxyl radicals. Our objective was to investigate the protective effect of hesperidin against hepatic IR injury in a rat model. METHODS: We fed Sprague-Dawley rats either hesperidin (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats' common hepatic artery and portal vein for 30 minutes. The rats were divided into 3 groups: 1. the sham operated group; 2. the I/R group; and 3. the I/R-hesperidin group. RESULTS: Compared to the sham group, the I/R group had higher expression of serum aspartate aminotransferase and serum alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-hesperidin group had higher expression of catalase, superoxide dismutase, antioxidant and nitric oxide and lower expression of serum aspartate aminotransferase and serum alanine aminotransferase. CONCLUSIONS: Our findings suggest that hesperidin is a potential therapeutic agent for hepatic I/R injury.


Assuntos
Antioxidantes/uso terapêutico , Hesperidina/uso terapêutico , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Hesperidina/farmacologia , Hepatopatias/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo
17.
Transplant Proc ; 51(8): 2823-2827, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493918

RESUMO

OBJECTIVE: Hepatic ischemia reperfusion (I/R) injury is regarded as a serious concern in clinical practice. Citric acid reduces oxidative stress and inflammation during hypoxia and reoxygenation. Our objective was to investigate the protective effect of citric acid against hepatic I/R injury in rats. METHODS: We fed Sprague-Dawley rats either citric acid (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats' common hepatic artery and portal vein for 30 minutes. The rats were randomly divided into 3 major groups that were treated as follows: 1. the sham operated group; 2. the I/R group; and 3. the I/R-citric acid group. RESULTS: Compared to the sham group, the I/R group had higher expression of aspartate aminotransferase and alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-citric acid group had higher expression of catalase, superoxide dismutase, antioxidants, and nitric oxide, and lower expression of aspartate aminotransferase and alanine aminotransferase. CONCLUSIONS: These results suggest that citric acid therapy has significant therapeutic potential in ischemic liver injury.


Assuntos
Antioxidantes/uso terapêutico , Ácido Cítrico/uso terapêutico , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Ácido Cítrico/farmacologia , Glutationa Peroxidase/metabolismo , Hepatopatias/metabolismo , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo
18.
Biomed Pharmacother ; 118: 109031, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545219

RESUMO

BACKGROUND: This study was conducted to investigate the protective effect of Fms-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L)-dependent CD103+ dendritic cells (DCs) on hepatic ischemia-reperfusion injury (IRI). METHODS: A mouse model of hepatic IRI and cellular model following hypoxia-reperfusion (H/R) treatment were established. Peripheral blood and liver tissues were obtained and analyzed by flow cytometer in terms of percentage of CD103+DCs and regulatory T (Treg) cells. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined to assess liver function. Moreover, pro-inflammatory cytokines levels including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The histological morphology of liver tissues was examined with hematoxylin and eosin (HE) staining. The apoptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) assay. Treg-associated cytokines transforming growth factor (TGF)-ß and IL-10 expressions were measured using quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: CD103+ DCs were significantly decreased in peripheral blood and liver tissues of mouse model of hepatic IRI. In vivo experiments indicated that CD103+ DCs infusion ameliorated IRI-induced liver damage and Treg inhibition. Further investigations demonstrated that FLT3/FLT3L-dependent CD103+ DCs suppressed hepatocyte apoptosis via activation of Treg cells in vitro. CONCLUSION: FLT3/FLT3L-induced CD103+ DCs alleviated hepatic IRI through activating Treg cells.


Assuntos
Antígenos CD/metabolismo , Células Dendríticas/transplante , Cadeias alfa de Integrinas/metabolismo , Fígado/irrigação sanguínea , Proteínas de Membrana/metabolismo , Traumatismo por Reperfusão/terapia , Linfócitos T Reguladores/imunologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Animais , Transplante de Células , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fígado/imunologia , Testes de Função Hepática , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologia
19.
World J Gastroenterol ; 25(28): 3753-3763, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31391770

RESUMO

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.


Assuntos
Veias Hepáticas/patologia , Hepatopatia Veno-Oclusiva/diagnóstico , Plantas Comestíveis/toxicidade , Alcaloides de Pirrolizidina/toxicidade , Anticoagulantes/uso terapêutico , Biópsia , China , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Hidratação/métodos , Glucocorticoides , Veias Hepáticas/citologia , Veias Hepáticas/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/terapia , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Testes de Função Hepática , Transplante de Fígado , Imagem por Ressonância Magnética , Plantas Comestíveis/química , Derivação Portossistêmica Transjugular Intra-Hepática , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Orv Hetil ; 160(32): 1260-1269, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31387372

RESUMO

Introduction: Resecability of liver tumors is exclusively depending on the future liver remnant (FLR). The remnant can be hypertrophised using portal vein occlusion techniques. The latest hypertrophising method is Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS), which provides the most significant induced hypertrophy in the shortest time. Morbidity and mortality of this procedure were initially unacceptably high. Aim: Reducing complications by better patient selection and modified surgical technique. Method: The First Department of Surgery, Semmelweis University, Budapest, prefers the 'no touch' technique, instead of 'complete mobilization'. For optimizing patient selection, an international registry (including our patients' data) was established. In addition to the surgical, we collected demographic, disease, liver function, histology, morbidity (Clavien-Dindo) and mortality parameters. Volume and function measurements were performed by using CT-volumetry and 99mtechnecium-mebrofenin SPECT/CT. Data were analyzed by multivariate analysis (significance: p<0.05). Results: We performed 20 ALPPS procedures from 2012 to 2018. The relative volume increment and resectability in our department and among the 320 registry patients were 96% vs. 86% and 95% vs. 98%. Using 'no touch' technique, the Clavien-Dindo III-IV morbidity and mortality rates were significantly lower (22%-0%) than with 'complete mobilization' (63%-36%) (p<0.05). Based on the multivariate analysis of the registry patients, age over 60 years, liver macrosteatosis, non-colorectal liver tumor, >300 minutes operation time, >2 units of red blood cell transfusion, or insufficient FLR function before stage 2 were identified as independent factors influencing mortality (p<0.05). Conclusion: Mortality and morbidity of ALPPS can be reduced by proper patient selection and 'no touch' surgical technique. Orv Hetil. 2019; 160(32): 1260-1269.


Assuntos
Embolização Terapêutica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Seleção de Pacientes , Veia Porta/cirurgia , Humanos , Ligadura , Fígado/irrigação sanguínea , Neoplasias Hepáticas/epidemiologia , Morbidade , Segurança do Paciente , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
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