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1.
Transpl Int ; 22(11): 1100-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19663939

RESUMO

Reperfusion injury remains one of the major problems in transplantation. Free radicals and disturbance of microcirculation are the supposed main contributors. Recent evidence shows that Danshen, a traditional Chinese drug used in vascular diseases, can scavenge radicals and improve microcirculation. This study investigates its effect on liver transplantation (LTx). Before organ recovery, female Sprague-Dawley rats (210-240 g) received intravenous Danshen or the same volume of Ringer solution as control. LTx was performed after 1 h of cold storage. Microperfusion, leukocyte-endothelium interaction and latex-bead phagocytosis were evaluated with in vivo microscopy. Survival, transaminases and histology were assessed. Immunohistology was used for TNF-alpha levels. anova and Fisher's exact test were employed for statistical analyses as appropriate. Survival increased from 60% in controls to 100% (P < 0.05). AST and LDH decreased from 3969 +/- 1255 U/l and 15444 +/- 5148 U/l in controls to 1236 +/- 410 U/l and 5039 +/- 1594 U/l, respectively (P < 0.05). In vivo microscopy revealed decreased leukocyte-adherence and increased blood flow velocity in sinusoidal zones after administration of Danshen (P < 0.05), while latex-bead phagocytosis was found in 60% of controls (P < 0.05). The TNF-alpha index decreased from 2.08 +/- 0.09 in controls to 1.09 +/- 0.09 (P < 0.05). This study clearly demonstrates hepatoprotective effects after experimental LTx, which can be explained via anti-oxidative effects, improved microcirculation and decreased Kupffer cell activation.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Transplante de Fígado , Fígado/irrigação sanguínea , Fitoterapia , Complicações Pós-Operatórias/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Salvia miltiorrhiza , Animais , Adesão Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/fisiopatologia , Feminino , Sequestradores de Radicais Livres/farmacologia , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/imunologia , Leucócitos/fisiologia , Fígado/ultraestrutura , Microcirculação/efeitos dos fármacos , Microesferas , Estresse Oxidativo/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Fator de Necrose Tumoral alfa/análise
2.
Transpl Int ; 22(2): 232-41, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18954374

RESUMO

Danshen (DS) is used for treatment of various ischemic events in the traditional Chinese medicine. Hence, this study was designed to investigate its effect on ischemia/reperfusion injury (IRI) after experimental kidney transplantation (eKTx). Nephrectomized Sprague-Dawley rats underwent eKTx. Some animals were infused with 1.5 ml DS 10 min before surgery. Kidney grafts were transplanted after cold storage for 20 h in Histidine-Tryptophane-Ketoglutarate solution. After reperfusion blood samples were collected for blood urinary nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and alanine transaminase. Further, tissue was assessed for morphologic and pathophysiologic changes. Donor preconditioning with DS (DS-d) significantly decreased BUN, creatinine, LDH, and aspartate aminotransferase to 65-97% of controls while preconditioning of the recipient (DS-r) decreased values to 58-82% (P < 0.05). Tubular damage and caspase-3 decreased significantly in both DS-d and DS-r (DS-d: 96% and 67%, DS-r: 83% and 75% of controls) while heat shock protein 72 and superoxide dismutase increased significantly (DS-d: 143% and 173%, DS-r: 166% and 194% of controls). Further, inducible nitric oxide synthase and tumor necrosis factor-alpha decreased (DS-d: 84% and 61%, DS-r: 79% and 67% of controls) after DS. Preconditioning of both donors and recipients with DS significantly reduces IRI and thus improves graft function after eKTx.


Assuntos
Nefropatias/prevenção & controle , Transplante de Rim/efeitos adversos , Fitoterapia , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Salvia miltiorrhiza , Animais , Modelos Animais de Doenças , Feminino , Nefropatias/etiologia , Raízes de Plantas , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia
3.
J Surg Res ; 146(1): 127-34, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18061615

