Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 208
Filtrar
1.
Phys Rev E ; 106(2-2): 025205, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36109929

RESUMO

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

3.
Br J Surg ; 107(5): 586-594, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32162301

RESUMO

BACKGROUND: Japan Clinical Oncology Group (JCOG) 0212 (ClinicalTrials.gov NCT00190541) was a non-inferiority phase III trial of patients with clinical stage II-III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence-free survival (RFS). The planned primary analysis at 5 years failed to confirm the non-inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long-term follow-up data from JCOG0212. METHODS: Patients with clinical stage II-III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. RESULTS: A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7-year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non-inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). CONCLUSION: Long-term follow-up data did not support the non-inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.


ANTECEDENTES: El JCOG0212 (ClinicalTrials.gov: NCT00190541) fue un ensayo fase III de no inferioridad en pacientes con cáncer de recto en estadio clínico II/III sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. El ensayo comparó la escisión del mesorrecto (mesorectal excision, ME) con la ME con disección de los ganglios linfáticos laterales (lateral lymph node dissection, LLND), siendo el criterio de valoración principal la supervivencia libre de recidiva (recurrence free survival, RFS). El análisis primario planificado a los 5 años de seguimiento no pudo confirmar la no inferioridad de la ME frente a la ME con LLND. Este estudio tuvo como objetivo comparar la ME como procedimiento único y la ME con LLND utilizando datos de seguimiento a largo plazo del ensayo JCOG0212. MÉTODOS: En este estudio se incluyeron pacientes con cáncer de recto en estadio clínico II/III por debajo de la reflexión peritoneal sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. Después de que los cirujanos confirmaran la resección R0 mediante la ME, los pacientes fueron asignados al azar al brazo de ME sola o al brazo de ME con LLND. El criterio de valoración principal fue la supervivencia libre de recidiva (RFS). RESULTADOS: Un total de 701 pacientes de 33 instituciones fueron asignados al azar para ser tratados mediante una ME con LLND (n = 351) o EM sola (n = 350) entre junio de 2003 y agosto de 2010. Las tasas de RFS a 7 años fueron del 71,1% para ME con LLND y 70,7 % para ME sola (cociente de riesgos instantáneos, hazard ratio, HR: 1,09 (i.c. del 95% 0,84-1,42), no inferioridad P = 0,064)). El análisis de subgrupos mostró una mejor RFS entre los pacientes en estadio clínico III que se sometieron a ME con LLND en comparación con ME sola (HR: 1,49 (i.c. del 95%: 1,02-2,17)). CONCLUSIÓN: Los datos de seguimiento a largo plazo no justificaron la no inferioridad de la ME en comparación con la ME con LLND. Se recomienda la ME con LLND para pacientes en estadio clínico III, mientras que LLND podría omitirse para pacientes en estadio clínico II.


Assuntos
Excisão de Linfonodo , Protectomia/métodos , Neoplasias Retais/cirurgia , Intervalo Livre de Doença , Estudos de Equivalência como Asunto , Seguimentos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Retais/patologia
4.
Pharmazie ; 75(1): 2-6, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033625

RESUMO

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.


Assuntos
Acetaminofen/administração & dosagem , Excipientes/química , Povidona/química , Paladar , Acetaminofen/química , Acrilatos/química , Administração Oral , Liberação Controlada de Fármacos , Dureza , Concentração de Íons de Hidrogênio , Polímeros/química , Comprimidos , Resistência à Tração
5.
BJS Open ; 2(4): 195-202, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30079388

