RESUMEN
Disrupted redox homeostasis contributes to renal ischemia-reperfusion (IR) injury. Abundant natural products can activate nuclear factor erythroid-2-related factor 2 (Nrf2), thereby providing therapeutic benefits. Methyl eugenol (ME), an analog of the phenolic compound eugenol, has the ability to induce Nrf2 activity. In this study, we investigated the protective effects of ME against renal oxidative damage in vivo and in vitro. An IR-induced acute kidney injury (AKI) model was established in mice. ME (20 mg·kg-1·d-1, i.p.) was administered to mice on 5 consecutive days before IR surgery. We showed that ME administration significantly attenuated renal destruction, improved the survival rate, reduced excessive oxidative stress and inhibited mitochondrial lesions in AKI mice. We further demonstrated that ME administration significantly enhanced Nrf2 activity and increased the expression of downstream antioxidative molecules. Similar results were observed in vitro in hypoxia/reoxygenation (HR)-exposed proximal tubule epithelial cells following pretreatment with ME (40 µmol·L-1). In both renal oxidative damage models, ME induced Nrf2 nuclear retention in tubular cells. Using specific inhibitors (CC and DIF-3) and molecular docking, we demonstrated that ME bound to the binding pocket of AMPK with high affinity and activated the AMPK/GSK3ß axis, which in turn blocked the Nrf2 nuclear export signal. In addition, ME alleviated the development of renal fibrosis induced by nonfatal IR, which is frequently encountered in the clinic. In conclusion, we demonstrate that ME modulates the AMPK/GSK3ß axis to regulate the cytoplasmic-nuclear translocation of Nrf2, resulting in Nrf2 nuclear retention and thereby enhancing antioxidant target gene transcription that protects the kidney from oxidative damage.
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Lesión Renal Aguda , Factor 2 Relacionado con NF-E2 , Ratones , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Eugenol/metabolismo , Eugenol/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Señales de Exportación Nuclear , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Riñón , Antioxidantes/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismoRESUMEN
This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 µmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.
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Eugenol , Daño por Reperfusión , Apoptosis , Células Epiteliales/metabolismo , Eugenol/análogos & derivados , Eugenol/farmacología , Hemo-Oxigenasa 1/metabolismo , Humanos , Hipoxia , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.
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OBJECTIVE: Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As "non-traditional" risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function. METHODS: The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated. RESULTS: (1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor's BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202-0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045-0.747) and P<0.05, OR (95% CI): 0.114 (0.014-0.948), respectively]. CONCLUSION: The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor's age, BMI and pre-existing hypertension.
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Hipertensión , Trasplante de Riñón , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Calcio , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Hipertensión/complicaciones , Biomarcadores , Calcio de la Dieta , LípidosRESUMEN
OBJECTIVE: To summarize the histopathological features of posttransplant complications for renal allografts and evaluate the biopsy values. METHODS: Between January 1997 and May 2010, a total of 1712 percutaneous renal allograft biopsies were performed in 1500 kidney transplants and diagnostic procedures for staining, classification and staging had been performed according to the Banff 1997 and 2005 Schema. RESULTS: There were 213 (14.2%) cases of acute T cell-mediated rejection post transplantation in 1500 kidney transplants. Meanwhile there were 36 (2.4%) cases of acute antibody-mediated rejection. Chronic T cell-mediated rejection and chronic antibody-mediated rejection were 251 (16.7%) cases and 45 (3.0%) cases, respectively. Acute CNI-nephrotoxicity and chronic CNI-nephrotoxicity were 106 (7.1%)cases and 251 (16.7%) cases, respectively. Relapsed or new nephropathy were 6 (0.4%) cases. Chronic CNI-nephrotoxicity is the most common cause of allograft dysfunction in the long survival recipients. CONCLUSION: Percutaneous renal allograft biopsy is valuable for the diagnosis of various posttransplantation complications.
