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1.
Transplant Proc ; 47(3): 733-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25891721

RESUMO

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is a definitive treatment for type 1 diabetics with end-stage renal disease (ESRD). Because of the shortage of deceased donors in Japan, the mortality rate during the waiting period is high. We evaluated mortality risk in patients with type 1 diabetes waiting for SPK, and the benefit of living-donor kidney transplantation (LDK) preceding pancreas transplantation, which may reduce mortality in patients awaiting SPK. METHODS: This retrospective study included 71 patients with type 1 diabetes. Twenty-six patients underwent SPK, 15 underwent LDK, and 30 were waiting for SPK. Their cumulative patient and graft survival rates were retrospectively evaluated. Risk factors contributing to mortality in patients with type 1 diabetes awaiting SPK were evaluated with the use of a Cox proportional hazards model. RESULTS: The 5-year cumulative patient survival rates in the SPK and LDK groups were 100% and 93.3%, respectively (P = .19), and 5-year kidney graft survival rates were 95.7% and 100% (P = .46), respectively. The cumulative survival rate in patients awaiting SPK was 77.7% at 5 years after registration. Duration of dialysis was the only factor significantly associated with patient and graft survivals according to both univariate and multivariate analyses. CONCLUSIONS: Patient and graft survival rates were similar in the SPK and LDK groups, but the survival rate of patients awaiting SPK decreased over time. Duration of dialysis was an independent risk factor for patient and graft survival. LDK preceding pancreas transplantation may be an effective therapeutic option for patients with type 1 diabetes and ESRD.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores Vivos , Transplante de Pâncreas/métodos , Adulto , Idoso , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Feminino , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Transplante de Pâncreas/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
2.
Transplant Proc ; 47(3): 608-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25817610

RESUMO

BACKGROUND: Renal transplantation has been established as a treatment for end-stage renal disease (ESRD) due to diabetic nephropathy. However, few studies have focused on the outcome after renal transplantation in patients with ESRD and type 2 diabetic nephropathy. To investigate the effect of renal transplantation on ESRD with type 2 diabetic nephropathy, we retrospectively analyzed patients who received renal transplantation at our facility. This study aimed to compare the outcome of renal transplantation for type 2 diabetic nephropathy with that for nondiabetic nephropathy. METHODS: We studied 290 adult patients, including 65 with type 2 diabetic nephropathy (DM group) and 225 with nondiabetic nephropathy (NDM group), who underwent living-donor renal transplantation at our facility from February 2008 to March 2013. We compared the 2 groups retrospectively. RESULTS: In the DM and NDM groups, the 5-year patient survival rates were 96.6% and 98.7%, and the 5-year graft survival rates were 96.8% and 98.0%, respectively, with no significant differences between the groups. There were no significant differences in the rates of surgical complications, rejection, and infection. The cumulative incidence of postoperative cardiovascular events was higher in the DM group than in the NDM group (8.5% vs 0.49% at 5 years; P = .002). CONCLUSIONS: Patient and graft survival rates after renal transplantation for type 2 diabetic nephropathy are not inferior to those for recipients without diabetic nephropathy. Considering the poor prognosis of patients with diabetic nephropathy on dialysis, renal transplantation can provide significant benefits for these patients.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Transplante de Rim/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
3.
Transplant Proc ; 46(2): 395-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24655972

RESUMO

BACKGROUND: Once-daily extended-release tacrolimus (Tac-QD) has been shown to have equivalent efficacy and safety to the twice-daily formulation (Tac-BID) in kidney transplant patients. However, detailed comparison of allograft pathology found on a protocol biopsy (PB) in Tac-QD- versus Tac-BID-based regimens has not been described. METHODS: We retrospectively investigated 119 de novo living donor kidney transplant patients treated with Tac-QD (n = 90) or Tac-BID (n = 29) and their 3- and 12-month PB results. Other immunosuppressive drugs administered included basiliximab, mycophenolate mofetil, and methylprednisolone. We evaluated daily doses and trough levels of Tac and serum creatinine levels, and compared pathologic findings. RESULTS: Daily doses were higher in the Tac-QD group, but trough levels and serum creatinine levels were comparable. On 3- and 12-month PB, the frequency of subclinical rejection was similar between the groups, whereas interstitial fibrosis and tubular atrophy (IF/TA) were less common in the Tac-QD group at 12 months (42.2% vs 20.6%, P = .04). Univariate and multivariate logistic regression analyses revealed that allograft rejection (borderline changes or higher) was associated with IF/TA (odds ratio 4.09, 95% confidence interval 1.76-10.10, P = .001). The Tac-QD-based regimen showed a trend toward the absence of IF/TA but it did not reach statistical significance. Tubular vacuolization and arteriolar hyaline changes were also comparable in the two groups. CONCLUSIONS: We found a trend toward milder IF/TA, but no significant differences in kidney allograft pathology in patients who were administered Tac-QD- versus Tac-BID-based regimens at 12 months. The effects of Tac-QD on chronic allograft injury must be studied by longer observation.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Doadores Vivos , Tacrolimo/administração & dosagem , Adulto , Biópsia , Protocolos Clínicos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Transplant Proc ; 46(2): 560-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24656012