RESUMO

BACKGROUND: The optimal level for inferior mesenteric artery ligation during anterior resection for rectal cancer is controversial. The aim of this randomized trial was to clarify whether the inferior mesenteric artery should be tied at the origin (high tie) or distal to the left colic artery (low tie). METHODS: Patients were allocated randomly to undergo either high- or low-tie ligation and were stratified by surgical approach (open or laparoscopic). The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were duration of surgery, blood loss and 5-year overall survival. RESULTS: Some 331 patients entered the trial between June 2006 and September 2012. The trial was stopped prematurely as recruitment was slow. Seven patients were excluded after randomization but before operation because of procedural changes. High tie and low tie were performed in 164 and 160 patients respectively. The incidence of anastomotic leakage was not significantly different (17·7 versus 16·3 per cent respectively; P = 0·731). The incidence of severe complications requiring intervention was 2·4 versus 5·0 per cent for high and low tie respectively (P = 0·222). In multivariable analysis, risk factors for anastomotic leakage included male sex (odds ratio 4·36, 95 per cent c.i. 1·56 to 12·18) and distance of the tumour from the anal verge (odds ratio 0·99, 0·98 to 1·00). At 5 years there were no significant differences in overall (87·2 versus 89·4 per cent respectively; P = 0·386) and disease-free (76·3 versus 77·6 per cent; P = 0·765) survival. CONCLUSION: The level of ligation of the inferior mesenteric artery does not significantly influence the rate of anastomotic leakage. Registration number: NCT01861678 ( https://clinicaltrials.gov).

6.
Osteoporos Int ; 28(4): 1481-1490, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27933339

RESUMO

This study showed that bisphosphonate was safe and effective for the treatment of bone disorders in stage 4 chronic kidney disease (CKD) rats. Intermittent teriparatide therapy showed an anabolic action on bone even under secondary hyperparathyroidism conditions without having an adverse effect on mineral metabolism in late-stage CKD. INTRODUCTION: Patients with late-stage CKD are at high risk for fragility fractures. However, there are no consensus on the efficacy and safety of osteoporosis medications for patients with late-stage CKD. In the present study, we aimed to examine the efficacy and safety of alendronate (ALN) and teriparatide (TPD) for treating bone disorder in late-stage CKD with pre-existing secondary hyperparathyroidism using a rat model of CKD. METHODS: Male 10-week-old Sprague-Dawley rats were subjected to a 5/6 nephrectomy or sham surgery and randomized into the following four groups: sham, vehicle (saline subcutaneous (sc) daily), ALN (50 µg/kg sc daily), and TPD (40 µg/kg sc daily). Medications commenced at 24 weeks of age and continued for 4 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum assays were performed. RESULTS: Nephrectomized rats developed hyperphosphatemia, secondary hyperparathyroidism (SHPT), and high creatinine, equivalent to CKD stage 4 in humans. ALN suppressed the bone turnover and increased the degree of mineralization in cortical bone, resulting in an improvement in the mechanical properties. TPD further increased the bone turnover and significantly increased the degree of mineralization, micro-geometry, and bone volume, resulting in a significant improvement in the mechanical properties. Both ALN and TPD had no adverse effect on renal function and mineral metabolism. CONCLUSIONS: BP is safe and effective for the treatment of bone disorders in stage 4 CKD rats. Intermittent TPD therapy showed an anabolic action on bone even under SHPT conditions without having an adverse effect on mineral metabolism in late-stage CKD.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Hiperparatireoidismo Secundário/complicações , Hiperfosfatemia/complicações , Osteoporose/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Alendronato/efeitos adversos , Alendronato/farmacologia , Alendronato/uso terapêutico , Animais , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Masculino , Nefrectomia , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Ratos Sprague-Dawley , Teriparatida/farmacologia , Microtomografia por Raio-X
7.
Osteoporos Int ; 28(2): 709-718, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27704183

RESUMO

This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.


Assuntos
Artrite Experimental/complicações , Artrite Reumatoide/complicações , Osteoporose/etiologia , Animais , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/fisiopatologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Fenômenos Biomecânicos , Densidade Óssea/fisiologia , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/etiologia , Reabsorção Óssea/fisiopatologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Fêmur/fisiopatologia , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Osteoporose/fisiopatologia , Ovariectomia , Índice de Gravidade de Doença , Microtomografia por Raio-X
9.
Br J Surg ; 103(10): 1276-81, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27507715