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Trasplante de Riñón/patología , Riñón/patología , Adolescente , Adulto , Anciano , Biopsia con Aguja , Femenino , Rechazo de Injerto/patología , Humanos , Persona de Mediana Edad , Trasplantes , Adulto JovenRESUMEN
OBJECTIVE: To observe the histopathological features of posttransplant complications for hepatic allografts and evaluate their biopsy values. METHODS: From January 1999 to May 2011, a total of 268 percutaneous hepatic allograft biopsies were conducted in 207 recipients and the diagnostic procedures for staining, classification and staging performed according to the Banff schema and Chinese Schema on hepatic allograft rejection. RESULTS: Among them, there were ischemia/reperfusion injury (n = 26, 9.7%), acute T cell-mediated rejection (n = 83, 31.0%), acute antibody-mediated rejection (n = 12, 4.5%), chronic posttransplantation rejection (n = 31, 11.6%), immunosuppressive-induced liver injury (n = 70, 26.1%) and recurrent diseases (n = 18, 6.7%). Acute T cell-mediated rejection and drug-induced liver injury were two most common causes of allograft dysfunctions. CONCLUSION: Percutaneous hepatic allograft biopsy is valuable for the diagnosis and evaluation of various posttransplantation complications.
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Trasplante de Hígado/patología , Hígado/fisiopatología , Complicaciones Posoperatorias , Adolescente , Adulto , Anciano , Biopsia con Aguja , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
20 ml peritoneal lavage fluid of mice infected with Toxoplasma gondii RH strain was diluted to 250 ml with sterilized physiological saline, and filtered through cellulose membrane filters (pore size: 5 microm). The filtrate was centrifuged at 1512 x g for 15 min, and the sediment was pure T. gondii tachyzoites which were then sonicated. The soluble antigen was prepared by centrifugation at 11200 x g for 30 min. Sera of T. gondii infected SD rat and normal SD rats were collected for immunodetection of soluble antigen. The specificity and valence of soluble antigen were detected with indirect ELISA. The mean removal rates of mouse leukocytes and erythrocytes were 99.9% and 80.3%, respectively, and recovery rate of tachyzoites was 71%. The soluble antigen was extracted from purified T. gondii (1.38 mg per mouse). Indirect ELISA showed that the lowest effective antigen concentration was 5 microg/ml.
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Antígenos de Protozoos/aislamiento & purificación , Filtración/instrumentación , Toxoplasma/aislamiento & purificación , Toxoplasmosis Animal/parasitología , Animales , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/inmunología , Ratones , Ratones Endogámicos , Ratas , Ratas Sprague-Dawley , Toxoplasma/inmunologíaRESUMEN
OBJECTIVE: To investigate the role of connective tissue growth factor (CTGF) in epithelial mesenchymal transition of HK-2 cells in vitro. METHODS: HK-2 cells were randomly divided into two groups: (1) control group including cells cultured in DMEM medium supplemented with 10% fetal bovine serum only; and (2) experimental group including cells cultured in DMEM medium supplemented with 10% fetal bovine serum and recombinant CTGF at a final concentration of 5 microg/L. The cells were collected at 72 h time points. Direct immunofluorescence staining and immunohistochemistry were used to evaluate the E-cadherin, Vimentin, alpha-SMA and ERK2 in cells. Western-blotting was used to detect the E-cadherin, Vimentin and ERK2 protein expression. Boyden Chamber was used to detect the migration of tubular endothelium at 1 d, 3 d and 5 d. RESULTS: There were less E-cadherin but more Vimentin expressed in cells of the experimental group. The presence of alpha-SMA was detected at 48 h with peak at 72 h in the cells of the experimental group. On the first day, the cellular migration in the two groups showed no difference. However, after 3 days, the transformed cells migrated surpassed the control group with peak at the 5th day [(45.0+/-1.1):(14.0+/-1.2), P<0.05)]. CONCLUSION: Connective tissue growth factor induces mesenchymal transformation of HK-2 cells, in which the ERK2 signaling pathway may play an important role.
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Cadherinas/metabolismo , Movimiento Celular/efectos de los fármacos , Factor de Crecimiento del Tejido Conjuntivo/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Túbulos Renales Proximales/citología , Actinas/metabolismo , Línea Celular , Células Epiteliales/citología , Células Epiteliales/metabolismo , Humanos , Mesodermo/citología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Distribución Aleatoria , Transducción de Señal , Vimentina/metabolismoRESUMEN
BACKGROUND: Recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation is very common in the absence of adequate prophylaxis and is often associated with poor prognosis because of the development of cirrhosis, fibrosing cholestatic hepatitis, or fulminant hepatitis. Therefore it is important to study the prevention of HBV reinfection after liver transplantation. METHODS: Recombinant Fab (rFab) was constructed to evaluate gene therapy for post-transplantation HBV reinfection. Hepatocytes were divided into three groups: HBV-infection, rFab-blocked HBV-infection, and control. The inhibition of HBsAg adsorption test, the micro-cytotoxicity assay, and the blockade test of HBV infection were carried out. The HBsAg adsorption rate, the hepatocyte death rate and the HBV infection rate were statistically analyzed. RESULTS: The HBsAg adsorption rate blocked by rFab in the HBsAg adsorption test was 0.3%. The hepatocyte death rate was 98.8% induced by rFab in the micro-cytotoxicity assay, 1.3% in the rFab-blocked HBV-infected group and 77% in the HBV-infected group in the blockade test of HBV. CONCLUSIONS: We found that rFab effectively blocked HBV infection in human hepatocytes. This provides an attractive alternative for hepatitis B prophylaxis.