RESUMO

BACKGROUND: Polyomavirus BK nephropathy (BKVN) is an important infectious complication in kidney transplant patients. Regular screening using polymerase chain reaction for BK virus DNA in plasma and urinary cytology is effective for early diagnosis of BKVN. However, methods of follow-up and therapeutic targets are not well described. METHODS: Ten patients with BKVN who received biweekly urinary cytology and repeat biopsies after diagnosis were retrospectively studied. Histological remission of BKVN was determined when biopsy revealed negative SV40 large T-antigen (TAg) staining. Results of urinary cytology and repeat biopsy findings were compared. RESULTS: Urinary decoy cells disappeared in 8 of 10 patients 55 ± 25 (range 13-79) days after index biopsies. In those cases, allograft function was preserved and the final serum creatinine level was 2.14 ± 1.19 (0.80-4.55) mg/dL after 962 ± 393 (325-1563) days of follow-up. Two cases with persistent urinary decoy cells shedding lost their graft 195 and 362 days later. Amongst 29 repeat biopsies, there were 13 TAg-positive and 16 negative biopsies. In 12 of 13 TAg-positive biopsies (92%), urinary decoy cells were still positive, whereas at the same time in 15 TAg-negative biopsies, decoy cells had already disappeared (94%). CONCLUSIONS: Cytology testing is advantageous because of its cost effectiveness. Clearance of decoy cells from urine was closely related to histological remission of BKVN, and may possibly be a therapeutic target in BKVN.


Assuntos
Vírus BK/fisiologia , Nefropatias/virologia , Urina/virologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Transplant Proc ; 45(8): 2903-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24157001

RESUMO

BACKGROUND: Various studies have reported poorer graft survival among individuals displaying T-cell-positive flow cytometry crossmatches (FCXM). Good outcomes have been observed in immunologically high-risk patients with the use of rituximab, plasmapheresis, and γ-globulin. Because the relevance of FCXM B-cell-positivity (BCXM (+)) alone remains controversial, we examined its impact on living donor renal transplantations. PATIENTS AND METHODS: We retrospectively studied 146 adult renal transplantation recipients from April 2007 to June 2012, dividing the patients into BCXM (+) (n = 31) versus BCXM (-) recipients (n = 115). We examined patient and graft survivals as well as rejection rates at 0 to 3, 3 to 12, and 12 to 24 months. We also determined the incidence of infectious diseases. We performed stepwise multivariate regression to identify risk factors contributing rejection episodes. RESULTS: One-year patient and graft survivals were 100% in both groups. The BCXM (-) group have a 16.8% rejection probability whereas the BCXM (+) group, 33.2% (P = .201). There were no significantly differences in the incidence of infectious diseases. Only the rate of a sensitizing history was an independent risk factor for a rejection episode. CONCLUSION: BCXM (+) showed only a tendency but not a significant impact on rejection episodes compared with BCXM (-); short-term graft survivals were similar.