RESUMO

BACKGROUND: The efficacy and safety of single-incision laparoscopic colectomy (SILC) for colonic cancer remain unclear. The aim of this study was to determine the outcomes of SILC compared with multiport laparoscopic colectomy (MPLC) for colonic cancer. METHODS: Patients with histologically proven colonic carcinoma located in the caecum, ascending, sigmoid or rectosigmoid colon, clinically diagnosed as stage 0-III by CT, were eligible for this study. Patients were randomized before surgery and underwent tumour dissection with complete mesocolic excision. Safety analyses were conducted according to randomization groups. RESULTS: A total of 200 patients were enrolled and randomized to the MPLC (100 patients) or SILC (100 patients) arm. Surgical outcomes were similar between the MPLC and SILC arms, including duration of operation (mean 162 versus 156 min respectively; P = 0·273), blood loss (mean 8·8 versus 21·4 ml; P = 0·102), conversion to open laparotomy (2·0 versus 1·0 per cent; P = 0·561), reoperation (3·0 versus 3·0 per cent; P = 1·000), time to first flatus (both median 1 day; P = 0·155) and postoperative hospital stay (both median 6; P = 0·372). The total skin incision length was significantly shorter in the SILC arm (mean 4·4 cm versus 6·8 cm in the MPLC arm; P < 0·001). The median duration of analgesia use was 5 days in the MPLC and 4 days in the SILC arm (P = 0·485). Overall complication rates were equivalent (15·0 versus 12·0 per cent respecitvely; P = 0·680). CONCLUSION: SILC is not superior to MPLC. REGISTRATION NUMBER: UMIN000007220 (http://www.umin.ac.jp/ctr/index.htm).


Assuntos
Adenocarcinoma/cirurgia , Colectomia/métodos , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
10.
Eur J Surg Oncol ; 42(12): 1851-1858, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27519616

RESUMO

BACKGROUND: We conducted a randomized controlled trial (JCOG0212) to determine whether the outcome of mesorectal excision (ME) alone for rectal cancer is not inferior to that of ME with lateral lymph node dissection (LLND). The present study focused on male sexual dysfunction after surgery. METHODOLOGY: Eligibility criteria included clinical stage II/III rectal cancer, the lower margin of the lesion below the peritoneal reflection, the absence of lateral pelvic lymph node enlargement, and no preoperative radiotherapy. After confirmation of R0 resection by ME, patients were intraoperatively randomized. Questionnaires using the International Index of Erectile Function (IIEF-5) about the sexual function of men were collected before and 1 year after surgery. Sexual dysfunction incidence was defined as the ratio of patients showing sexual dysfunction after surgery relative to the number who had no erectile dysfunction before surgery. RESULTS: Among 701 patients enrolled between June 2003 and August 2010, 472 males were included. Among them, 343 (73%) completed preoperative and postoperative questionnaires. According to the study protocol, the incidences of sexual dysfunction in patients who underwent ME alone and ME with LLND were 68% (17/25; 95%CI, 47-85%) and 79% (23/29; 95%CI, 60-92%), respectively (p = 0.37). Incidences of sexual dysfunction in patients with no or only mild erectile dysfunction before surgery who underwent ME alone and ME with LLND were 59% (48/81) and 71% (67/95), respectively (p = 0.15). Multivariate analysis identified age as the only risk factor for sexual dysfunction after surgery (p = 0.02). CONCLUSIONS: LLND may not increase sexual dysfunction incidence after rectal cancer surgery. This incidence is associated with increased age. This trial is registered with ClinicalTrials.gov, number NCT00190541 and University Hospital Medical Information Network Clinical Trials Registry, number C000000034.


Assuntos
Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Disfunção Erétil/epidemiologia , Excisão de Linfonodo/métodos , Mesentério/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Adenocarcinoma/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Disfunções Sexuais Fisiológicas/epidemiologia
11.
Dis Esophagus ; 29(8): 1071-1080, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26471766

RESUMO

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes.


Assuntos
Neoplasias Esofágicas/terapia , Indicadores Básicos de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Intervalo Livre de Doença , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Hipoalbuminemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Albumina Sérica/análise , Resultado do Tratamento
12.
Hepatogastroenterology ; 62(137): 30-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25911862

RESUMO

BACKGROUND/AIMS: Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage. METHODOLOGY: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study. RESULTS: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter. CONCLUSION: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.