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Anticuerpos Monoclonales/química , Terapia Genética/métodos , Hemoglobinas/inmunología , Virus de la Hepatitis B/metabolismo , Hepatitis B/prevención & control , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Proteínas Recombinantes/química , Adsorción , Colestasis/prevención & control , Fibrosis/prevención & control , Hemoglobinas/química , Hepatitis/prevención & control , Hepatocitos/metabolismo , Humanos , Hígado/inmunologíaRESUMEN
OBJECTIVE: To report the modified technique and the short-term results of simultaneous pancreas-kidney transplantation (SPK) with the enteric drainage (ED) of exocrine secretions. METHODS: From June 2000 to August 2006, thirty-eight patients with diabetes complicated with uremia underwent SPK. The pancreas graft was placed intraperitoneally with exocrine secretions drained into the proximal jejunum without Roux-en-Y procedure. The mean cold ischemic times of pancreas and kidney were (10 +/- 2.0) h and (7 +/- 2.0) h, respectively. Quadruple immunosuppressive therapy with antilymphocyte globulin or anti-CD25 monoclonal antibody, tacrolimus, mycophenolate mofetil and steroids was adopted except one patient. RESULTS: The 6-month survival rates of patients and grafts were both 97.4% after transplantation. All patients achieved insulin-free euglycemia at (7 +/- 6.9) d postoperative except one. For preoperative patients, mean fasting insulin and C-peptide values were (9 +/- 8.1) mU/L and (6 +/- 4.5) mU/L. After operation, fasting insulin and C-peptide values of patients were (12 +/- 5.8) mU/L and (6 +/- 4.7) mU/L, respectively, which peaked to an insulin level of (57 +/- 43.0) mU/L and a C-peptide level of (11 +/- 6.8) mU/L with stimulation. There were eight cases of delayed renal graft function. All other patients achieved immediate renal graft function. No graft losses occurred due to leakage or intra-abdominal infection. The most common surgical complications were wound infection (n = 12), enteric anastomostic hemorrhage (n = 5) and perirenal hemorrhage (n = 2). Three patients (7.9%) had been reoperated for the reasons of intra-abdominal hemorrhage and perirenal hemorrhage. CONCLUSIONS: SPK is an effective treatment option for selected patients with diabetes mellitus and approaching end-stage renal disease. Enteric exocrine drainage by direct side-to-side anastomosis (without Roux-en-Y) seems to be a simple and reliable technique.
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Drenaje/métodos , Yeyuno/cirugía , Trasplante de Riñón/métodos , Trasplante de Páncreas/métodos , Diabetes Mellitus/cirugía , Femenino , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Resultado del Tratamiento , Uremia/cirugíaRESUMEN
OBJECTIVE: To investigate the protective effects on allografts and the possible mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against chronic rejection injury. METHODS: Ex vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed. RESULTS: AdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T cells. CONCLUSIONS: AdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.
