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1.
Nihon Geka Gakkai Zasshi ; 113(5): 451-5, 2012 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-23061368

RESUMEN

Beta cell replacement by islet transplantation is a promising clinical therapy for patients with type 1 diabetes because it satisfies safety issues and offers reliability in controlling blood glucose levels. One remaining problem is that it requires islets from two to three donor pancreases to achieve insulin independence, thus aggravating the donor shortage. Islet regeneration in vivo and generation of beta cells ex vivo followed by transplantation represent attractive therapeutic methods to restore the beta cell mass. Recent studies have suggested a number of postnatal pancreatic epithelial cells as candidate sources for future beta cell replacement therapy. Beta cells can reenter the cell cycle after a brief quiescent stage, suggesting the potential for engineering for expansion. The mechanisms of alpha cell-to-beta cell transdifferentiation can also be utilized to increase the beta cell population. Pancreatic ductal cells can proliferate and differentiate into regenerated beta cells. Pancreatic acinar cells are also observed to transdifferentiate into endocrinal cells, although infrequently under in vivo conditions. After a few more series of careful studies performed on human cells, the ultimate goal of translation to the clinic appears to be just around the corner. Islet cell transplantation will become a welcome new form of cell-regeneration therapy.


Asunto(s)
Ingeniería Celular/métodos , Diabetes Mellitus Tipo 1/terapia , Células Secretoras de Insulina/trasplante , Animales , Humanos
2.
Cell Transplant ; 21(2-3): 509-16, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22793059

RESUMEN

For islet transplantation, maintaining organ viability after pancreas procurement is critically important for optimal graft function and survival. We recently reported that islet yield was significantly higher in the modified ET-Kyoto (MK) solution, which includes a trypsin inhibitor (ulinastatin), compared with the UW solution, and that the advantages of MK solution are trypsin inhibition and less collagenase inhibition. In this study, we compared ulinastatin with other trypsin inhibitors, gabexate mesilate, and nafamostat mesilate, in preservation solution for islet isolation. Ulinastatin was easily dissolved in ET-Kyoto solution, while ET-Kyoto with gabexate mesilate and nafamostat mesilate became cloudy immediately after addition. Although there were no significant differences in islet yield among the three groups, viability was significantly higher for the MK group than for the GK group or the NK group. The stimulation index was significantly higher for the MK group than for the GK group. In summary, there are no other trypsin inhibitors that are more effective than ulinastatin. Based on these data, we now use ET-Kyoto solution with ulinastatin for clinical islet transplantation.


Asunto(s)
Separación Celular/métodos , Gabexato/farmacología , Glicoproteínas/farmacología , Guanidinas/farmacología , Islotes Pancreáticos/citología , Animales , Benzamidinas , Supervivencia Celular/efectos de los fármacos , Gabexato/química , Gluconatos/química , Glicoproteínas/química , Guanidinas/química , Derivados de Hidroxietil Almidón/química , Islotes Pancreáticos/efectos de los fármacos , Fosfatos/química , Porcinos , Trehalosa/química , Tripsina/metabolismo , Inhibidores de Tripsina/farmacología
3.
Cell Transplant ; 21(5): 909-18, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22330060

RESUMEN

Since donor T-cells' allorecognition of host antigens is a prerequisite for the onset of graft-versus-host disease (GVHD), blocking their cellular signaling pathways can decrease the severity of GVHD. We hypothesized that epigallocatechin-3-gallate (EGCG), due to its strong affinity to macromolecules, would adhere to surface molecules of donor T cells, inhibit their allorecognition, and attenuate GVHD in the recipient. We tested the hypothesis by treating donor splenocytes with EGCG in both in vitro and in vivo murine GVHD models. EGCG treatment decreased the proliferation of donor cells in MLR cultures and secretion of IL-2 and INF-γ. It also reduced the epitope detection of CD3ɛ, CD4, and CD28 but did not downregulate the protein expression of these molecules, suggesting blockage of cell surface stimulatory signals. Similarly, EGCG treatment did not decrease mRNA expression for some of these molecules but decreased mitogen-induced cell proliferation, indicating that EGCG did not interfere the transcription of these genes but affected cell proliferation pathways. Furthermore, EGCG-treated donor splenocytes, when transplanted into immunocompromized recipient mice, decreased of proliferation, and the treatment extended the recipients' survival at least during the early stage of GVHD. These results strongly suggest that EGCG attenuates GVHD by both blocking specific cell surface molecules and affecting the donor T-cell proliferation pathways.


Asunto(s)
Enfermedad Injerto contra Huésped/tratamiento farmacológico , Polifenoles/uso terapéutico , Té/química , Animales , Antígenos CD28/inmunología , Antígenos CD28/metabolismo , Complejo CD3/inmunología , Complejo CD3/metabolismo , Antígenos CD4/inmunología , Antígenos CD4/metabolismo , Catequina/análogos & derivados , Catequina/farmacología , Catequina/uso terapéutico , Proliferación Celular/efectos de los fármacos , Femenino , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Huésped Inmunocomprometido , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mitógenos/farmacología , Polifenoles/farmacología , Bazo/citología , Bazo/trasplante
4.
Clin J Gastroenterol ; 4(3): 174-178, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26189350

RESUMEN

Extrahepatic bile duct cancer with an endocrine cell component has rarely been reported. We report here on a case of adenoendocrine cell carcinoma in the middle bile duct. An 82-year-old man was admitted to hospital for jaundice and anorexia. Computed tomography and magnetic resonance imaging examination showed a papillary low-density mass in the middle bile duct. Endoscopic retrograde cholangiography showed obstruction of the bile duct, and blushing cytology of the bile duct revealed an adenocarcinoma. We resected the extrahepatic bile duct with regional lymph node dissection. A pathological examination revealed a neuroendocrine component showing small cytoplasmic cells with hyperchromatic nuclei and a rosette-like structure in the middle of the tumor. In the peripheral mucosal region, there was a well-differentiated adenocarcinoma composed of columnar and cuboidal epithelial cells with clear and slightly granular eosinophilic cytoplasm. Immunohistochemical analysis showed positive staining for CD56, following the diagnosis of adenoendocrine cell carcinoma. The Ki-67 rate was >30% suggesting a small-cell endocrine carcinoma. The adenocarcinoma component infiltrated into the endocrine component, and some of the endocrine component was positive for cytokeratin, suggesting transdifferentiation of the adenocarcinoma into the endocrine component rather than originating from the common precursor cell. The patient experienced liver metastasis 3 months after the operation and died 6 months after the operation. Adenoendocrine tumor of the bile duct is extremely rare and adjuvant chemotherapy is necessary according to the malignant potential of the neuroendocrine tumor rather than the adenocarcinoma.

5.
Int J Clin Oncol ; 15(3): 294-300, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20232101

RESUMEN

BACKGROUND: Para-aortic lymph node (PALN) metastasis is an important prognostic factor in patients with pancreatic cancer, but accurate preoperative diagnosis is difficult. The objective of this study was to assess the accuracy of diagnosis of PALN by computed tomography (CT), magnetic resonance imaging (MRI), and (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET). METHODS: From August 2005 to July 2008, 119 patients with invasive ductal adenocarcinoma of the pancreas were included in this study. PALNs with a longer diameter >10 mm on CT or MRI were suspected of being involved by metastasis, whereas FDG uptake exceeding that of the adjacent normal tissue was considered to be positive for metastasis on FDG-PET studies. The imaging findings were compared with the pathological diagnosis of PALN metastasis. RESULTS: PALN dissection was performed in 71 patients (60.0%). Although histopathological examination revealed metastasis in 6 patients (8.5%), none of these patients was positive in any of the preoperative imaging studies. The longer diameter, the shorter diameter, the ratio of the two diameters, and the calculated lymph node volume showed no significant differences between patients with and without PALN metastasis. CONCLUSIONS: Preoperative detection of PALN metastasis in patients with pancreatic cancer is very difficult. Intraoperative histopathological examination of frozen sections is necessary if radical resection is contemplated.


Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico , Fluorodesoxiglucosa F18 , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética , Neoplasias Pancreáticas/diagnóstico , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/secundario , Carcinoma Ductal Pancreático/cirugía , Distribución de Chi-Cuadrado , Femenino , Humanos , Japón , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pancreatectomía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Cuidados Preoperatorios
6.
Cell Transplant ; 18(5): 541-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19775515

RESUMEN

Islet transplantation has recently emerged as an effective therapy and potential cure for type 1 diabetes mellitus. Recent reports show that the two-layer method (TLM), which employs oxygenated perfluorochemical (PFC) and University of Wisconsin (UW) solution, is superior to simple cold storage in UW for pancreas preservation in islet transplantation. Moreover, we recently reported that islet yield was significantly higher in the ET-Kyoto solution with ulinastatin (MK)/PFC preservation solution compared with the UW/PFC preservation solution in the porcine model and that the advantages of MK solution are trypsin inhibition and less collagenase inhibition. In this study, we compared ulinastatin with another trypsin inhibitor, Pefabloc, in preservation solution for islet isolation. Islet yield before purification was higher in the MK/PFC group compared with the ET-Kyoto with Pefabloc (PK)/PFC group. The stimulation index was higher for the MK/PFC group than for the PK/PFC group. These data suggest that ET-Kyoto with ulinastatin was the better combination for pancreas preservation than ET-Kyoto with Pefabloc. Based on these data, we now use ET-Kyoto solution with ulinastatin for clinical islet transplantation.


Asunto(s)
Islotes Pancreáticos/citología , Preservación de Órganos/métodos , Inhibidores de Tripsina/farmacología , Adenosina/farmacología , Alopurinol/farmacología , Animales , Separación Celular , Diabetes Mellitus Tipo 1/terapia , Fluorocarburos/farmacología , Gluconatos/farmacología , Glutatión/farmacología , Glicoproteínas/farmacología , Derivados de Hidroxietil Almidón/farmacología , Insulina/farmacología , Trasplante de Islotes Pancreáticos , Soluciones Preservantes de Órganos/farmacología , Fosfatos/farmacología , Rafinosa/farmacología , Sulfonas/farmacología , Porcinos , Trehalosa/farmacología
8.
Drug Metab Pharmacokinet ; 24(2): 175-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19430174

RESUMEN

We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Both patients were administered tacrolimus with sirolimus or everolimus. They had been administered 5 or 9 mg sirolimus once a day and had maintained a trough concentration of about 15 ng/mL as measured by high performance liquid chromatography with ultraviolet detection. After the switch from sirolimus to everolimus, they were given 10 or 12 mg/day of everolimus twice a day to maintain a trough concentration of 12-15 ng/mL as measured by a fluorescence polarization immunoassay (FPIA) method. Afterward, the blood concentrations of everolimus and sirolimus after the conversion were measured by high performance liquid chromatography with mass spectrometry and everolimus concentrations were found to be 5-10 ng/mL. These data show that a larger dosage is needed for everolimus than sirolimus to maintain the same trough blood concentration. Data obtained by the FPIA for everolimus should be carefully evaluated after switching from sirolimus to everolimus because of the cross-reactivity of the antibody with sirolimus.


Asunto(s)
Trasplante de Islotes Pancreáticos , Trasplante de Riñón , Sirolimus/análogos & derivados , Sirolimus/sangre , Tacrolimus/sangre , Adulto , Cromatografía Líquida de Alta Presión/métodos , Monitoreo de Drogas , Everolimus , Femenino , Inmunoensayo de Polarización Fluorescente/métodos , Humanos , Inmunosupresores , Islotes Pancreáticos , Espectrometría de Masas/métodos , Persona de Mediana Edad , Distribución Tisular
9.
Hum Gene Ther ; 20(1): 73-85, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18925829

RESUMEN

Human islet isolation to obtain high-quality islets is still challenging. This study investigates how c-Jun NH2- terminal kinase (JNK ) is activated during human and porcine islet isolation. We also investigated whether ductal injection of preservation solution with JNK inhibitors improves islet isolation results by preventing apoptosis of islet cells. A low molecular weight inhibitor (SP600125) and a cell-permeable peptide inhibitor, the latter introduced by protein transduction technology, were used in porcine and human studies, respectively. JNK activity progressively increased during the isolation procedure. The addition of 10 microM JNK inhibitors into the ductal preservation solution prevented JNK activation during the isolation procedure and prevented islet apoptosis immediately after isolation. We incubated islets (2000 islet equivalents) for 24-48 hr and then transplanted them below the kidney capsule of streptozotocin-induced diabetic mice. The blood glucose levels reached normoglycemia in more than 80% of the JNK inhibitor-positive group, whereas less than 20% of the JNK inhibitor-negative group achieved normoglycemia. These findings suggest that the JNK pathway is the major mediator of islet deterioration during/immediately after isolation and that JNK inhibition before islet isolation could improve outcomes after pancreatic islet transplantation.


Asunto(s)
Apoptosis , Inhibidores Enzimáticos/administración & dosificación , Supervivencia de Injerto , Islotes Pancreáticos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Soluciones Preservantes de Órganos/administración & dosificación , Páncreas/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/fisiología , Humanos , Islotes Pancreáticos/citología , Islotes Pancreáticos/efectos de los fármacos , Trasplante de Islotes Pancreáticos/fisiología , Ratones , Ratones Desnudos , Preservación de Órganos , Páncreas/citología , Páncreas/cirugía , Porcinos , Recolección de Tejidos y Órganos
10.
Cell Transplant ; 17(6): 649-56, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18819253

RESUMEN

Recently, we demonstrated that islet transplantation from non-heart-beating donors (NHBDs) using the Kyoto islet isolation method (KIIM) successfully reversed patients' diabetes state. In this study, we evaluated the effects of donor- and isolation-related variables on islet isolation results from NHBDs by KIIM. Twenty-one islet preparations from the pancreata of NHBDs were isolated by KIIM. Islet preparations that met transplantation criteria and achieved improved patient diabetes control after transplantation were defined as successful isolations. Potential risk factors deemed to affect islet isolation results, such as age, gender, body mass index, hospital stay, donors' blood biochemical tests, a modified pancreata procurement method, and isolation and purification procedure-related variables, were analyzed. Seventeen out of 21 islet isolations (81%) were successful isolations. Postpurification islet yield was 447,639 +/- 39,902 islet equivalents (IE) in the successful isolation group and 108,007 +/- 31,532 IE in the failure group. Donor age was significantly younger in the success group (41.9 +/- 4.0 years old in the success group vs. 57.5 +/- 2.2 years old in the failure group, p = 0.003). Chronic pancreatitis significantly decreased islet yields (p = 0.006). Phase I time was significantly shorter (p = 0.010) and undigested tissue volume was significantly smaller (p = 0.020) in the success group. Purity was in positive correlation to postpurification islet yield, while donor age was in reverse correlation to postpurification islet yield. KIIM enables us to perform islet transplantation from NHBDs; however, the decision to use pancreata from older donors or those with chronic pancreatitis requires careful consideration.


Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Trasplante de Islotes Pancreáticos/métodos , Recolección de Tejidos y Órganos/métodos , Adulto , Índice de Masa Corporal , Peso Corporal , Separación Celular/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Donantes de Tejidos
11.
Curr Opin Organ Transplant ; 13(2): 135-41, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18685293

RESUMEN

PURPOSE OF REVIEW: To summarize advances and limitations in pancreas procurement and preservation for pancreas and islet transplantation, and review advances in islet protection and preservation. RECENT FINDINGS: Pancreases procured after cardiac death, with in-situ regional organ cooling, have been successfully used for islet transplantation. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are comparable to University of Wisconsin solution when used for cold storage before pancreas transplantation. Colloid-free preservation solutions are inferior to University of Wisconsin solution for pancreas preservation prior to islet isolation and transplantation. Clinical reports on pancreas transplants suggest that the two-layer method may not offer significant benefits over cold storage with the University of Wisconsin solution: improved oxygenation may depend on the graft size; benefits in experimental models may not translate to human organs. Improvements in islet yield and quality occurred from pancreases treated with inhibitors of stress-induced apoptosis during procurement, storage, isolation or culture desirable before islet isolation and transplantation and may improve islet yield and quality. Methods for real-time, noninvasive assessment of pancreas quality during preservation have been implemented and objective islet-potency assays have been developed and validated. These innovations should contribute to objective evaluation and establishment of improved pancreas-preservation and islet-isolation strategies. SUMMARY: Cold storage may be adequate for preservation before pancreas transplants, but insufficient when pancreases are processed for islets or when expanded donors are used. Supplementation of cold-storage solutions with cytoprotective agents and perfusion may improve pancreas and islet transplant outcomes.