Assuntos
Linfócitos B/imunologia , Citometria de Fluxo/métodos , Teste de Histocompatibilidade , Transplante de Rim , Doadores Vivos , Adulto , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Transplant Proc ; 45(6): 2469-75, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23953564

RESUMO

The outcomes of organ transplantation have improved due to better immunosuppressive drugs, surgical techniques, and management of complications. However, ischemia-reperfusion injury remains a challenge affecting graft survival. In this study, we employed injection of a protein transduction domain (PTD) to inhibit the c-Jun NH2-terminal kinase (JNK) pathway thereby attenuating ischemia-reperfusion injury in a porcine model. The PTD-JNK inhibitor (JNKI) was administered into the renal artery, allowing it to be taken into various elements including vascular endothelial cells by endocytosis via the PTD. Serum creatinine and blood urea nitrogen concentrations were lower among PTD-JNKI than controls. In addition, renal tissue blood flow was maintained in the PTD-JNKI group, resulting in less tissue injury and fewer apoptotic cells. These results suggested that the PTD technique improved renal transplantation outcomes.


Assuntos
Peptídeos Penetradores de Células/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Permeabilidade da Membrana Celular , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/metabolismo , Isquemia Fria/efeitos adversos , Creatinina/sangue , Citoproteção , Modelos Animais de Doenças , Endocitose , Feminino , Injeções Intra-Arteriais , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Rim/irrigação sanguínea , Rim/enzimologia , Rim/patologia , Nefropatias/enzimologia , Nefropatias/etiologia , Nefropatias/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/metabolismo , Artéria Renal , Circulação Renal/efeitos dos fármacos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Suínos , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Resistência Vascular/efeitos dos fármacos
7.
Transplant Proc ; 43(5): 1489-94, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21693223

RESUMO

BACKGROUND: Milrinone (MIL), a phosphodiesterase (PDE) 3 inhibitor, exhibits cardiotonic and angioectatic effects. Various PDE inhibitors have been shown to suppress inflammatory cytokines. In this study, we evaluated the angioectatic and anti-inflammatory cytokine effects of MIL on renal function after warm ischemia in a rat ischemia-reperfusion (I-R) injury model. MATERIALS AND METHODS: MIL or control solution was perfused from the left renal artery to the right kidney, and the left kidney was excised. The right renal artery, vein, and ureter were clamped and then released after 50 minutes to produce warm ischemia. We evaluated control (n = 7), MIL (n = 7), and sham operation (n = 7) groups for serum creatinine, blood urea nitrogen (BUN), blood flow, expression of tumor necrosis factor (TNF)-α mRNA, apoptosis index, and histological evidence of acute tubular necrosis. RESULTS: Serum creatinine and BUN concentrations peaked at 24 hours after reperfusion. MIL treatment significantly reduced serum creatinine (control group 1.27 ± 0.45 mg/dL vs MIL group 0.77 ± 0.19 mg/dL, P < .05; sham 0.35 ± 0.2 mg/dL) and BUN (control 67.6 ± 13.6 mg/dL vs MIL 51.0 ± 8.8 mg/dL, P < .05; sham 23.0 ± 4.2 mg/dL) levels at 24 hours. Thereafter, serum creatinine and BUN concentrations in the MIL group remained significantly lower compared with the control group for 120 hours (P < .05). MIL group exhibited significantly higher tissue blood flow, less acute tubular necrosis, lower expression of TNF-α mRNA in renal tissue, and lower apoptotic index (P < .05). CONCLUSIONS: MIL maintained renal tissue blood flow by its vasodilatory effect, suppressed expression of TNF-α mRNA by increasing intracellular cyclic adenosine monophosphate, and ultimately decreased tubular cell apoptosis, thus protecting renal function after warm I-R injury.


Assuntos
Rim/efeitos dos fármacos , Milrinona/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Sequência de Bases , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Primers do DNA , Rim/irrigação sanguínea , Ratos
8.
Transplant Proc ; 42(7): 2427-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20832520

RESUMO

OBJECTIVE: Kidney grafts with multiple renal arteries (MRAs) are not uncommon, but they do make transplantation more difficult. Laparoscopic graft nephrectomy has become the standard; however, the safety and reliability must be maintained for both a donor and a recipient even in case of MRAs. This study evaluated the short-term outcomes of living donor renal transplant using grafts with MRAs procured by laparoscopic nephrectomy. PATIENTS AND METHODS: This study reviewed all living donor kidney transplantations performed from January 2008 to June 2009, which were divided into 3 groups according to the number of renal graft arteries. The serum creatinine level, warm ischemic time (WIT), rewarming time, total ischemic time (TIT), operative time, acute rejection episodes, and complications in each group were evaluated. RESULTS: The serum creatinine level showed no difference among the groups. Longer TIT was observed in the MRAs group, but WIT and rewarming time did not differ. The acute rejection rate was not different. There were no vessel complications in any donors and recipients. CONCLUSION: Harvesting kidney grafts with MRAs by laparoscopic nephrectomy requires a longer TIT; however, transplantation can be performed safely and reliably for both donors and recipients.