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Terapia Genética/métodos , Rechazo de Injerto/prevención & control , Hemo-Oxigenasa 1/genética , Adenoviridae/genética , Animales , Vasos Sanguíneos/trasplante , Recuento de Linfocito CD4 , Enfermedad Crónica , Vectores Genéticos , Rechazo de Injerto/etiología , Supervivencia de Injerto , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Macrófagos/patología , Masculino , Ratas , Ratas Endogámicas Lew , Transfección , Trasplante HomólogoRESUMEN
The dynamic expression of cytokines and phenotypes during the differentiation process of dendritic cell precursors (pre-DCs) to mature dendritic cells (DCs) was investigated, and the effects of inflammatory stimulation with lipopolysaccharide (LPS) on DCs differentiation were understood. The differentiation of bone marrow cells isolated from Balb/c mice was induced to DCs in an 8-day cell culture system with RPMI-1640 complete culture medium containing 10% FBS, 20 ng/mL recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and 10 ng/mL recombinant mouse interleukin-4 (rmIL-4). On the day 3, 6 and 7 after culture, DCs were divided into non-LPS group and LPS group, given 500 ng/mL LPS for 24 h stimulation and no stimulation respectively. The expression levels of CD11c+, MHC-II+, CD40+, CD80+ and CD86+ were detected by flow cytometry, and those of IL-2, IL-4, IL-10, IL-12 p70 and IFN-γ in the supernatant by ELISA. On the day 3 and 6 after culture, the expression of IL-2, IL-4, IL-10 and IFN-γ in DCs showed no significant differences between non-LPS group and LPS group, whereas the differences were significant at day 7. The expression levels of cytokines (for IL-2, IL-4, IL-10, IFN-γ and IL-12 p70: 152.86±6.91, 778.33±8.35, 44.55±2.54, 58.26±1.09 and 2423.00±57.21 pg/mL respectively) in LPS group were higher than those in non-LPS group, especially IL-12 p70 increased obviously at day 7. It was concluded that during the differentiation process of pre-DCs to mature DCs, LPS stimulates DCs producing large amounts of IL-12 p70 and Th1-type cytokines as compared with Th2-type cytokines, and day 7 may be a key time-point for DCs polarization.
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Células de la Médula Ósea/citología , Citocinas/metabolismo , Células Dendríticas/citología , Lipopolisacáridos/farmacología , Animales , Células de la Médula Ósea/inmunología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo/química , Células Dendríticas/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , FenotipoRESUMEN
OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to clarify the immune protection of auxiliary liver to other allograft. METHODS: Immunological markers and pathological changes in 3 patients undergoing auxiliary liver transplantation were analysed. RESULTS: The lower the concentration of immunosuppressive agent, the less the rejection and the milder the intensity in the 3 patients. The function of allograft after auxiliary liver transplantation was excellent. CONCLUSIONS: Patients are in a low immune reaction state after auxiliary liver transplantation. Auxiliary liver can protect other allografts by related immunological mechanisms. The side-effects of low-concentration immunosuppressive agents on auxiliary liver and other allografts are mild.
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Enfermedad del Almacenamiento de Glucógeno/cirugía , Hepatitis/cirugía , Obstrucción Intestinal/cirugía , Intestino Delgado/trasplante , Trasplante de Riñón , Trasplante de Hígado , Adulto , Niño , Resultado Fatal , Enfermedad del Almacenamiento de Glucógeno/mortalidad , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Obstrucción Intestinal/mortalidad , Intestino Delgado/inmunología , Trasplante de Riñón/inmunología , Hígado/inmunología , Trasplante de Hígado/inmunología , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
OBJECTIVE: To present a good tacrolimus (FK506) administration protocol in liver transplantation. METHODS: Fifty liver transplantation patients were classified into FK506 high-concentration (20 patients), FK506 mid-concentration (20), CsA-FK506 (5) and FK506-CsA (5) groups. Clinical manifestations, FK506 side-effects and pathological changes were observed. RESULTS: The FK506 high-concentration group showed complications such as infection and liver function damage. The FK506 mid-concentration group showed excellent therapeutic results and some complications easy to deal with. CONCLUSION: FK506 is a highly effective immunosuppressive agent and the mid-concentration protocol is a better one.
