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1.
Am J Physiol Cell Physiol ; 316(3): C299-C311, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462539

RESUMO

Hepatocellular carcinoma (HCC) is known for its high mortality rate worldwide. Based on intensive studies, microRNA (miRNA) expression functions in tumor suppression. Therefore, we aimed to evaluate the contribution of miR-146a-5p to radiosensitivity in HCC through the activation of the DNA damage repair pathway by binding to replication protein A3 (RPA3). First, the limma package of R was performed to differentially analyze HCC expression chip, and regulative miRNA of RPA3 was predicted. Expression of miR-146a-5p, RPA3, and DNA damage repair pathway-related factors in tissues and cells was determined. The effects of radiotherapy on the expression of miR-146a-5p and RPA3 as well as on cell radiosensitivity, proliferation, cell cycle, and apoptosis were also assessed. The results showed that there exists a close correlation between miR-146a and the radiotherapy effect on HCC progression through regulation of RPA3 and the DNA repair pathway. The positive rate of ATM, pCHK2, and Rad51 in HCC tissues was higher when compared with that of the paracancerous tissues. SMMC-7721 and HepG2 cell proliferation were significantly inhibited following 8 Gy 6Mv dose. MiR-146a-5p restrained the expression of RPA3 and promoted the expression of relative genes associated with the DNA repair pathway. In addition, miR-146a-5p overexpression suppresses cell proliferation and enhances radiosensitivity and cell apoptosis in HCC cells. In conclusion, the present study revealed that miR-146a-5p could lead to the restriction of proliferation and the promotion of radiosensitivity and apoptosis in HCC cells through activation of DNA repair pathway and inhibition of RPA3.


Assuntos
Carcinoma Hepatocelular/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Tolerância a Radiação/genética , Adulto , Idoso , Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Células Hep G2 , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética
2.
World J Gastroenterol ; 23(47): 8432-8436, 2017 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-29308003

RESUMO

Wernicke encephalopathy (WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported after liver transplantation. Here, we report a case of a 45-year-old nonalcoholic male patient who developed psychiatric and neurological disturbance 15 d after receiving orthotopic liver transplantation because of hepatitis B-related cirrhosis and portal hypertension. Brain magnetic resonance imaging (MRI) showed symmetric high-signal intensities in the periaqueductal area. The patient was diagnosed with WE and given intravenous high-dose vitamin B1 immediately. His neurological disturbance resolved in 7 d after receiving the vitamin B1. Brain MRI after 5 mo showed nearly complete recovery. Most WE cases may be misdiagnosed in patients after liver transplantation, and we should pay more attention to its onset.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complexo Vitamínico B/uso terapêutico , Encefalopatia de Wernicke/etiologia , Administração Intravenosa , Encéfalo/diagnóstico por imagem , Humanos , Testes de Função Hepática , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Tiamina/uso terapêutico , Deficiência de Tiamina/sangue , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/tratamento farmacológico , Deficiência de Tiamina/etiologia , Encefalopatia de Wernicke/sangue , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico
3.
Hepatobiliary Pancreat Dis Int ; 14(3): 263-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26063026

RESUMO

BACKGROUND: Portal hypertension is one of the most important clinical conditions that cause intraoperative intensive hemorrhage in cirrhotic patients undergoing liver transplantation. Pre-transplant portal decompression may reduce the intraoperative bleeding during liver transplantation. METHODS: Splenic artery trunk embolization (SATE) was performed one month prior to liver transplantation. Platelet count, prealbumin, international normalized ratio, and blood flow in the portal vein and hepatic artery were monitored before and one month after SATE. The measurements above were collected on admission and before surgery in the non-SATE patients, who served as controls. We also recorded the intraoperative blood loss, operating time, required transfusion, post-transplant ascites, and complications within three months after operation in all patients. RESULTS: SATE significantly reduced portal venous blood flow, increased hepatic arterial blood flow, normalized platelet count, and improved prealbumin and international normalized ratio in the patients before liver transplantation. Compared to the non-SATE patients, the pre-transplant SATE significantly decreased the operating time, intraoperative bleeding, post-transplant ascites and severe surgical complications. CONCLUSION: Pre-transplant SATE decreases portal pressure, improves liver function reserve, and reduces the surgical risk of liver transplantation effectively in patients with severe portal hypertension.


Assuntos
Embolização Terapêutica/métodos , Hipertensão Portal/terapia , Transplante de Fígado/efeitos adversos , Cuidados Pré-Operatórios/métodos , Artéria Esplênica , Adulto , Ascite/etiologia , Ascite/prevenção & controle , Biomarcadores/sangue , Coagulação Sanguínea , Velocidade do Fluxo Sanguíneo , Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica/efeitos adversos , Feminino , Artéria Hepática/fisiopatologia , Artéria Hepática/cirurgia , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/fisiopatologia , Coeficiente Internacional Normatizado , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Contagem de Plaquetas , Pressão na Veia Porta , Veia Porta/fisiopatologia , Veia Porta/cirurgia , Pré-Albumina/metabolismo , Cuidados Pré-Operatórios/efeitos adversos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
4.
J Breast Cancer ; 16(1): 77-83, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23593086

RESUMO

PURPOSE: This study aims to analyze the clinical-pathological characteristics of multifocal and multicentric breast cancer (MMBC) in Chinese women. METHODS: Sixty-seven cases with MMBC were randomly collected and reviewed at seven hospitals in representative districts of China during 1999 to 2008. RESULTS: The incidence of MMBC in breast cancer in China was 1.75%. Compared to those with unifocal breast cancer, women with MMBC were more likely to have larger tumor size, lymph node metastasis (59.70% vs. 45.62%) and stage III to IV (46.26% vs. 21.10%). The peak age at onset of MMBC was 40 to 49 years old and has been gradually increasing during 1999 to 2008. Most of the MMBC women were treated with surgery and adjuvant therapy. CONCLUSION: In China, the incidence of MMBC in breast cancer is significantly lower than that in Western countries. Compared to unifocal breast cancer, MMBC is biologically more aggressive. Most MMBC women underwent mastectomy, instead of breast conservation surgery.

5.
Asian Pac J Trop Med ; 5(12): 970-2, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23199716

RESUMO

OBJECTIVE: To observe the effect of Kupffer cells on immune tolerance in liver transplantation. METHODS: The rats were randomly divided into A, B and C groups. A group was sham operation group. The donor rats of group B had intraperitoneal injection of 1 nmol Kuppffer cells every other day for three days before liver transplantation. Rats of group C were injected with equal saline. The rat liver transplantation models were established by modified Kamada's two-cuff technique. The rats were sacrificed after 24 hours. The concentrations of ALT and AST in serum were measured with the biochemical analyzer. The level of IL-2 and TNF-α in serum were measured by ELISA method. The apoptotic indexes were detected by immunohistochemical assay. RESULTS: The concentration of ALT, AST, IL-1 and TNF-α in A, B and C groups were increased successively. The levels of group C were significantly higher than that of group B and A (P<0.05), and the levels of group B were significantly higher than that of group A (P<0.05). The apoptotic indexes of three groups were 3.40±0.37, 14.70±2.54 and 26.33±3.65, respectively, with significant difference among three groups (P<0.05). CONCLUSIONS: Pretreatment with Kupffer cells can reduce liver injury and raise liver transplantation immune tolerance.


Assuntos
Macrófagos do Fígado/imunologia , Macrófagos do Fígado/transplante , Transplante de Fígado/imunologia , Transplante de Fígado/métodos , Alanina Transaminase/sangue , Animais , Apoptose/fisiologia , Aspartato Aminotransferases/sangue , Distribuição de Qui-Quadrado , Tolerância Imunológica , Interleucina-1/sangue , Fígado/química , Fígado/imunologia , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
6.
Mol Biol Rep ; 39(8): 8265-75, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22707142

RESUMO

To investigate the association between p53 codon 72 polymorphisms and gastric cancer risk, a meta-analysis published in 2007 was updated with new data. Relevant literature was retrieved by searching PubMed and statistical analysis conducted using Review Manager software. Twenty-eight case-control studies were included in this meta-analysis, with 6,859 cases and 9,277 controls. The pooled results for all included studies showed that patients with gastric cancer had a borderline lower frequency of the Arg/Arg phenotype (odds ratio (OR) = 0.91, 95 % CI = 0.83-1.00, p = 0.04). When stratified for race, the difference in Arg/Arg frequency was significant among Asians (OR = 0.87, 95 % CI = 0.78-0.97, p = 0.01). On stratifying the various studies we found that, among Asians: (i) patients with cardial gastric cancer had a significantly higher frequency of the Pro/Pro genotype (OR = 1.35, 95 % CI = 1.03-1.77, p = 0.04) than those with non-cardial gastric cancer; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.30, 95 % CI = 1.06-1.61, p = 0.01) than those with early (stage I/II) cancer; and (iii) patients with metastasis had a significantly higher frequency of Pro/Pro (OR = 3.31, 95 % CI = 1.31-8.41) than those without metastasis. Our study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.


Assuntos
Códon , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética , Genótipo , Humanos , Neoplasias Gástricas/etnologia
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(8): 1374-7, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21868327

RESUMO

OBJECTIVE: To investigate the role of Thl7 cells and the cytokine interleukin-17 (IL-17) in acute allograft rejection in mice. METHODS: Mouse models of kidney transplantation were randomly divided into rejection group and isograft group. On the post-operative day (POD) 3 and 7, we tested the serum IL-17 level using enzyme-linked immunosorbent assay and measured the number of Th17 cells in the renal grafts by flow cytometry. The grafts were harvested and fixed in 10% formalin to prepare paraffin sections for routine pathological inspection. RESULTS: Compared to isograft group, the allograft group showed a significantly higher level of serum IL-17 on POD3 and POD7 (P<0.05), and the level of IL-17 is significantly higher on POD7 than on POD3 (P<0.05). The allograft group showed more infiltrating Th17 cells in the grafts on POD3 and POD7 (P<0.05), and the cell number was significantly greater on POD7 (P<0.05). Pathological examination also showed an increased severity of graft rejection with the post-transplantation time. CONCLUSION: Thl7 cells may play an important role in the development of renal graft rejection. IL-17 may serve as a potential specific indicator for predicting allograft rejection.


Assuntos
Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Interleucina-17/sangue , Transplante de Rim/efeitos adversos , Células Th17/imunologia , Animais , Transplante de Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante Homólogo
8.
Hepatobiliary Pancreat Dis Int ; 9(2): 144-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20382584

RESUMO

BACKGROUND: Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. This study was designed to investigate the protective effects of adenovirus-mediated human IL-10 (Ad-hIL-10) gene transfer on protecting grafts from cold ischemia-reperfusion injury following orthotopic liver transplantation in rats. METHODS: Adenoviruses encoding hIL-10 or beta-galactosidase (Ad-lacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48 hours after transduction, and stored for 12 hours at 4 degree centigrade in lactated Ringer's solution prior to transplantation. The rats were divided into saline, Ad-lacZ, and Ad-hIL-10 groups. Liver function test, histopathological examination, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blotting were performed at 24 hours after transplantation in the three groups. RESULTS: Liver function (ALT and AST) was significantly improved, and the Suzuki score was significantly decreased in the Ad-hIL-10 group. The levels of hepatic TNF-alpha, MIP-2, ICAM-1 mRNA, and NF-kappaB protein in the Ad-hIL-10 group were significantly decreased. The expression of hIL-10 mRNA was detected by RT-PCR in Ad-hIL-10-treated grafts but not in controls treated with saline or Ad-lacZ. CONCLUSIONS: Donor pretreatment with Ad-hIL-10 down-regulates the expression of proinflammatory cytokines TNF-alpha, MIP-2, and ICAM-1 mRNA. hIL-10 protects against hepatic cold ischemia-reperfusion injury, at least in part, by suppressing NF-kappaB activation and subsequent expression of proinflammatory mediators.


Assuntos
Adenoviridae/genética , Terapia Genética , Interleucina-10/genética , Isquemia/complicações , Transplante de Fígado/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Animais , Vetores Genéticos , Humanos , NF-kappa B/fisiologia , Ratos , Ratos Sprague-Dawley , Transplante Homólogo
9.
Eur Surg Res ; 44(3-4): 133-41, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20203519

RESUMO

BACKGROUND/AIMS: Gene therapy can provide a possible avenue in organ transplantation to treat acute allograft rejection. This study was designed to investigate the effect of adenovirus-mediated human IL-10 (hIL-10) gene transfer on the apoptosis of infiltrating lymphocytes and examine the efficacy of hIL-10 gene transfer in combination with subtherapeutic doses of cyclosporine A (CsA) in a rat liver transplantation model. METHODS: Inbred male DA and LEW rats were used for liver donors and recipients, respectively. The rats were divided into saline, Ad-lacZ, CsA, Ad-hIL-10 and Ad-hIL-10 + CsA groups. Graft survival, histopathological, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction and flow cytometry were performed in liver specimens obtained from different time points after transplantation in the 5 groups. RESULTS: Ad-hIL-10 pretreatment inhibited allograft rejection, prolonged the survival of hepatic allografts, and downregulated the expression of IFN-gamma and IL-2 mRNA, with simultaneous upregulation of IL-4 mRNA. In addition, Ad-hIL-10 pretreatment upregulated the expression of Fas mRNA in the isolated graft-infiltrating lymphocytes and induced graft-infiltrating lymphocyte apoptosis. A single subtherapeutic dose of CsA acted synergistically with it. CONCLUSION: hIL-10 gene therapy induced alloreactive lymphocyte apoptosis via Fas/FasL pathway. hIL-10 gene transfection in combination with subtherapeutic doses of CsA facilitates the long-term survival of liver grafts.


Assuntos
Interleucina-10/genética , Transplante de Fígado/imunologia , Transplante de Fígado/patologia , Linfócitos/imunologia , Linfócitos/patologia , Adenoviridae/genética , Animais , Apoptose , Sequência de Bases , Primers do DNA/genética , Terapia Genética , Vetores Genéticos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Humanos , Interleucina-10/sangue , Interleucina-10/uso terapêutico , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Transfecção , Transplante Homólogo
10.
J Surg Res ; 157(1): e71-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19555976

RESUMO

BACKGROUND: Apoptosis as well as necrosis may play an important role in hepatic ischemia/reperfusion (I/R) injury. Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. The study focused on cytoprotective and antiapoptotic pathways to assess mechanisms by which gene transduction of human IL-10 (hIL-10) may renders grafts resistant to the cold I/R injury. MATERIALS AND METHODS: Adenoviruses encoding hIL-10 or beta-galactosidase (LacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48h after transduction, and stored for 12h at 4 degrees C lactated Ringer's solution prior to being transplanted. Graft survival, liver function, the degree of necrosis and apoptosis, and the molecules of apoptotic networks were assessed. RESULTS: Ad-hIL-10 pretreatment significantly prolonged the survival of liver grafts by improving liver function, preserving hepatocyte integrity and architecture, and depressing intrahepatic apoptosis and necrosis. In addition, Ad-hIL-10 pretreatment diminished the release of cytochrome c from mitochondria into cytoplasm and caspase-3 activity, with simultaneous up-regulated of antioxidant HO-1 and anti-antiapoptotic Bcl-2 molecules. CONCLUSION: Adenoviral gene transfer of hIL-10 ameliorated cold I/R injury by decreasing hepatic necrosis and apoptosis. The underlying mechanism of cytoprotective effects may at least be involved with the inhibition of caspase-3 activity and mitochondrial cytochrome c release, and the up-regulation of antiapoptotic (Bcl-2) and antioxidant (HO-1) molecules.


Assuntos
Temperatura Baixa , Terapia Genética/métodos , Interleucina-10/genética , Transplante de Fígado , Traumatismo por Reperfusão/prevenção & controle , Adenoviridae/genética , Animais , Apoptose/imunologia , Crioprotetores , Citocromos c/metabolismo , Sobrevivência de Enxerto/fisiologia , Hepatócitos/patologia , Hepatócitos/fisiologia , Humanos , Interleucina-10/imunologia , Necrose , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(3): 524-6, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17611339

RESUMO

OBJECTIVE: To review the surgical treatment for reconstructing hypopharynx and cervical esophagus after hypopharyngo-oesophagectomy, and to evalue its efficacy. METHODS: Different methods were adopted to reconstruct the hypopharynx and cervical esophagus among 25 cases, including 14 cases of carcinoma of the hypopharynx and 11 of carcinoma of hypopharynx and cervical esophagus. In accordance with the standard of the International Union Against Cancer in 1997, the 25 cases were divided into different clinic stages, among which 5 were in T(2)N(0), 2 in T(2)N(1), 4 in T(3)N(0), 3 in T(3)N(1), 7 in T(4)N(1) and 3 in T(4)N(2). Treatment protocol was as follow: Pure operation for 5 cases, re-operation after radiotherapy for 2 cases, operation plus radiotherapy for 18 cases, laryngeal conservation operation for 8, and neck dissection for 21 cases. Reconstruction was done by using free jejunal transplantation, gastric pull-up, the laryngotracheal flap, and myocutaneous flap. RESULTS: After the reconstruction, 3 cases of free jejunal graft and gastric pull-up, 4 of laryngotracheal flap recovered oral fleeding within 2 weeks. No serious complications occurred. After 18 cases underwent the myocutaneous flap reconstruction, no complications occurred in 10 patients, but there were different complications in 8 cases, including pharyngocutaneous fistula (6 cases), haryngoesphageal stenosis (7 cases), and pectoralis major myocutaneous flap necrotic (1 case). The 3-year survival rate was 38.9% (7/18). CONCLUSION: Reconstruction with free jejunal graft, gastric pull-up, and laryngotracheal flap constitutes is a safe and reliable method to restore the continuity of the upper digestive tract after pharyngo-laryngo-oesophagectomy. After the reconstruction with myocutaneous flap, there is high incidence of pharyngocutaneous fistula and haryngoesophageal stenosis.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagoplastia/métodos , Neoplasias Hipofaríngeas/cirurgia , Hipofaringe/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/cirurgia , Esôfago/cirurgia , Feminino , Humanos , Jejuno/transplante , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Reconstrutivos/métodos , Retalhos Cirúrgicos
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(5): 792-6, 2006 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-17062954

RESUMO

OBJECTIVE: To explore the protective effect of octreotide on liver warm ischemia-reperfusion injury and its possible mechanism. METHODS: Pringle's maneuver liver ischemia-reperfusion models were established. Forty eight male Sprague Daweley rats were randomly divided into a sham operation group (S group, n=16), an ischemia-reperfusion group (I/R group, n=16) and an octreotide preconditioning group (OPC group, n=16). ALT and AST in the serum were measured at 30 min after the ischemia and 120 min after the reperfusion. The histomorphological changes and ultrastructure of hepatocellular were observed by optic and transmission electronic microscope. Hepatic adenine nucleotide levels and energy changes (EC) were determined by high performance liquid chromatography (HPLC). RESULTS: (1) At 30 min after the ischemia and 120 min after the reperfusion, the levels of ALT and AST in the serum of OPC group was lower than those in I/R group, whereas the levels of ATP and EC in the hepatic tissue were higher than those in the I/R group (P<0.01 or P<0.05). Compared with the I/R group, the injury of hepatocellular histomorphology and ultrastructure in the OPC group was abated. (2) At 30, 60, and 120 min after the reperfusion, the levels of ATP and EC in the OPC groups were higher than those in the I/R group. During the ischemia, the levels of ATP and EC in the OPC group dropped more slowly than those in the I/R group, but ATP and EC in the OPC groups rose more quickly than those in the I/R group during the reperfusion. CONCLUSION: Octreotide precondition can improve the hepatocellular energy reserve, and protect the liver from warm ischemia-reperfusion injury. The protective of octreotide on warm ischemia-reperfusion injury may be related to its influence on endocrine secretion.


Assuntos
Fígado/irrigação sanguínea , Octreotida/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Temperatura Alta , Masculino , Octreotida/uso terapêutico , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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