Assuntos
Transplante de Rim/métodos , Laparoscopia/métodos , Doadores Vivos , Nefrectomia/métodos , Artéria Renal/cirurgia , Adolescente , Adulto , Idoso , Anastomose Cirúrgica/métodos , Criança , Pré-Escolar , Creatinina/sangue , Rejeição de Enxerto/epidemiologia , Humanos , Artéria Ilíaca/cirurgia , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Laparoscopia/normas , Pessoa de Meia-Idade , Nefrectomia/normas , Estudos Retrospectivos , Segurança , Coleta de Tecidos e Órgãos/métodos
9.
Transplant Proc ; 42(5): 1819-21, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20620530

RESUMO

The serious shortage of brain-dead donors leads to the use of pancreata from marginal donors, including cardiac death in Japan. We studied the islet histology of pancreas graft biopsies to investigate the adequacy of using pancreata from marginal donors. Pancreas allograft biopsy was performed originally to diagnose acute rejection (Drachenberg grade I-III) at a mean of 6 months after transplantation. The percentage of beta cells showing oxidative DNA changes, replication, and apoptosis was investigated in 7 recipients of simultaneous pancreas-kidney transplantations with good graft function from marginal donors. Their causes of death were cerebrovascular with donor ages >44 years (n = 3), cardiac (n = 2), and cerebrovascular (n = 2). The percentage of beta cells per islet in the transplanted pancreas (71.9 +/- 3.3%) did not correlate with glycemic control or insulin secretion, but did correlated inversely with donor age (r = -0.81; P < .05). Oxidative DNA changes as revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present in islet cells as well as in the exocrine cells of the transplanted pancreas. The percentage of 8-OHdG-positive cells per pancreas (71.8 +/- 4.5%) did not correlate with glycemic levels, insulin secretion, donor age, or ischemic time. There were no Ki67-positive replicating cells or terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive apoptotic islet cells. Transplanted pancreata from marginal donors showed preserved beta cells and function despite diffuse oxidative changes.


Assuntos
Transplante das Ilhotas Pancreáticas/patologia , Doadores de Tecidos/estatística & dados numéricos , Adulto , Fatores Etários , Glicemia/metabolismo , Cadáver , Causas de Morte , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Ilhotas Pancreáticas/citologia , Transplante das Ilhotas Pancreáticas/mortalidade , Japão , Masculino , Pessoa de Meia-Idade
10.
Diabetologia ; 53(2): 341-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19911164

RESUMO

AIMS/HYPOTHESIS: A 41-year-old woman undergoing simultaneous pancreas-kidney transplantation from an HLA-mismatched cardiac death donor abruptly developed overt hyperglycaemia under standard immunosuppressive therapy at 48 months after transplantation. Unexpectedly, we found insulitis in the transplanted pancreas and characterised the insulitis. METHODS: Pancreas graft biopsies were performed 3 years before and after the development of hyperglycaemia and the specimens were examined histologically. RESULTS: Insulitis was absent in the first biopsy, although oxidative DNA changes revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present both in islet cells and exocrine cells. No Ki67-positive proliferating cells were seen in the islets. Anti-glutamic acid decarboxylase antibody was undetectable 6 months earlier but increased to 6.3 U/l at the development of hyperglycaemia. The level of anti-insulinoma-associated protein 2 antibody was 18.5 U/l. Insulin secretion was severely suppressed and insulin therapy was resumed. In the second biopsy, although acute allograft rejection was minimal, insulin-positive beta cells were markedly reduced, and glucagon-positive alpha cells predominated. CD3-positive T lymphocytes, CD8-positive cytotoxic T lymphocytes and CD68-positive macrophages infiltrated around and into islets. The infiltrating cells expressed Fas ligand as well as granzyme B. More than 80% of islets were affected by insulitis. 8-OHdG-positive cells were also present in islets and exocrine tissue. The percentage of Ki67-positive cells in total islet cells was 1.5%. There were no TUNEL-positive apoptotic cells in the islet cells. CONCLUSIONS/INTERPRETATION: The histological features of insulitis in transplanted pancreas were consistent with common type 1 diabetes mellitus, but the clinical course of the recurrence appeared to be more rapid.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Hiperglicemia/diagnóstico , Transplante de Rim/patologia , Transplante de Pâncreas/patologia , Transplante de Pâncreas/fisiologia , Adulto , Biópsia , Cadáver , Nefropatias Diabéticas/cirurgia , Nefropatias Diabéticas/terapia , Feminino , Glucagon/análise , Rejeição de Enxerto/patologia , Humanos , Hiperinsulinismo/patologia , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Insulina/uso terapêutico , Secreção de Insulina , Complicações Pós-Operatórias/diagnóstico , Recidiva , Diálise Renal , Doadores de Tecidos , Adulto Jovem
11.
Transplant Proc ; 41(10): 4274-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20005383