RESUMO

BACKGROUND: Ischemia/reperfusion injury is a major problem in clinical transplantation (Tx). Taurine has been shown to protect liver grafts from ischemia/reperfusion injury after Tx. Thus, this study was designed to evaluate its effect on kidney grafts after transplantation. MATERIALS AND METHODS: Various concentrations of taurine were infused before donor nephrectomy (1.5 mL; 30, 100, 300 mM). Controls were given the same volume of Ringers' solution. Subsequently, grafts were cold-stored for 19 h in histidine-tryptophan-ketoglutarate solution and transplanted. Six hours after Tx, graft function and injury were assessed with blood urea nitrogen/creatinine and aspartate aminotransferase/lactate dehydrogenase. Graft biopsies were taken to evaluate tubular damage, caspase-3, superoxide dismutase, and heat shock protein 72 (HSP-72) to index necrosis, apoptosis, antioxidative capacity, and regeneration, respectively. RESULTS: Taurine significantly decreased blood urea nitrogen, creatinine, aspartate aminotransferase, and lactate dehydrogenase in a dose-dependent manner to up to 71%, 69%, 51%, and 53% of controls, respectively. Further, tubular damage and caspase-3 expression decreased to 44% and 18% of control values (P < 0.01), while superoxide dismutase and heat shock protein 72 expression increased by 95% and 77% of controls, respectively (P < 0.05). CONCLUSIONS: This study demonstrates that donor preconditioning with taurine protects kidney grafts from injury (apoptosis, necrosis), improves graft function, and increases the regenerative potential most likely via mechanisms including antioxidation.


Assuntos
Transplante de Rim/métodos , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Taurina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biópsia , Caspase 3/metabolismo , Relação Dose-Resposta a Droga , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Proteínas de Choque Térmico HSP72/metabolismo , Rim/metabolismo , Rim/patologia , Transplante de Rim/patologia , Modelos Animais , Necrose/patologia , Necrose/prevenção & controle , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismo
4.
World J Gastroenterol ; 12(22): 3597-601, 2006 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-16773718

RESUMO

AIM: To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal (UGI) bleeding under today's therapeutic regimen. METHODS: From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients' data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis: age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time (PT), gastric ulcer (small curvature), duodenal ulcer (bulbus back wall), Forrest classification, vascular stump, variceal bleeding, Mallory-Weiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS: Seventy male (58%) and 51 female (42%) patients with a median age of 70 (range: 21-96) years were treated. Their in-hospital mortality was 14%. While 12% (11/91) of the patients died after conservative therapy, 20% (6/30) died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer (n = 36; 30%), gastric ulcer (n = 35; 29%), esophageal varicosis (n = 12; 10%), Mallory-Weiss syndrome (n = 8; 7%), erosive lesions of the mucosa (n = 20; 17%), cancer (n = 5; 4%), coagulopathy (n = 4; 3%), lymphoma (n = 2; 2%), benign tumor (n = 2; 2%) and unknown reason (n = 1; 1%). A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer (bulbus back wall) were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer (bulbus back wall) and patients' gender (male) were of prognostic importance for the clinical outcome (mortality) of patients with a bleeding ulcer. CONCLUSION: Most prognostic parameters used in clinical routine today are not reliable enough in predicting a patient's vital threat posed by an UGI bleeding. Liver cirrhosis, on the other hand, is significantly more frequently associated with an increased risk to die after bleeding of an ulcer located at the posterior duodenal wall.


Assuntos
Úlcera Duodenal/complicações , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Cirrose Hepática/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Úlcera Duodenal/patologia , Feminino , Hemorragia Gastrointestinal/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
5.
Clin Transplant ; 20(2): 151-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16640519

RESUMO

Liver transplantation (LT) in an adult with situs inversus (SI) is extremely rare and requires precise pre-operative management. A 48-yr-old male with SI suffering from alcoholic liver cirrhosis underwent LT at our institution in March 2003. Pre-operatively, liver anatomy was determined by CT scan, three-dimensional liver reconstruction and angiography. LT was performed using the Belghiti technique with side-to-side cavo-caval anastomosis, transplanting a graft from a donor with normal anatomy. Post-operatively, the patient recovered without major complications, except an epileptic event because of a central pontine myelinolysis, and he was discharged on the 25th post-operative day. Three months after surgery, the T-drain placed intra-operatively into the donor bile duct was removed; transplant perfusion and function were stable with an actual follow-up period of 24 months. LT in patients with SI is feasible. Pre-operative imaging with three-dimensional reconstruction is a beneficial tool for operation planning in patients with rare anatomic variations.


Assuntos
Transplante de Fígado/métodos , Situs Inversus/cirurgia , Hepatectomia/métodos , Encefalopatia Hepática/cirurgia , Humanos , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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