Asunto(s)
Trasplante de Islotes Pancreáticos , Preservación de Órganos , Trasplante de Páncreas , Páncreas , Humanos , Obtención de Tejidos y Órganos
12.
Curr Opin Organ Transplant ; 13(4): 445-51, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18685343

RESUMEN

PURPOSE OF REVIEW: To summarize advances and limitations in pancreas procurement and preservation for pancreas and islet transplantation, and review advances in islet protection and preservation. RECENT FINDINGS: Pancreases procured after cardiac death, with in-situ regional organ cooling, have been successfully used for islet transplantation. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are comparable to University of Wisconsin solution when used for cold storage before pancreas transplantation. Colloid-free preservation solutions are inferior to University of Wisconsin solution for pancreas preservation prior to islet isolation and transplantation. Clinical reports on pancreas and islet transplants suggest that the two-layer method may not offer significant benefits over cold storage with the University of Wisconsin solution: improved oxygenation may depend on the graft size; benefits in experimental models may not translate to human organs. Improvements in islet yield and quality occurred from pancreases treated with inhibitors of stress-induced apoptosis during procurement, storage, isolation or culture. Pancreas perfusion may be desirable before islet isolation and transplantation and may improve islet yields and quality. Methods for real-time, noninvasive assessment of pancreas quality during preservation have been implemented and objective islet potency assays have been developed and validated. These innovations should contribute to objective evaluation and establishment of improved pancreas preservation and islet isolation strategies. SUMMARY: Cold storage may be adequate for preservation before pancreas transplants, but insufficient when pancreases are processed for islets or when expanded donors are used. Supplementation of cold storage solutions with cytoprotective agents and perfusion may improve pancreas and islet transplant outcomes.

13.
Cell Transplant ; 17(1-2): 69-81, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18468237

RESUMEN

For islet transplantation, it is important to obtain an available islet mass adequate for diabetes reversal from a single donor pancreas. A recent report demonstrated that the use of M-Kyoto solution instead of UW solution improved islet yields in the two-layer method for pancreas preservation. The present study investigated whether the ductal injection of a large volume of preservation solution (UW and M-Kyoto solution) before pancreas storage improves islet yields. Islet yield both before and after purification was significantly higher in the ductal injection (+) group compared with the ductal injection (-) group. TUNEL-positive cells in the ductal injection (+) group were significantly decreased in comparison to the ductal injection (-) group. The ductal injection of preservation solution increased the ATP level in the pancreas tissue and reduced trypsin activity during the digestion step. Annexin V and PI assays showed that the ductal injection prevents islet apoptosis. In a transplant model, the ductal injection improved islet graft function. These findings suggest that the ductal injection of preservation solution, especially the M-Kyoto solution, leads to improved outcomes for pancreatic islet transplantation. Based on these data, this technique is now used for clinical islet transplantation from non-heart-beating donor pancreata or living donor pancreas.


Asunto(s)
Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos , Soluciones Preservantes de Órganos/administración & dosificación , Preservación de Órganos/métodos , Adenosina/administración & dosificación , Alopurinol/administración & dosificación , Animales , Separación Celular/métodos , Vías de Administración de Medicamentos , Glutatión/administración & dosificación , Supervivencia de Injerto , Insulina/administración & dosificación , Islotes Pancreáticos/anatomía & histología , Rafinosa/administración & dosificación , Porcinos , Trasplante Heterólogo
14.
Cell Transplant ; 17(1-2): 121-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18468242

RESUMEN

The evaluation of engraftment is important to assess the success of islet transplantation, but it is complex because islet transplantation usually requires two or more donors to achieve euglycemia. Islet transplantation from NHBDs was evaluated using new assessment forms for the secretory unit of islet in transplantation (SUIT) and engrafted islet rate (EIR) indexes. Insulin independence was obtained when the SUIT index was more than 28, which might indicate that 28% of the beta-cell mass of a normal subject is required for insulin independence. Because the average EIR for a single transplantation is about 30, the percentage of engrafted islets following one transplantation is about 30%, assuming that a normal subject has 1 million islet equivalents. Although few cultured islet transplants have been performed, the increase of the SUIT and EIR indexes in patients who received cultured islets was significantly lower than in patients who received fresh islets, suggesting that fresh islets may be more effective than cultured islets. The SUIT and EIR indexes are thus considered to be useful values for evaluating islet transplantation, especially for single islet transplantation.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Supervivencia de Injerto , Insulina/metabolismo , Trasplante de Islotes Pancreáticos , Animales , Glucemia/metabolismo , Muerte Encefálica , Cadáver , Humanos , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Islotes Pancreáticos/cirugía , Donantes de Tejidos
15.
Ann Clin Biochem ; 44(Pt 6): 570-2, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17961315

RESUMEN

We investigated a patient with type 1 diabetes mellitus undergoing pancreatic islets transplantation. In this patient, we evaluated the clinical usefulness of serial measurement of serum S100A8/A9 complex levels for detecting acute inflammatory responses associated with rejection of transplanted pancreatic islets. The serum S100A8/A9 complex was a more sensitive marker for acute inflammation associated with islet transplant rejection than the serum C-reactive protein. Thus, the serial measurement of the serum S100A8/A9 complex concentration is useful for monitoring the patients with pancreatic islet transplantation.


Asunto(s)
Calgranulina A/sangre , Calgranulina B/sangre , Diabetes Mellitus Tipo 1/terapia , Inflamación/diagnóstico , Inflamación/etiología , Trasplante de Islotes Pancreáticos/efectos adversos , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Glucemia/análisis , Proteína C-Reactiva/análisis , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico
16.
Transplantation ; 84(5): 655-8, 2007 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-17876281

RESUMEN

The use of University of Wisconsin (UW) preservation solution in islet transplantation has some disadvantages, including inhibition of collagenase activity for pancreatic digestion. Histidine-tryptophan-ketoglutarate (HTK) solution has demonstrated an efficacy similar to UW solution for organ preservation in clinical pancreas transplantation. Recently, we reported that islet yield from porcine pancreata was significantly gtreater when they were preserved using M-Kyoto solution compared with UW solution. Here, we compared HTK solution with ulinastatin (M-HTK) and M-Kyoto solution for islet yield. In porcine islet isolation, islet yield after purification was significantly greater in the M-Kyoto/perfluorochemical (PFC) group compared with the M-HTK/PFC group. The M-Kyoto/PFC group had a significantly lower ADP/ATP ratio compared with the M-HTK/PFC group, suggesting that different islet yields might be due to the differences as energy sources of the solutions used. In conclusion, M-Kyoto/PFC solution is better for pancreas preservation before islet isolation than M-HTK/PFC solution.


Asunto(s)
Histidina , Trasplante de Islotes Pancreáticos , Ácidos Cetoglutáricos , Páncreas/efectos de los fármacos , Inhibidores de Tripsina/farmacología , Tripsina , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Preservación de Órganos , Páncreas/metabolismo , Soluciones , Porcinos
17.
Cell Transplant ; 16(1): 75-83, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17436857

RESUMEN

Green tea polyphenols are known to protect allogenic donor tissues from acute rejection by their recipients. This immunosuppressive effect may be generated by a unique chemical property of the major component, epigallocatechin-o-gallate (EGCG), which can block specific cell surface molecules of the donor tissues. To test this hypothesis, we examined the effects of EGCG on the murine mixed lymphocyte reactions. EGCG treatment of stimulator cells significantly attenuated the proliferation of responder T cells. The proliferation did not recover upon the secondary stimulations by fresh untreated cells or exogenous IL-2. Flow cytometric analyses showed that EGCG treatment decreased the staining intensities of various cell surface molecules including MHC II, which plays a major role in antigen presentation, and B7.1, B7.2, and their ligand, CD28, which are required for costimulatory signals in T-cell activation. These results suggest that an anergic state of alloreactive T cells may be induced by either weakening of antigen signaling or blockage of costimulatory signals with EGCG. Other possible mechanisms behind the immunosuppressive effect and a potential use of EGCG treatment of donor tissues in transplantation medicine are discussed.


Asunto(s)
Catequina/análogos & derivados , Inmunosupresores/farmacología , Activación de Linfocitos/efectos de los fármacos , Animales , Apoptosis , Catequina/farmacología , Proliferación Celular , Células Cultivadas , Femenino , Flavonoides/farmacología , Citometría de Flujo , Interleucina-2/inmunología , Prueba de Cultivo Mixto de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Fenoles/farmacología , Extractos Vegetales/química , Polifenoles , Té/química
18.
Ann N Y Acad Sci ; 1079: 335-9, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17130575

RESUMEN

We performed the world's first successful living donor islet transplantation for unstable diabetes. A total of 408,114 islet equivalents were isolated from half a living pancreas and transplanted immediately to the recipient who was a 27-year-old female. The donor was a 56-year-old female in good health, mother of the recipient. The islets functioned immediately, and the recipient was weaned completely from insulin on the 22nd posttransplant day, and has maintained excellent glycemic control since. The donor was discharged on the 18th postoperative day with normal oral glucose tolerance test and without complications. Living donor islet transplantation could cure one insulin-dependent diabetes mellitus patients with a single donor. There are some advantages in the living donor islet transplantation: (a) living donor can alleviate the issue of donor shortage; (b) highly potent islets can be isolated from a living donor; and (c) the recipient can be treated with immunosuppressant and controlled blood glucose level tightly prior to the transplantation. These are important factors in overcoming the obstacles limiting islet transplantation. We believe that the living donor islet transplantation may become an additional option in treating insulin-dependent diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos , Donadores Vivos , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Basiliximab , Glucemia/metabolismo , Péptido C/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Infliximab , Insulina/uso terapéutico , Persona de Mediana Edad , Periodo Posoperatorio , Cuidados Preoperatorios , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Sirolimus/administración & dosificación , Sirolimus/uso terapéutico , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento
19.
Transplantation ; 82(5): 712-5, 2006 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-16969298

RESUMEN

Intraportal site is the standard for grafting in clinical islet transplantation. In the mouse model, the whole liver has been used as the grafting site to mimic clinical islet transplantation. However, this model lacks the potency to directly assess the contribution of the islet graft to diabetes control. Only demonstrating the immediate recurrence of diabetes in a surviving recipient after the removal of the islet graft can validate this assessment. In this study, we develop a mouse model of intraportal islet transplantation equipped with the potency of this assessment by injecting islets selectively into the right hepatic lobe under temporal clamp of the left portal vein. The mouse of this model survives after the right hepatectomy by which the islet graft is removed. This model can be applied to investigate both the specific graft-recipient interaction in the liver and the islet graft contribution to the control of diabetes.


Asunto(s)
Supervivencia de Injerto/fisiología , Trasplante de Islotes Pancreáticos/métodos , Hígado , Trasplante Heterotópico/métodos , Animales , Hepatectomía , Hígado/anatomía & histología , Ratones , Modelos Animales , Vena Porta/cirugía
20.
Transplantation ; 82(3): 327-31, 2006 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-16906029

RESUMEN

BACKGROUND: Recent advances in pancreatic islet transplantation (PIT) have contributed significantly to the treatment of patients with type 1 diabetes. The specific aim of this study was to develop an effective technique for the procurement of pancreas for PIT from nonheart-beating-donor (NHBDs). METHODS: Between January 2004 and August 2004, eight human pancreata were procured and processed for isolation of islets at a cell processing center. After confirmation of brain death status, a double balloon catheter was inserted to prevent warm ischemic damage to the donor pancreas by using an in situ regional organ cooling system that was originally developed for procurement of kidneys. The catheter position of the cooling system was modified specifically for the pancreas and kidney. Furthermore, we worked in cooperation with a kidney procurement team to protect the pancreas during kidney procurement. RESULTS: Warm ischemic time could be controlled with the modified in situ regional cooling system at 3.0 +/- 0.8 min (mean +/- SE). The operations for procurement of the kidneys and pancreata lasted 45.6 +/- 3.6 min and 10.6 +/- 1.8 min, respectively. Islet yield per isolation was 444,426 +/- 35,172 IE (islet equivalent). All eight cases met the criteria for PIT based on the Edmonton protocol. CONCLUSION: We developed a novel procurement technique in cooperation with our kidney procurement team. This protocol for the procurement of pancreas and kidney from a NHBD enabled us to transplant islets into a type 1 diabetic patient and kidney into a renal failure patient.


Asunto(s)
Trasplante de Islotes Pancreáticos/métodos , Donantes de Tejidos , Obtención de Tejidos y Órganos , Cadáver , Cateterismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
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