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Inmunosupresores/administración & dosificación , Trasplante de Hígado , Tacrolimus/administración & dosificación , Adolescente , Adulto , Niño , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Concentración Osmolar , Cuidados Posoperatorios , Retratamiento , Tacrolimus/efectos adversosRESUMEN
OBJECTIVE: To explore the changes of mitogen activated protein kinase (MAPK) cascade pathway and anti-stress response of hepatocytes after liver transplantation. METHODS: Ten normal liver specimens and 18 punctured donor liver specimens were divided into 3 groups: A (control:10), B (no rejection:10) and C (acute rejection:8). MAPK, Ras, Jun and heat shock protein 70 (HSP70) were tested immunohistochemically while Ras and HSP70 were tested by in situ hybridization. All sections were subjected to image analysis. RESULTS: Protein expressions of MAPK, Ras and Jun were increased by an ascending order of groups A, B and C. The protein expression of HSP70 was the highest in group B but lower in group C. Expressions of Ras and HSP70 mRNA were consistent with those of protein. CONCLUSIONS: The changes of the MAPK cascade pathway and anti-stress response of hepatocytes after liver transplantation are one of regulation mechanisms for protecting the hepatocytes from damage after liver transplantation. This mechanism is active to support individual survival
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Rechazo de Injerto/fisiopatología , Trasplante de Hígado , Sistema de Señalización de MAP Quinasas/fisiología , Estrés Fisiológico/fisiopatología , Expresión Génica , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Inmunohistoquímica , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
OBJECTIVE: To study the etiology, prevention and management of acute respiratory distress syndrome (ARDS) after liver transplantation. METHODS: The clinical data of 104 patients with end-stage liver diseases who had had liver transplantations were retrospectively reviewed. RESULTS: Seventeen patients (16.3%, 17/104) altogether were diagnosed as having ARDS after liver transplantation. Ten of them developed ARDS within 24 hours, of whom 1 died during the operation, and 7 developed ARDS 3 or 4 days after they were extubated and when methylprednisolone was tapered. Fourteen of the 17 ARDS patients (14/17) were found to have overloaded crystalloid infusion, massive transfusion of blood or blood products such as plasma, platelets, in addition to a prolonged surgical time secondary to serious bleeding during the diseased liver removal without evidence of active infection. One was found to have serious systemic infection and operatively disseminated intravascular coagulation. Four of the recipients developed ARDS suddenly when intravenous cyclosporine was given on the 3rd day after operation. One patient of the 4 had all of the aforementioned conditions. Two patients suffered from gastric aspiration. Five (30%, 5/17) of them survived ARDS with the combined treatment consisting of positive end-expiratory pressure mechanical ventilation suctioning as much edema fluid or sputum as possible, administration of diuretics, bolus of corticosteroids, and culture-based antibiotics. Hemeodialysis was indicated for patients with oliguric renal failure. CONCLUSIONS: ARDS is a serious multifactoral complication after liver transplantation with a high mortality and fatality. The most likely cause is fluid overload from crystalloid liquid infusion or massive transfusion. The other predisposing or contributing factors include sepsis, IV use of cyclosporine, fast tapering of corticosteroids, and gastric aspiration. Other factors such as transfusion-related acute lung injury (TRALI), and reperfusion syndrome of the newly implanted liver may also contribute. Though the treatment should primarily be supportive in nature, it is helpful to understand the predisposing and contributing factors and to aid in prevention, management and treatment.
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Trasplante de Hígado/efectos adversos , Síndrome de Dificultad Respiratoria/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea , Niño , Hemorragia/etiología , Hemorragia/terapia , Humanos , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/prevención & control , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
OBJECTIVES: To explorer the change of several signal pathway and their signal after liver transplantation. METHODS: Classified 34 punctured donor liver samples and 10 normal liver samples as A (no rejection) groups, B (mild/moderate acute rejection) groups, C (serious acute rejection) groups, D (chronic rejection/fibrosis) groups and E (control) groups, MAPK, Ras and p53 were performed immunohistochemistry analysis and image analysis. MAPK and Ras were performed in situ hybridizition. Then image analysis was performed. RESULTS: The protein expression of MAPK, Ras, increase by turns of A, B and C groups (1.42+/-0.28, 3.88+/-0.87, 6.68+/-0.57 in MAPK; 1.27+/-0.12, 2.80+/-0.30, 3.93+/-0.20 in Ras; corresponding), and decrease by turns of D and E groups (1.49+/-0.37, 0.88+/-0.20 in MAPK; 1.47+/-0.21, 1.01+/-0.12 in Ras; corresponding, F=178.39 in MAPK and 320.59 in Ras, groups B, C vs groups A, D, E, P<0.001 in MAPK and Ras), The protein expression of p53 is higher in treated groups (The results of groups A to E are 2.09+/-0.13, 2.39+/-0.11, 2.03+/-0.19, 2.26+/-0.18 and 0.35+/-0.08, corresponding, F=360.08, groups E vs groups A, B, C, D, P<0.001). Expression of MAPK, Ras mRNA is as same as that of protein. CONCLUSION: The MAPKs pathway has role in rejection response after liver transplantation. And it seemed that the MAPKs and p53 are one regulation mechanism for protecting the hepatocyte from damage after liver transplantation.