RESUMO

OBJECTIVE: The aim of this study was to evaluate the availability of a pancreatic allograft biopsy via a laparotpmy. PATIENTS AND METHODS: From September 2004 to November 2007, 17 pancreas transplantations were performed: 15 simultaneous pancreas and kidney transplantations (SPK), 1 pancreas transplant alone (PTA), and one pancreas after kidney transplantation (PAK). Thirteen pancreatic allograft biopsies were obtained via an open laparotomy. This study evaluated the complications associated with this procedure, the rate of obtaining an adequate sample, and the relationship between biopsy-proven rejections and laboratory markers. In SPK cases we evaluated the synchronization between pancreas and kidney rejection. The pancreatic samples were diagnosed according to the Drachenberg classification. RESULTS: No complications resulted from the procedure. The rate of obtaining adequate samples was 84.6%. Pancreas rejection correlated with elevation of the laboratory markers in 71.4%. Simultaneous pancreas and kidney rejection occurred in 62.5%, only kidney in 25%, and only pancreas in 12.5%. CONCLUSION: A pancreas graft biopsy was absolutely imperative to improve the outcome in PTA, and even in SPK cases. A pancreatic allograft biopsy via a laparotomy was a safe, necessary and easy procedure to obtain an accurate diagnosis of rejection among pancreas transplantation patients.


Assuntos
Biópsia/métodos , Transplante de Pâncreas/patologia , Rejeição de Enxerto/patologia , Humanos , Transplante de Rim/imunologia , Transplante de Rim/patologia , Laparotomia/métodos , Cavidade Peritoneal/diagnóstico por imagem , Cavidade Peritoneal/patologia , Estudos Retrospectivos , Transplante Homólogo/patologia , Ultrassonografia
12.
Phytomedicine ; 9(6): 536-45, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12403163

RESUMO

Components of Agaricus blazei Murill have been demonstrated to have a wide range of immunopotentiating activities. The present study was designed to evaluate the effect of A. blazei Murill upon activation of the complement system in human serum in vitro. Additional studies were performed to determine the cytotoxic effect of complement-opsonized particles of A. blazei Murill against human tumor cells in culture. A fine particle of A. blazei Murill (ABP), prepared by mechanical disruption, was used throughout the experiments. ABP activated the human complement system via the alternative pathway in human serum. Activation of the alternative pathway was both time- and dose-dependent. When the particles from fruiting bodies of A. blazei Murill (ABP-F) were reacted with human serum, the formation of complement-opsonized ABP, iC3b-ABP-F complexes, and binding of the complexes to human peripheral blood monocytes, were demonstrated in vitro by immunofluorescence. Further, the resident human peripheral nucleated cells incubated in the presence of iC3b-ABP-F complexes inhibited the proliferation of human tumor cell line TPC-1 in vitro.


Assuntos
Agaricus , Via Alternativa do Complemento/efeitos dos fármacos , Adulto , Complemento C3b/metabolismo , Testes Imunológicos de Citotoxicidade , Sulfato de Dextrana/farmacologia , Relação Dose-Resposta a Droga , Imunofluorescência , Estruturas Fúngicas/química , Humanos , Soros Imunes/metabolismo , Imunoeletroforese , Masculino , Monócitos/efeitos dos fármacos , Fagocitose , Ligação Proteica/efeitos dos fármacos , Fatores de Tempo , Células Tumorais Cultivadas
13.
Surgery ; 129(3): 309-17, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11231459

RESUMO

BACKGROUND: The role of inflammatory cytokines is still unclear in ischemia-reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR), a newly developed compound that is a potent suppressor of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs. METHODS: The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of the pancreas was removed. A control group (n = 14) and an FR treatment group (n = 11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes, creatinine, IL-1beta mRNA in the peripheral blood, and histopathology. RESULTS: Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041) than did the control group, but there was no remarkable change in endocrine function (P =.422). Pao(2) during the acute phase in the FR treatment group was maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liver and kidneys were unremarkable. CONCLUSIONS: FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may contribute to secondary damage to distant organs.


Assuntos
Isquemia/patologia , Isquemia/fisiopatologia , Pâncreas/irrigação sanguínea , Pirazóis/farmacologia , Piridinas/farmacologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Animais , Cães , Feminino , Interleucina-1/sangue , Ilhotas Pancreáticas/fisiopatologia , Masculino , Pâncreas/fisiopatologia
14.
Int J Oral Maxillofac Surg ; 29(4): 280-4, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11030400

RESUMO

Three-phase bone scintigraphy was undertaken to check the anastomotic patency and monitor the viability of vascularized bone grafts. Ten consecutive patients who underwent vascularized bone grafting of the mandible were reviewed. A successful clinical outcome was achieved in 8 patients. The graft failed in 2 patients. In this series, 3-phase bone scintigraphy of radiolabeled (99m)Tc-methylene-diphosphonate was performed at 7 days, and at 1, 3, 6, and 12 months after reconstruction. Assessments made using 3-phase bone images were compared with the clinical findings. The clinical outcome of the cases presented in our series correlated extremely well with 3-phase bone images. Three-phase bone scintigraphy is a useful method for the assessment of patency and viability of vascularized bone grafts. The use of this method can be very helpful in assessing the anastomotic patency and viability of a graft which for clinical reasons is suspected of being non-viable.


Assuntos
Transplante Ósseo/diagnóstico por imagem , Mandíbula/cirurgia , Idoso , Anastomose Cirúrgica , Transplante Ósseo/fisiologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Doenças Mandibulares/cirurgia , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Osteorradionecrose/cirurgia , Cintilografia , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99m , Grau de Desobstrução Vascular
15.
Carcinogenesis ; 21(2): 251-6, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10657965

RESUMO

The effects of antibiotics and anti-inflammatory drugs on the promotion stage of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol. In experiment 1, rats received tap water containing 2000 p.p.m. BHP for 12 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0. 04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration. The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to. Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed. In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon. Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP. The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics.


Assuntos
Adenocarcinoma/prevenção & controle , Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Carcinógenos/toxicidade , Carcinoma Adenoescamoso/prevenção & controle , Carcinoma de Células Escamosas/prevenção & controle , Cocarcinogênese , Medicamentos de Ervas Chinesas/administração & dosagem , Eritromicina/administração & dosagem , Neoplasias Pulmonares/prevenção & controle , Nitrosaminas/toxicidade , Penicilinas/administração & dosagem , Piroxicam/administração & dosagem , Pneumonia Bacteriana/tratamento farmacológico , Adenocarcinoma/induzido quimicamente , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Carcinoma Adenoescamoso/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Eritromicina/farmacologia , Eritromicina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação , Neoplasias Pulmonares/induzido quimicamente , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Penicilinas/farmacologia , Penicilinas/uso terapêutico , Piroxicam/farmacologia , Piroxicam/uso terapêutico , Extratos Vegetais , Pneumonia Bacteriana/complicações , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis , Organismos Livres de Patógenos Específicos
17.
Biochem Biophys Res Commun ; 250(2): 246-51, 1998 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-9753615

RESUMO

Xenopus laevis oocytes were used as a gene expression system to characterize the carrier-mediated transport of valacyclovir (vacv), the L-valine ester prodrug of the acyclic nucleoside acyclovir (acv). A significant increase in the uptake of [3H]vacv by Xenopus laevis oocytes injected with human intestinal peptide transporter (hPepT1) cRNA compared to the uptake by water injected oocytes indicated that vacv was translocated by hPepT1. Vacv uptake was found to be concentration dependent, saturable (K(m) = 5.94 +/- 1.91 mM and Jmax = 1.68 +/- 0.25 nmoles/hr/oocyte), pH dependent, and inhibited by various known substrates of hPepT1 but not by acv, valine or pentaglycine. Vacv also inhibited the uptake of 14C-glycylsarcosine, a known substrate of hPepT1, in a concentration-dependent manner (Ki = 4.08 +/- 1.02 mM). These results demonstrate that human intestinal peptide transporter hPepT1 has broad specificity since it recognizes vacv as a substrate even though it lacks a typical peptide bond.


Assuntos
Aciclovir/análogos & derivados , Proteínas de Transporte/metabolismo , Pró-Fármacos/metabolismo , Simportadores , Valina/análogos & derivados , Aciclovir/metabolismo , Animais , Transporte Biológico , Proteínas de Transporte/genética , Feminino , Expressão Gênica , Humanos , Oócitos , Transportador 1 de Peptídeos , RNA Complementar/genética , Valaciclovir , Valina/metabolismo , Xenopus laevis
18.
Gan To Kagaku Ryoho ; 25(9): 1318-21, 1998 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-9703817

RESUMO

Nine cases of advanced uterine body cancer (stage III: 8, stage IVa: 1) were treated by intra-arterial infusion chemotherapy before curative operation. This treatment produced primary tumors smaller than half sizes in eight cases. Necrotic changes were found in over two-thirds of the lesions in six cases. This chemotherapy enabled us to operate curatively in seven cases. After the operations, we performed various types of treatment including intra-arterial infusion chemotherapy. No evidences of disease have been found in four cases, but there is no significant difference between the groups receiving and not receiving the intra-arterial infusion chemotherapy (n = 16) in terms of survival rate of stage III. Further study of the prognosis is necessary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Cuidados Pré-Operatórios , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Epirubicina/administração & dosagem , Feminino , Humanos , Histerectomia , Infusões Intra-Arteriais , Excisão de Linfonodo , Pessoa de Meia-Idade , Mitomicina/administração & dosagem
19.
Int J Pancreatol ; 21(3): 253-7, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9322125

RESUMO

CONCLUSION: We have described a case of pancreatic tumor formed by adult T-cell leukemia (ATL) cell infiltration. BACKGROUND: The patient was diagnosed as chronic ATL hematologically with the findings of increased number of atypical lymphocytes, ATL cells in the peripheral blood, and positive human T-cell leukemia virus type I (HTLV-I) antibody in the serum. The pancreatic tumor was identified by ultrasonography and computed tomography as a diffusely swollen tumor from the body to the tail of the pancreas. Biopsy specimen confirmed the ATL cell infiltration into the pancreas immunohistochemically, and Southern blot analysis showed the integration of HTLV-I proviral DNA both in the pancreas and in the peripheral blood. RESULTS: The pancreatic tumor diminished spontaneously without chemotherapy when ATL cells in the peripheral blood disappeared by spontaneous regression.


Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Infiltração Leucêmica , Neoplasias Pancreáticas/patologia , Idoso , Divisão Celular/fisiologia , Humanos , Masculino
20.
Surg Today ; 27(3): 238-42, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9068105

RESUMO

The case of a 70-year-old Japanese woman with adenoid cystic carcinoma (ACC) of the esophagus is presented herein. The patient presented with progressive dysphagia, and an upper gastrointestinal series and esophagogastroscopy revealed a protruding tumor located in the middle portion of the esophagus. Ultrasonography (US) and computed tomography (CT) suggested a lymph node metastasis between the left lobe of the liver and the esophagocardiac junction. Histopathologic examination of a biopsy specimen showed squamous cell carcinoma (SCC) and a subtotal esophagectomy was performed under the preoperative diagnosis of esophageal carcinoma. However, the histopathologic diagnosis of the resected specimen proved to be ACC of the esophagus with a lymph node metastasis around the left gastric artery. We report the clinicopathological findings of this case and briefly discuss the clinical implications of ACC.


Assuntos
Carcinoma Adenoide Cístico/patologia , Neoplasias Esofágicas/patologia , Linfonodos/patologia , Idoso , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/ultraestrutura , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/ultraestrutura , Feminino , Humanos , Metástase Linfática , Toracotomia
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