Assuntos
Fístula Anastomótica/terapia , Colectomia/efeitos adversos , Neoplasias Colorretais/cirurgia , Alimentos Formulados , Nutrição Parenteral Total , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/dietoterapia , Fístula Anastomótica/etiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Alimentos Formulados/efeitos adversos , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral Total/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
Colorectal Dis ; 17(2): 133-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25204386

RESUMO

AIM: The indications for intersphincteric (ISR) anterior resection are not clearly defined. The aim of this study was to evaluate vertical extension of T2 or T3 low rectal cancer treated by rectal amputation to optimize patient selection for ISR. METHOD: The abdominoperineal excision specimens of T2 or T3 low rectal cancer from 53 patients treated between 1992 and 2004 were retrospectively reviewed. Vertical invasion was quantified by measuring the shortest distance between the tumour and the striated muscle (T-SM), assuming that this represented the surgical margin that would have be achieved had an ISR been performed. RESULTS: Involvement of the dentate line (DL) and intramural distal spread were independent risk factors for T-SM ≤ 2 mm. The T-SM was less when the inferior border of the tumour was on the distal side of the DL (r = 0.572, P < 0.001). The probability of involvement of the DL, intramural distal spread or either one of these being associated with T-SM ≤ 2 mm was 43, 46 and 43%, respectively. All patients without both intramural distal spread and involvement of the DL had T-SM > 2. CONCLUSION: We recommend that ISR should only be performed for patients with T2 or T3 low rectal cancer in whom the lowest edge of the tumour is above the DL and there is no intramural distal spread. Such patients are relatively unlikely to have a T-SM ≤ 2 mm.


Assuntos
Canal Anal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Seleção de Pacientes , Diafragma da Pelve/patologia , Neoplasias Retais/cirurgia , Idoso , Canal Anal/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Diafragma da Pelve/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco
14.
J Dent Res ; 94(1): 121-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25376721

RESUMO

Nuclear factor kappa B (NF-κB) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-κB signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-κB signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKKß, an essential component of the NF-κB pathway, under keratin 5 promoter (K5-Ikkß). K5-Ikkß mice showed supernumerary incisors whose formation was accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is normally observed in wild-type incisor epithelium was reduced in K5-Ikkß mice. The supernumerary incisors in K5-Ikkß mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions.


Assuntos
Incisivo/embriologia , NF-kappa B/fisiologia , Odontogênese/fisiologia , Germe de Dente/embriologia , Proteínas Adaptadoras de Transdução de Sinal , Ameloblastos/citologia , Amelogenina/análise , Animais , Apoptose/fisiologia , Proteínas Morfogenéticas Ósseas/genética , Esmalte Dentário/citologia , Epitélio/embriologia , Proteínas Hedgehog/fisiologia , Quinase I-kappa B/fisiologia , Imageamento Tridimensional/métodos , Incisivo/anormalidades , Queratina-15/genética , Camundongos , Camundongos Mutantes , Microrradiografia/métodos , Mutação/genética , Receptores Patched , Fenótipo , Regiões Promotoras Genéticas/genética , Receptores de Superfície Celular/fisiologia , Germe de Dente/anormalidades , Dente Supranumerário/etiologia , Dente Supranumerário/genética , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia , Microtomografia por Raio-X/métodos
16.
Horm Metab Res ; 47(6): 433-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25011018

RESUMO

Synthetic glucocorticoids such as dexamethasone are widely used to treat a variety of inflammatory and autoimmune conditions, but they may induce adverse events including hyperglycemia. To shed light on the effect and action mechanism of dexamethasone, we examined the alterations of gene expression levels caused by dexamethasone.Microarray analysis was performed on whole blood collected from 24 physically healthy subjects at baseline and after dexamethasone administration. The expression levels of resistin mRNA were found to be significantly increased after the dexamethasone administration. In a separate sample of 12 subjects, we examined plasma resistin protein levels and found that they were increased after dexamethasone administration. Furthermore, the plasma mRNA and protein levels of resistin were significantly higher in individuals who carried the A allele of RETN single nucleotide polymorphism rs3219175 than in those who did not carry the allele. There was no significant interaction between the genotype and dexamethasone administration. No significant correlation was found between plasma levels of cortisol and resistin. Consistent with previous studies, the genotype of RETN rs3219175 was a strong determinant of resistin levels. The present study showed that oral administration of dexamethasone increases the protein and mRNA levels of resistin irrespective of the rs3219175 genotype.


Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Resistina/metabolismo , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resistina/genética
17.
Br J Cancer ; 111(2): 365-74, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24921913

RESUMO

BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples. RESULTS: CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.


Assuntos
Neoplasias Colorretais/metabolismo , Receptores de Hialuronatos/metabolismo , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Receptores de Hialuronatos/genética , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Peptídeos/genética , Peptídeos/metabolismo , Prognóstico , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Hernia ; 18(6): 845-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24435318

RESUMO

PURPOSE: This retrospective study evaluates the clinical course and outcomes of patients who underwent surgery for strangulated hernias. METHODS: Among 520 groin hernias from 2001 to 2012, 51 inguinal and 42 femoral hernias were strangulated and operated emergently at a tertiary referral center. Perioperative factors, patient profiles, and time interval to surgery (T total = time from onset to surgery, T 1 = time from onset to initial evaluation, T 2 = time from the first hospital to the tertiary center, T 3 = time from admission at the tertiary center to surgery, T total = T 1 + T 2 + T 3) were analyzed in patients with strangulation, then compared between two groups, the bowel resection (BR) group and the non-bowel resection (NBR) group. RESULTS: T 1, T 2 and T total in the bowel resection group were significantly longer than those in the non-bowel resection group (P < 0.05). Patients who presented initially to the tertiary center (T 2 = 0) had a significantly lower resection rate than patients transported from other hospitals (24 vs. 44 %, P = 0.048). There was no significant difference in morbidity between the BR and NBR groups (35 vs. 24 %, P = 0.231). CONCLUSIONS: The elapsed time from onset to surgery, especially T 1 and T 2, is the most important prognostic factor in patients with strangulated groin hernias. Early diagnosis and transportation are essential for good outcomes.


Assuntos
Hérnia Femoral/cirurgia , Hérnia Inguinal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Emergências , Feminino , Hérnia Femoral/complicações , Hérnia Inguinal/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
19.
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
20.
AJNR Am J Neuroradiol ; 34(3): 524-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22899787

RESUMO

BACKGROUND AND PURPOSE: Restriction of diffusion has been reported in the early phase of secondary neuronal degeneration, such as wallerian degeneration. The purpose of this study was to investigate postoperative transient reduced diffusion in the ipsilateral striatum and thalamus as a remote effect of surgery. MATERIALS AND METHODS: Six hundred two postoperative MR imaging examinations in 125 patients after cerebral surgery were retrospectively reviewed, focusing on the presence of reduced diffusion in the striatum and/or thalamus. The distribution of reduced diffusion in the striatum was classified into 3 groups: anterior, central, and posterior. Reduced diffusion in the thalamus was also classified on the basis of the anatomic locations of the thalamic nuclei. Further follow-up MRI was available in all patients with postoperative reduced diffusion, and acute infarctions were excluded. The patient medical records were reviewed to evaluate neurologic status. RESULTS: Restriction of diffusion was observed in the striatum and/or thalamus ipsilateral to the surgical site in 17 patients (13.6%). The distribution of signal abnormality correlated with the location of the operation, in concordance with the architecture of the striatocortical and thalamocortical connections. Reduced diffusion was observed from days 7 to 46 after the operation, especially during days 8-21. The signal abnormalities completely resolved on follow-up examinations. The median follow-up period was 202 days (interquartile range, 76-487 days). CONCLUSIONS: Postoperative transient reduced diffusion in the ipsilateral striatum and/or thalamus likely represents an early phase of secondary neuronal degeneration based on its characteristic distribution and time course. Clinically, this reduced diffusion should not be mistaken for postoperative ischemic injury.


Assuntos
Corpo Estriado/patologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Tálamo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Medição de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA