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1.
Transpl Int ; 37: 11336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962471

RESUMO

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.


Assuntos
Intestino Delgado , Células-Tronco Mesenquimais , Preservação de Órgãos , Ratos Endogâmicos Lew , Animais , Intestino Delgado/transplante , Ratos , Preservação de Órgãos/métodos , Masculino , Soluções para Preservação de Órgãos , Sobrevivência de Enxerto , Meios de Cultivo Condicionados , Proteína da Zônula de Oclusão-1/metabolismo , Claudina-3/metabolismo , Ratos Transgênicos , Glutationa , Rafinose , Alopurinol , Insulina , Adenosina
2.
Surgery ; 176(2): 469-476, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38811324

RESUMO

BACKGROUND: Adhesions between the abdominal wall and intestinal tract from previous surgeries can complicate reoperations; however, predicting the extent of adhesions preoperatively is difficult. This study aimed to develop a straightforward approach for predicting adhesion severity using a novel abdominal ultrasound technique that quantifies the displacement of motion vectors of two organs to enhance surgical safety. The efficacy of this methodology was assessed experimentally and clinically. METHODS: Using Aplio500T, a system we developed, we measured the displacement of the upper peritoneum and intestinal tract as a vector difference and computed the motion difference ratio. Twenty-five rats were randomized into surgery and nonsurgery groups. The motion difference ratio was assessed 7 days after laparotomy to classify adhesions. In a clinical trial, 51 patients undergoing hepatobiliary pancreatic surgery were evaluated for the motion difference ratio within 3 days preoperatively. Intraoperatively, adhesion severity was rated and compared with the motion difference ratio. A receiver operating characteristic curve was used to appraise the diagnostic value of the motion difference ratio. RESULTS: In the animal experiment, the adhesion group exhibited a significantly higher motion difference ratio than the no-adhesion group (0.006 ± 0.141 vs 0.435 ± 0.220, P < .001). In the clinical trial, the no-adhesion or no-laparotomy group had a motion difference ratio of 0.128 ± 0.074; mild-adhesion group, 0.143 ± 0.170; moderate-adhesion group, 0.326 ± 0.153; and high-adhesion group, 0.427 ± 0.152. The motion difference ratio receiver operating characteristic curve to diagnose the adhesion level (≥moderate) was 0.938, indicating its high diagnostic value (cut-off 0.204). CONCLUSION: This methodology may preoperatively predict moderate-to-high adhesions.


Assuntos
Parede Abdominal , Ultrassonografia , Aderências Teciduais/diagnóstico por imagem , Animais , Masculino , Humanos , Ratos , Parede Abdominal/cirurgia , Parede Abdominal/diagnóstico por imagem , Feminino , Ultrassonografia/métodos , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Idoso , Índice de Gravidade de Doença , Cuidados Pré-Operatórios/métodos , Intestinos/cirurgia , Intestinos/diagnóstico por imagem , Distribuição Aleatória , Curva ROC , Modelos Animais de Doenças
3.
J Clin Neurosci ; 124: 27-29, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640805

RESUMO

INTRODUCTION: Diabetes mellitus (DM) is known to be a cause of cervical internal carotid artery stenosis (ICS). In this study, we investigated the natural history of asymptomatic ICS in DM patients without surgical intervention. METHODS: We conducted a retrospective study of 148 DM patients with asymptomatic ICS treated medically at the Kansai Electric Power Hospital from April 2013 to March 2023, inclusive. We examined the incidence of ischemic stroke with ICS and evaluated the patients' clinical characteristics and imaging findings. RESULTS: Ischemic stroke with ICS occurred in 7 patients (4.7 %), and only smoking history was significantly correlated with the incidence of ischemic stroke (p = 0.04). DISCUSSION: The incidence rate of ischemic stroke with ICS in this study (4.7%) was comparable to the previous report. The result that, the correlated factors of the incidence of ischemic stroke in DM patients with ICS was only smoking history, seemed acceptable. However, prospective studies with a larger number of cases may be needed in the future to determine the correlated factors more eligibly.


Assuntos
Artéria Carótida Interna , Estenose das Carótidas , Humanos , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Artéria Carótida Interna/diagnóstico por imagem , Diabetes Mellitus/epidemiologia , Incidência , AVC Isquêmico/epidemiologia , AVC Isquêmico/etiologia , Idoso de 80 Anos ou mais , Complicações do Diabetes/epidemiologia
4.
Sci Rep ; 14(1): 4605, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409241

RESUMO

Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD.


Assuntos
Síndrome do Intestino Curto , Ratos , Animais , Masculino , Síndrome do Intestino Curto/metabolismo , Poliaminas/metabolismo , Ratos Sprague-Dawley , Ratos Endogâmicos Lew , Intestino Delgado/metabolismo , Dieta , Modelos Teóricos , Mucosa Intestinal/metabolismo
5.
J Neurosurg Case Lessons ; 7(3)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224584

RESUMO

BACKGROUND: Twig-like middle cerebral artery (T-MCA) is reported as a rare vascular anomaly characterized by reconstitution of the M1 segment of the middle cerebral artery (MCA) by a plexiform network of small vessels. Although it is generally believed that the etiology of T-MCA is an embryological persistence, some investigators have suggested that T-MCA may be a secondary consequence. Here, the authors report a second case of de novo T-MCA formation and reconsider the concept of T-MCA in connection with isolated MCA disease. OBSERVATIONS: A 40-year-old man's brain magnetic resonance imaging (MRI) checkup showed moderate stenosis of the M1 segment of the left MCA. Annual MRI follow-up was planned, and when performed 1 year later, it showed occlusion of the M1 segment of the left MCA. Cerebral angiography revealed occlusion of that M1 segment with abnormal arterial networks. This case was diagnosed as de novo T-MCA. The patient has remained asymptomatic for 2 years. LESSONS: The reports of de novo T-MCA indicate that acquired factors may be involved in the pathogenesis of T-MCA. We suggest that T-MCA should be defined as a variety of isolated MCA disease with new vessel formation.

6.
Ann Transplant ; 28: e941456, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38098225

RESUMO

BACKGROUND The management and fate of liver transplant (LT) recipients with preformed donor-specific antibodies (pDSA) remain controversial. The aim of this study was to evaluate the clinical impact of rituximab desensitization on pDSA in LT recipients. MATERIAL AND METHODS This retrospective observational study enrolled 120 LT patients aged ≥18 years. Patients with pDSA were administered 500 mg/body rituximab 1-21 days before LT, except for those who had an active infection or had insufficient time to receive rituximab. We allocated patients to groups with or without pDSA, and then divided patients with pDSA into rituximab (+) and rituximab (-) groups for further analysis. RESULTS Twenty-three patients (19.2%) with pDSA were identified. Of these, 18 received rituximab and 5 did not receive rituximab. No patients developed adverse events related to rituximab. In both groups, the levels of pDSA class I in all patients were decreased immediately after LT, whereas those of pDSA class II decreased slowly. There were no significant differences in pathology findings and overall survival between patients with pDSA who were rituximab (+) or rituximab (-), and between patients with or without pDSA. CONCLUSIONS Rituximab desensitization for LT patients with pDSA was managed successfully without significant complications. Due to the small sample size, we could not demonstrate the benefit of rituximab desensitization for LT patients compared with the rituximab (-) group. Additionally, clinical outcomes in patients with pDSA, with or without rituximab, were similar to those without pDSA. Rituximab desensitization might be not essential for LT.


Assuntos
Transplante de Rim , Transplante de Fígado , Humanos , Adolescente , Adulto , Rituximab/uso terapêutico , Transplante de Fígado/efeitos adversos , Transplante de Rim/efeitos adversos , Anticorpos , Doadores de Tecidos , Estudos Retrospectivos , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA
7.
Acta Neurochir (Wien) ; 165(12): 3637-3641, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37932634

RESUMO

Tyrosine kinase inhibitors (TKIs) have been widely used to treat chronic myeloid leukemia. Nilotinib and ponatinib, which are second- and third-generation TKIs, have been reported to cause cerebrovascular arterial complications. Here, we present two cases of moyamoya disease presenting with symptomatic ischemic stroke during new-generation TKI treatment. We judged that new-generation TKI treatment was a factor in symptomatic ischemic stroke of unknown moyamoya disease in both cases. Noninvasive examinations using magnetic resonance imaging or carotid ultrasonography should be performed before and during new-generation TKI treatment in order to prevent symptomatic ischemic stroke.


Assuntos
Antineoplásicos , AVC Isquêmico , Doença de Moyamoya , Humanos , Doença de Moyamoya/induzido quimicamente , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos
8.
Cancer Diagn Progn ; 3(5): 582-589, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671302

RESUMO

Aim: This study evaluated the relationship between the relative dose intensity (RDI) and the prognosis to assess the optimal duration of adjuvant chemotherapy for pancreatic cancer. Patients and Methods: From 2013 to 2018, 119 patients with pancreatic cancer underwent radical surgery. After excluding five patients who underwent R2 resection, three with stage IV disease, and two with adjuvant chemotherapy other than S-1, 109 cases were evaluated. They were classified into four groups based on the RDI for the total dosage of S-1: group 1: <50%, group 2: 50% to <80%, group 3: 80% to ≤125%, and group 4: >125%. Results: The number of patients in each group were 48, 20, 30 and 11, with median ages of 74, 73, 66 and 74, respectively. Median estimated glomerular filtration rate was 75, 72, 89 and 77 ml/min/1.73 m2, respectively, demonstrating statistically significant differences. The corresponding median and 5-year overall survival rates were: 378 days and 17.9%; 1,011 days and 35.1%; 1,246 days and 41.6%; 1,389 days and 10.6%. Using group 1 as a reference, the adjusted hazard ratio was 0.39 for group 2, 0.36 for group 3, and 0.30 for group 4; all were statistically significant. Conclusion: The higher the RDI of S-1 in adjuvant chemotherapy, the better the overall survival. Therefore, 1 year of adjuvant chemotherapy with S-1 in pancreatic cancer may be preferable to 6 months.

9.
Medicine (Baltimore) ; 102(38): e35324, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37746947

RESUMO

RATIONALE: The purpose of this case report is to describe a case of successful early rehabilitation intervention for simultaneous liver and kidney transplantation (SLKT). PATIENT CONCERNS: A 51-year-old Japanese man was diagnosed with Caroli disease 27 years ago. Hemodialysis was introduced due to end-stage renal disease 17 years ago. DIAGNOSES: After successful SLKT, the patient was extubated on postoperative day (POD) 1, liberated from dialysis on POD 4, and discharged from the intensive care unit on POD 9. INTERVENTIONS: Supervised rehabilitation was started on POD 2, and the patient was able to walk 100 m on POD 9. Electrical muscle stimulation therapy was started to improve muscle weakness in both legs on POD 16, and aerobic exercise using a cycle-ergometer was started on POD 24. OUTCOMES: The 6-minute walking distance improved from 324 m on POD 14 to 501 m on POD 28. The patient could walk 4000 to 5000 steps per day at hospital discharge, and was discharged home on POD 32. There were no adverse events, including worsening hepatic or renal function, during the rehabilitation period. One month after discharge, the patient was able to perform 30 to 40 minutes of aerobic exercise every day, and returned to work 5 months after discharge. LESSONS: This case shows that early rehabilitation intervention immediately after SLKT safely and rapidly improved physical performance without adverse events. The results in the present case suggest that regular physical assessment and appropriate interventions with a variety of exercise modalities can contribute to improved physical performance in SLKT patients.


Assuntos
Transplante de Rim , Transplante de Fígado , Masculino , Humanos , Pessoa de Meia-Idade , Diálise Renal , Doadores Vivos , Fígado
10.
Surg Case Rep ; 9(1): 100, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37286818

RESUMO

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in childhood. Stage 4S neuroblastoma is a unique subset of neuroblastoma characterized by a favorable course and potentially low malignancy with a high rate of spontaneous tumor regression. However, recent reports have shown that there is a subgroup of patients with stage 4S neuroblastoma characterized by MYCN amplification, chromosomal aberrations, age of < 2 months at diagnosis, and significantly poorer outcomes. CASE PRESENTATION: A 1-month-old male infant with a huge abdominal tumor was transferred to our hospital and diagnosed with stage 4S neuroblastoma. The patient showed respiratory distress due to abdominal compartment syndrome secondary to massive hepatic invasion, and he required a silo operation and mechanical ventilation. After chemotherapy using carboplatin and etoposide, the infiltrative massive hepatic invasion was resolved and the abdominal compartment syndrome gradually improved; however, liver dysfunction as evidenced by hyperbilirubinemia, coagulopathy, and hyperammonemia continued. At the age of 3 months, living-donor liver transplantation was performed for treatment of sustained liver failure using a reduced lateral segment graft from the patient's father. Post-transplant liver function recovered immediately. Examination of the explanted liver demonstrated that the majority of liver tissue had been replaced by fibroblastic cells after massive hepatocyte dropout. There were only small areas of residual neuroblastoma cells in the liver specimen. The patient was discharged from the hospital 5 months after transplantation with home intermittent respiratory support. At the time of this writing (23 months after liver transplantation), he was in good condition with no signs of recurrence of neuroblastoma. CONCLUSIONS: We have herein presented a case of successful pediatric living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma. Our case clearly shows that liver transplantation can be added as an appropriate extended treatment option for liver failure after resolution of stage 4S neuroblastoma.

12.
Surgery ; 172(2): 691-699, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35337684

RESUMO

BACKGROUND: The influence and risk associated with an aberrant right hepatic artery, a common anatomical variation, during pancreatoduodenectomy for pancreatic ductal adenocarcinoma has not been fully investigated. The present study analyzed the impact of an aberrant right hepatic artery on local recurrence after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. METHODS: A total of 169 patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy at 2 separate Japanese medical institutions were retrospectively analyzed. RESULTS: Thirty of 169 patients (17.7%) presented with an aberrant right hepatic artery. The incidence of local recurrence was higher in the aberrant right hepatic artery group than in the normal right hepatic artery group (43.3 vs 21.5%, P = .017). The local recurrence-free survival was significantly poorer in the aberrant right hepatic artery group than in the normal right hepatic artery group (P = .011). A multivariate analysis found that the aberrant right hepatic artery was an independent risk factor for local recurrence (hazard ratio: 3.74, P = .017). In the aberrant right hepatic artery group, more frequent local recurrence was observed in patients with tumors situated ≤10 mm from the aberrant right hepatic artery root. However, local recurrence was not observed in 2 out of 3 patients with tumors ≤10 mm from the aberrant right hepatic artery root who underwent pancreatoduodenectomy with combined resection of the aberrant right hepatic artery. CONCLUSION: The presence of an aberrant right hepatic artery in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma may be associated with an increased risk of postoperative local recurrence. Combined resection of the aberrant right hepatic artery may reduce local recurrence, especially for tumors near the root of the aberrant right hepatic artery.


Assuntos
Carcinoma Ductal Pancreático , Artéria Hepática , Recidiva Local de Neoplasia , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patologia , Artéria Hepática/patologia , Artéria Hepática/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Pancreaticoduodenectomia , Estudos Retrospectivos , Neoplasias Pancreáticas
13.
Surg Neurol Int ; 13: 57, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242423

RESUMO

BACKGROUND: Intracranial aneurysms of the distal middle cerebral artery are rare, and most etiologies are infection or dissection. We present an extremely rare intracranial fusiform thrombosed aneurysm of the distal middle cerebral artery with histopathological confirmation of a pseudoaneurysm. CASE DESCRIPTION: Our patient, a 68-year-old female, was previously healthy and had no history of infection or trauma. A fusiform thrombosed aneurysm of the distal middle cerebral artery was detected incidentally. The patient was treated successfully with trapping and resection of the aneurysm followed by superficial temporal artery to middle cerebral artery anastomosis. Xanthochromic and hypertrophic arachnoid membranes around the aneurysm were noticed, and a thrombus was detected inside the lesion. The aneurysmal wall had hyalinized connective tissue incompletely surrounded with intima, with no media or adventitia. Pathologically, it was a pseudoaneurysm. CONCLUSION: We report an extremely rare case of a pseudoaneurysm of the distal middle cerebral artery. We discuss the etiology of the lesion, with a literature review, and propose that the appearance and increase of the pseudoaneurysm was followed by microbleed of an aneurysm unrelated to the branching zone.

14.
Islets ; 14(1): 69-81, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35034568

RESUMO

The success of islet transplantation in both basic research and clinical settings has proven that cell therapy has the potential to cure diabetes. Islets intended for transplantation are inevitably subjected to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here, we found that protein factors secreted by porcine adipose-tissue mesenchymal stem cells (AT-MSCs) were capable of activating preserved porcine islets. A conditioned medium was prepared from the supernatant obtained by culturing porcine AT-MSCs for 2 days in serum-free medium. Islets were preserved at 4°C in University of Wisconsin solution during transportation and then incubated at 37°C in RPMI-1620 medium with fractions of various molecular weights prepared from the conditioned medium. After treatment with certain fractions of the AT-MSC secretions, the intracellular ATP levels of the activated islets had increased to over 160% of their initial values after 4 days of incubation. Our novel system may be able to restore the condition of isolated islets after transportation or preservation and may help to improve the long-term outcome of islet transplantation.Abbreviations: AT-MSC, adipose-tissue mesenchymal stem cell; Cas-3, caspase-3; DAPI, 4,6-diamidino-2-phenylindole; DTZ, dithizone; ES cell, embryonic stem cell; FITC, fluorescein isothiocyanate; IEQ, islet equivalent; INS, insulin; iPS cell, induced pluripotent stem cell; Luc-Tg rat, luciferase-transgenic rat; PCNA, proliferating cell nuclear antigen; PDX1, pancreatic and duodenal homeobox protein-1; UW, University of Wisconsin; ZO1, zona occludens 1.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Células-Tronco Mesenquimais , Adenosina , Trifosfato de Adenosina/metabolismo , Alopurinol , Animais , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Glutationa , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Soluções para Preservação de Órgãos , Rafinose , Ratos , Suínos
15.
Surg Today ; 52(5): 822-831, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34708306

RESUMO

PURPOSE: This study assessed the significance of measuring liver stiffness using virtual touch quantification before hepatectomy to predict posthepatectomy refractory ascites. METHODS: A total of 267 patients with hepatocellular carcinoma who underwent hepatectomy were prospectively analyzed. Liver stiffness was defined as the median value of the virtual touch quantification (Vs; m/s) by acoustic radio-force-impulse-based virtual touch. RESULTS: A multivariate analysis showed that Vs and the aspartate aminotransferase-to-platelet ratio index were independent risk factors for postoperative refractory ascites (odds ratio = 3.27 and 3.08, respectively). The cutoff value for Vs was 1.52 m/s (sensitivity: 59.5%, specificity: 88.6%) as determined by the analysis of the receiver-operating characteristic curve, and the area under the receiver-operating characteristic curve was 0.79. The cutoff value for the aspartate aminotransferase-to-platelet ratio was 0.952 (sensitivity: 65.5%, specificity: 82.9%), and the area under the receiver-operating characteristic curve was 0.75. CONCLUSIONS: Vs is an independent risk factor for refractory ascites after hepatectomy. The measurement of liver stiffness by virtual touch quantification before hepatectomy can help estimate the risk of postoperative refractory ascites. Nonsurgical treatments should be considered for the management of patients who are at high risk for refractory ascites.


Assuntos
Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Neoplasias Hepáticas , Ascite/etiologia , Aspartato Aminotransferases , Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Curva ROC
16.
Amino Acids ; 53(11): 1695-1703, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34654958

RESUMO

Polyamines are important to the survival and activation of organs and tissues via a homeostatic cell-metabolic process, and the polyamine content in cytoplasm decreases with aging. Decreases in cellular polyamine have been known to augment mutagenesis and cell death. Thus, supplementary polyamine in food is important to the prevention of aging. Here we show the anti-aging effects of oral intake of polyamine using luciferase-transgenic rats. Healthy rats, 10-12 weeks old, were given foods containing 0.01% and 0.1% (w/w) of polyamine, as compared a control food without polyamine, for 4 weeks. Using a bioimaging system, the photon intensities seen in the whole bodies and livers of rats consuming 0.1% of polyamine in food were stronger than those in rats consuming 0.01% and 0% of polyamine. However, there were no differences between groups in other characteristics, such as liver damage and body weight. In conclusion, we found that polyamine intake can activate cells throughout the whole body, providing an anti-aging effect.


Assuntos
Envelhecimento/metabolismo , Poliaminas/metabolismo , Animais , Transporte Biológico , Gerociência , Humanos , Fígado/metabolismo , Masculino , Camundongos Transgênicos , Ratos , Ratos Endogâmicos Lew
17.
Eur Surg Res ; 60(1-2): 63-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055575

RESUMO

BACKGROUND: It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. METHODS: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 µmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. RESULTS: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. CONCLUSION: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.


Assuntos
Regeneração Hepática/efeitos dos fármacos , Fígado/irrigação sanguínea , Poliaminas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Antígeno Ki-67/análise , Fígado/patologia , Masculino , Ratos , Ratos Endogâmicos Lew
18.
J Hepatobiliary Pancreat Sci ; 26(2): 73-81, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30561147

RESUMO

BACKGROUND: The purpose of this study was to examine the impact of pretreatments on outcomes after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). METHODS: From February 1999 to March 2015, 223 patients underwent LDLT for HCC. Until December 2006, there was no restriction in patient selection criteria regarding the number and size of tumors, following which we implemented the Kyoto criteria (tumor number ≤10, maximal diameter ≤5 cm, and des-gamma-carboxy prothrombin ≤400 mAU/ml) since January 2007. RESULTS: Of 223 patients, 156 had a history of pretreatments. Among 101 patients meeting the Milan criteria at the initial diagnosis, 38 progressed to beyond the criteria at liver transplantation (LT). Twenty-two out of 38 met the Kyoto criteria, and their survival and recurrence rates were significantly better than those of patients exceeding the Kyoto criteria (P = 0.004 and 0.035, respectively). Regarding the number of pretreatments (0 vs. 1-4 vs. ≥5), recurrence rate was significantly higher in the ≥5 pretreatments group than the 0 group. However, for patients meeting the Kyoto criteria, there were no significant differences in recurrence rates between these three groups. CONCLUSION: Better outcomes will be achieved by performing LT for HCCs meeting the Kyoto criteria even after repeated pretreatments.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Doadores Vivos , Seleção de Pacientes , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
World J Surg ; 42(1): 218-224, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28730553

RESUMO

BACKGROUND: Accurate preoperative estimation of graft weight is essential for improving outcomes in living donor liver transplantation. METHODS: This retrospective study sought to identify factors associated with graft weight overestimation. From April 2006 to August 2015, 340 living donors were assigned to no-overestimate (n = 284) or overestimate (n = 56) groups. We defined graft weight overestimation as a discrepancy ≥15% between estimated graft volume and actual graft weight. Donor data were compared, and associated factors for graft weight overestimation were analyzed. Recipient outcomes were compared between the groups according to identified factors. RESULTS: Donors were significantly younger in the overestimate group than in the no-overestimate group (35.0 vs. 46.0 years; p < 0.001). Multivariate analysis identified donor age <45 years as an independent risk factor for graft weight overestimation (odds ratio 2.068; 95% confidence interval 1.114-3.839; p = 0.021). Among recipients with donors <45 years (n = 168), incidence of small-for-size dysfunction (SFSD) was significantly higher in the overestimate group than in the no-overestimate group (7/37 patients vs. 7/131 patients; p = 0.016); no significant difference was observed among recipients with donors ≥45 years (n = 172). First-year mortality was lower in SFSD recipients with donors <45 years (14.3 vs. 60.9%, p = 0.007). Among recipients with younger donors, graft survival was not significantly different between overestimate and no-overestimate groups. CONCLUSIONS: Younger donor age was an independent risk factor for graft weight overestimation leading to SFSD in recipients, but did not impair graft survival.


Assuntos
Transplante de Fígado/efeitos adversos , Fígado/anatomia & histologia , Fígado/diagnóstico por imagem , Doadores Vivos , Complicações Pós-Operatórias , Adulto , Fatores Etários , Idoso , Feminino , Sobrevivência de Enxerto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tamanho do Órgão , Estudos Retrospectivos , Fatores de Risco
20.
Liver Transpl ; 23(9): 1171-1185, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28650112

RESUMO

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.


Assuntos
Fluorocarbonos/uso terapêutico , Transplante de Fígado/efeitos adversos , Soluções para Preservação de Órgãos/uso terapêutico , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Isquemia Quente/efeitos adversos , Adenosina/química , Adenosina/uso terapêutico , Aloenxertos/patologia , Alopurinol/química , Alopurinol/uso terapêutico , Animais , Modelos Animais de Doenças , Fluorocarbonos/química , Glutationa/química , Glutationa/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Insulina/química , Insulina/uso terapêutico , Fígado/patologia , Testes de Função Hepática , Transplante de Fígado/mortalidade , Masculino , Soluções para Preservação de Órgãos/química , Perfusão/métodos , Período Pós-Operatório , Rafinose/química , Rafinose/uso terapêutico , Ratos , Ratos Endogâmicos Lew , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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