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Trasplante de Hígado , Transducción de Señal/fisiología , Humanos , Inmunohistoquímica , Hibridación in Situ , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas Activadas por Mitógenos/análisis , Proteína p53 Supresora de Tumor/análisis , Proteínas ras/análisisRESUMEN
Primary hepatic leiomyoma is a neoplasm of mesenchymal origin and occurs only rarely. Secondary to benign smooth muscle proliferation, it is usually found in adult women and is associated with Epstein-Barr virus (EBV) infection. Here, we report the 29(th) case of primary hepatic leiomyoma with its unique features related to diagnosis, treatment and developmental biology. A 48-year-old man, with an immunocompromised status, complained of pain in the upper quadrant of the abdomen. Serological analysis indicated no presence of hepatitis virus, no human immunodeficiency virus, and no EBV infection. The levels of α-fetoprotein and carcinoembryonic antigen were normal. A mass was detected in segment III of the hepatic lobe by ultrasonography and an abdominal computed tomography scan. Endoscopy had negative findings. Exploratory laparotomy found no existing extrahepatic tumor and left lateral lobectomy was performed. Pathological examination showed the mass to be a typical leiomyoma. The cells were positive for α-smooth muscle actin and desmin, and negative for the makers of gastrointestinal stromal tumor (GIST), including CD117, CD34 and DOG1 (discovered on GIST1). In situ hybridization revealed negative status for EBV-encoded small RNA. After left lateral lobectomy, the patient was not given chemotherapy or radiotherapy. During a 2-year follow-up, no sign of local recurrence or distant metastasis was observed. In conclusion, we report a rare case of primary hepatic leiomyoma in a male patient without EBV infection. Hepatic resection was curative. This case presents data to expand our knowledge concerning the complex and heterogeneous nature of primary liver leiomyoma, indicating that EBV infection is important but neither necessary nor sufficient for the development of primary liver leiomyoma.
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Herpesvirus Humano 4/aislamiento & purificación , Leiomioma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Hepatectomía , Humanos , Leiomioma/cirugía , Hígado/microbiología , Hígado/cirugía , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Living donor kidney transplantation (LKT) has been booming in China. This study aimed to elucidate the renal function of both Chinese donors and recipients after the donation and transplantation. METHODS: One hundred and forty-one pairs of donors and recipients for LKT were randomly selected and followed up for up to seven years. The donors' and recipients' renal function was recorded before and after operation. RESULTS: The donors presented a mean age of (43.9 ± 7.5) years at donation. The female contributed 101/141 (71.6%) in all donors, and no effect was shown between genders on healthy donors' renal function. The donors' glomerular filtration rates (GFR) were (119.5 ± 20.4) ml/min, (85.2 ± 17.6) ml/min, (87.2 ± 15.9) ml/min, (82.1 ± 14.6) ml/min and (83.0 ± 13.7) ml/min preoperatively, and for five days, three months, one year and beyond one year after the operation. The donors for the period of 1 - 3 years, 3 - 5 years and more than 5 years after donation showed GFR as (83.9 ± 12.7) ml/min, (83.0 ± 17.6) ml/min, and (80.9 ± 20.8) ml/min, respectively, no statistically significant difference was found. Moreover, no significant clinical changes in blood pressure and proteinuria were found among the donors. In the recipients, delayed graft function (DGF) rate was 6.4%, acute rejection rate was 11.3%, and GFR were (66.5 ± 16.4) ml/min, (73.2 ± 19.6) ml/min and (63.9 ± 18.6) ml/min respectively at three months, one year and beyond one year post-transplantation respectively. CONCLUSION: The donors/recipients of LKT in Chinese population experience well-functioning remaining/donor kidneys.
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Trasplante de Riñón , Donadores Vivos , Adulto , Anciano , Presión Sanguínea/fisiología , China , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Proteinuria/fisiopatologíaRESUMEN
Combined en bloc liver/pancreas transplantation (CLPT) was used primarily in the treatment of otherwise non-resectable upper abdominal malignancy. In fact, a more appropriate indication is in patients with liver disease and insulin-dependent diabetes mellitus (IDDM). Here, we report on two successful cases of CLPT at our hospital. One was a patient with non-resectable advanced liver cancer. The recipient survived for 23 mo and finally died of recurrent tumor. The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM. We performed CLPT with a modified surgical technique of preserving the native pancreas. He is currently liver-disease- and insulin-free more than 27 mo post-transplant. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modification of the surgical procedure.