Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
1.
Tech Coloproctol ; 27(12): 1387-1392, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37358669

RESUMO

PURPOSE: Stoma site marking is an important preoperative intervention for preventing various stoma-associated complications. In our institution, standardized stoma site marking is routinely performed before rectal cancer surgery with stoma creation, and various stoma-associated factors are recorded in the ostomy-record template. The present study investigated risk factors for stoma leakage. METHODS: Our stoma site marking is standardized so that it can be performed by non-stoma specialists. To identify risk factors of stoma leakage at 3 months after surgery, various preoperative factors associated with stoma site marking in our ostomy-record template were retrospectively analyzed in 519 patients who underwent rectal cancer surgery with stoma creation from 2015 to 2020. RESULTS: Stoma leakage was seen in 35 of the 519 patients (6.7%). The distance between the stoma site marking and the umbilicus was less than 60 mm in 27 of the 35 patients (77%) who experienced stoma leakage, so a distance of less than 60 mm was identified as an independent risk factor for stoma leakage. Aside from preoperative factors, stoma leakage was also caused by postoperative skin wrinkles or surgical scars near the stoma site in 8 of 35 patients (23%). CONCLUSION: Preoperative standardized stoma site marking is necessary to achieve reliable marking that is easy to perform. To reduce the risk of stoma leakage, a distance of 60 mm or more between the stoma site marking and the umbilicus is ideal, and surgeons need to contrive ways to keep surgical scars away from the stoma site.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Estomas Cirúrgicos , Humanos , Estudos Retrospectivos , Cicatriz , Estomas Cirúrgicos/efeitos adversos , Laparoscopia/efeitos adversos , Neoplasias Retais/cirurgia , Padrões de Referência
4.
BJS Open ; 3(6): 822-829, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832589

RESUMO

Background: There is a lack of large studies focusing on the prognostic significance of lateral lymph node (LLN) metastasis following LLN dissection (LLND) in rectal cancer. The aim of this study was to evaluate the prognostic impact of LLN metastases on survival of patients with advanced low rectal cancer. Methods: Consecutive patients with locally advanced, but not metastatic, extraperitoneal rectal cancer treated with neoadjuvant (chemo)radiotherapy plus total mesorectal excision between 2004 and 2015 were included in the study. LLND was performed when pretreatment imaging documented enlarged LLNs (7 mm or greater in size). Localization of nodal metastases and long-term outcomes were analysed. Kaplan-Meier analysis was used to compare the survival of patients with ypN0 disease with that of patients with mesorectal ypN+/LLN- status and patients with positive LLNs. The Cox proportional hazards model was used to evaluate predictors of disease-free survival (DFS) and local recurrence. Results: A total of 613 patients were included in the study; LLND was performed in 212 patients (34·6 per cent) and 57 (9·3 per cent) had LLN metastasis. Patients with LLN metastasis had improved DFS and local recurrence cumulative incidence rates compared with patients with mesorectal ypN2+/LLN- disease (DFS: P = 0·014; local recurrence: P = 0·006). Although the DFS rate of patients with LLN metastasis was worse than that of patients with ypN0 disease (P < 0·001), the cumulative incidence of local recurrence was similar (P = 0·491). In multivariable analysis, residual LLN metastasis was not an independent predictor of worse DFS or local recurrence. Conclusion: LLN metastasis is not an independent predictor of local recurrence or survival. Survival of patients presenting with LLN metastasis after (chemo)radiotherapy was intermediate between that of patients with ypN0 status and those with mesorectal ypN2 positivity.


Antecedentes: No existen en la literatura grandes estudios dirigidos a investigar la importancia pronóstica de las metástasis en los ganglios linfáticos laterales (lateral lymph nodes, LLN) después de la disección de los mismos (LLN dissection, LLND) en pacientes con cáncer de recto. El objetivo de este estudio fue evaluar el impacto pronóstico de las metástasis en los LLN sobre la supervivencia de los pacientes con cáncer de recto. Métodos: Se analizaron 613 pacientes consecutivos con cáncer de recto localmente avanzado extraperitoneal y no metastásico tratados con (quimio)radioterapia neoadyuvante seguida de resección total del mesorrecto (total mesorectal excision, TME) entre 2004 y 2015. Se realizó una LLND cuando el estudio mediante pruebas de imagen previo el tratamiento mostró LLN aumentados de tamaño ≥ 7 mm. Se analizó la localización de las metástasis ganglionares y los resultados a largo plazo. El análisis de supervivencia se realizó mediante el método de Kaplan­Meier para comparar las supervivencias de los pacientes ypN0 frente a los pacientes ypN con positividad mesorrectal/LLN negativos y frente a los pacientes LLN positivos. Se utilizó el modelo de riesgo proporcional de Cox para evaluar los factores predictivos de supervivencia libre de enfermedad y de recidiva local. Resultados: Se realizó una LLND en 212 (34,6%) pacientes, y 57 (9,3%) pacientes presentaban metástasis en los LLN. Los pacientes con metástasis en los LLN presentaron mejores curvas de incidencia acumulada de recidiva local y de supervivencia libre de enfermedad en comparación con los pacientes con ganglios mesorrectales ypN2 positivos/LLN negativos (respectivamente, P = 0,0135 y P = 0,0060). Aunque la curva de la supervivencia libre de enfermedad de los pacientes con metástasis en los LLN fue peor que la de los pacientes ypN0 (P < 0,0001), la incidencia acumulada de recidiva local fue similar (P = 0,4905). En el análisis multivariable, la metástasis residual en los LLN no fue un factor predictivo independiente de peor supervivencia libre de enfermedad ni de recidiva local. Conclusión: Las metástasis en los LLN no es un factor predictivo independiente de recidiva local o supervivencia. Los pacientes que presentaron metástasis en los LLN después de (quimio)radioterapia mostraron características de supervivencia intermedias entre ypN0 y pacientes con ganglios mesorrectales ypN2 positivos.


Assuntos
Metástase Linfática/terapia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/diagnóstico , Protectomia , Neoplasias Retais/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Incidência , Estimativa de Kaplan-Meier , Leucovorina/uso terapêutico , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasia Residual , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/patologia , Reto/cirurgia , Estudos Retrospectivos
5.
Colorectal Dis ; 17(10): O213-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26277783

RESUMO

AIM: The lateral pelvic lymph nodes are one of the major sites and sources of local recurrence (LR) after surgery for rectal cancer. Salvage lateral pelvic lymph node dissection (LPLD) is potentially curative, but the value of laparoscopic surgery in such cases is unknown. Our aim was to report the technical details of laparoscopic salvage LPLD for LR at these nodes after rectal cancer surgery. METHOD: The study was based on nine patients who underwent laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes after surgery for rectal cancer. The safety and feasibility of this procedure were determined. RESULTS: The median operation time was 381 min and the median estimated blood loss was 130 ml. There were no conversions. Adjacent structures removed en bloc were the pelvic plexus in four patients, the internal iliac artery in seven patients and the seminal vesicle in one patient. The median number of metastatic lymph nodes was 1 (range 1-11). CONCLUSION: Our novel technique of laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes is safe and feasible.


Assuntos
Laparoscopia/métodos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Terapia de Salvação , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Pelve , Neoplasias Retais/patologia , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
6.
Allergy ; 69(5): 668-73, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24673601

RESUMO

BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. METHODS: In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS: Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/µl) in the high serum periostin group. CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.


Assuntos
Asma/genética , Asma/fisiopatologia , Variação Genética , Receptores de Glucocorticoides/genética , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Asma/tratamento farmacológico , Asma/imunologia , Moléculas de Adesão Celular/sangue , Eosinófilos/imunologia , Feminino , Volume Expiratório Forçado , Estudos de Associação Genética , Proteínas de Choque Térmico/genética , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Testes de Função Respiratória , Fatores de Risco
7.
Br J Cancer ; 110(2): 469-78, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24346288

RESUMO

BACKGROUND: Interleukin-6 (IL-6) has an important role in cancer progression, and high levels of plasma IL-6 are correlated with a poor prognosis in a variety of cancers. It has also been reported that tumour stromal fibroblasts are necessary for steps in cancer progression, such as angiogenesis. There have been few reports of a correlation between fibroblast actions and IL-6 levels. In this study, we examined the correlation between cancer stromal fibroblasts and IL-6 and the utility of IL-6 as a therapeutic target in human colon cancer. METHODS: The expression levels of IL-6 and VEGF of fibroblasts and cancer cell lines were evaluated using real-time PCR and ELISA. The anti-angiogenic effect of inhibiting IL-6 signalling was measured in an angiogenesis model and animal experiment. RESULTS: We demonstrate that stromal fibroblasts isolated from colon cancer produced significant amounts of IL-6 and that colon cancer cells enhanced IL-6 production by stromal fibroblasts. Moreover, IL-6 enhanced VEGF production by fibroblasts, thereby inducing angiogenesis. In vivo, anti-IL6 receptor antibody targeting stromal tissue showed greater anti-tumour activity than did anti-IL6 receptor antibody targeting xenografted cancer cells. CONCLUSION: Cancer stromal fibroblasts were an important source of IL-6 in colon cancer. IL-6 produced by activated fibroblasts induced tumour angiogenesis by stimulating adjacent stromal fibroblasts. The relationship between IL-6 and stromal fibroblasts offers new approaches to cancer therapy.


Assuntos
Anticorpos/farmacologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/tratamento farmacológico , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Receptores de Interleucina-6/metabolismo , Células Estromais/efeitos dos fármacos , Animais , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Fibroblastos/patologia , Células HT29 , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Nus , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Células Estromais/metabolismo , Células Estromais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Clin Exp Allergy ; 43(6): 608-15, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23711122

RESUMO

BACKGROUND: Epidemiological studies have shown that smoking increases the propensity for atopy and asthma. However, the effects of smoking on atopy and eosinophilic inflammation in asthmatics, including the elderly, remain unknown. OBJECTIVE: To determine the effects of smoking on serum immunoglobulin E (IgE) levels and eosinophilic inflammation in asthmatics of all ages. METHODS: The associations of serum IgE levels, blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels with smoking and age in steroid-naive asthmatics were cross-sectionally assessed (n = 307). Levels of sputum eosinophil and thymic stromal lymphopoietin (TSLP) that promotes Th2 inflammation were also analysed. Current smokers were excluded when analysing contributing factors of FeNO. RESULTS: Levels of serum IgE, blood eosinophil and FeNO decreased with increasing age in never-smokers, whereas decrease in serum IgE levels with increasing age was not observed in current smokers. In addition, current smoking was associated with higher blood eosinophil counts. In atopic asthmatics, age-related declines in serum IgE levels were less steep in ex-smokers than in never-smokers, and atopic ex-smokers with asthma showed higher blood eosinophil counts and higher FeNO irrespective of age. Lastly, sputum TSLP levels were associated with sputum eosinophil proportions and pack-years. Current and ex-smokers had higher TSLP levels than never-smokers. CONCLUSIONS AND CLINICAL RELEVANCE: In steroid-naive asthmatics, smoking may attenuate the age-related decrease in IgE levels and maintain eosinophilic inflammation, in which TSLP may be involved.


Assuntos
Eosinófilos/imunologia , Imunoglobulina E/imunologia , Inflamação/imunologia , Fumar , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Asma/imunologia , Asma/metabolismo , Estudos Transversais , Citocinas/metabolismo , Expiração , Feminino , Compostos Férricos/sangue , Humanos , Imunoglobulina E/sangue , Inflamação/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Óxido Nítrico , Escarro/metabolismo , Adulto Jovem , Linfopoietina do Estroma do Timo
9.
Dentomaxillofac Radiol ; 39(2): 65-71, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20100916

RESUMO

OBJECTIVE: The aim was to evaluate the possibility of radiographic prediction of the prognosis of simple bone cysts (SBCs) of the jaws. METHODS: The relationship between the radiographic findings and treatment outcome (healing or recurrence) was investigated in 31 cases treated in the authors' hospital and 108 published cases. RESULTS: In 17 of our 31 cases, the lesions had radiographic findings of a preserved lamina dura adjacent to the lesion, with a smooth margin, and no or smooth bone expansion, and all of them healed after surgery. In the other 14 cases, there was resorption of the lamina dura, a scalloped margin, nodular bone expansion, root resorption, a sclerotic mass or multiple cavities, and nine cases of recurrence. Although there was incomplete information in the published case studies, similar results were noted. CONCLUSIONS: It was concluded that there was a relationship between the radiographic features of the lesions and prognosis. Radiographic examination should be used not only for discovering and diagnosing the lesions, but also for predicting possible prognosis.


Assuntos
Cistos Maxilomandibulares/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligamento Periodontal/diagnóstico por imagem , Prognóstico , Radiografia , Recidiva , Estudos Retrospectivos , Reabsorção da Raiz/diagnóstico por imagem , Adulto Jovem
10.
Acta Chir Belg ; 108(5): 532-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19051461

RESUMO

AIMS: Anatomic resection, i.e., systematic removal of a liver segment confined by portal branches, is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). The procedure may reduce tumour recurrence and enhance survival of HCC patients. To determine the significance of anatomic resection for HCC patients, we retrospectively conducted a comparative analysis between anatomic (AR) and non-anatomic liver resection (NAR) in 113 Japanese HCC patients with a solitary tumour, a tumour located within one segment, absence or invasion of distal to second order branches of the portal vein, and absence or invasion of peripheral branches of the hepatic vein. METHODS: Patients were divided into two groups, AR group (n = 49) and NAR group (n = 64). RESULTS: The prevalence of liver damage Grade B in the NAR group was significantly greater than in the AR group (p < 0.05). Tumour-free and overall survival following liver resection was not significantly different between AR and NAR groups. In the NAR group, tumour-free and overall survival in patients with tumour exposure at the surgical margin was significantly lower than with a surgical margin greater than 0 mm (not exposed) (p < 0.05). Survival between the AR and NAR groups without tumour exposure at the surgical margin was similar. CONCLUSIONS: Anatomic resection is the theoretical aim. In HCC patients with impaired liver functions, limited liver resection without tumour exposure may provide longer tumour-free and overall survival.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Idoso , Ascite/epidemiologia , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
11.
Dentomaxillofac Radiol ; 34(2): 126-31, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15829698

RESUMO

Metastatic retinoblastoma of the jaws is very rare. We present a 4-year-old boy with metastatic retinoblastoma that involved both the maxilla and mandible simultaneously. Enhanced CT indicated bone-destructive masses with partially non-enhanced area and enhanced margin in the right maxilla and left mandible. MRI showed well-delineated masses that were isointense on T(1) weighted images and hyperintense on T(2) weighted images. Four weeks after chemotherapy and bone marrow transplantation, the size of lesions remarkably decreased. The patient died 19 months later with extensive tumour metastases despite additional chemotherapy. In this case, the dental crypt of a permanent tooth was considered the potential target through which retinoblastoma metastasized to the jaws.


Assuntos
Neoplasias Oculares/patologia , Neoplasias Mandibulares/secundário , Neoplasias Maxilares/secundário , Retinoblastoma/secundário , Pré-Escolar , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/patologia , Neoplasias Maxilares/diagnóstico por imagem , Neoplasias Maxilares/patologia , Radiografia Panorâmica , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/patologia , Tomografia Computadorizada por Raios X
12.
Exp Eye Res ; 78(3): 591-7, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15106939

RESUMO

A novel microscope system is presented for observation of corneal cells in a living mouse. It enables tracking of individual cells in all layers of the cornea at various times, thus allowing the generation of time-lapse recordings. The system consists of three major components: an upright fluorescence microscope for visualization of corneal cells, a mouse-holding unit for immobilization of the animal and the eye, and a set of gimbals which permit observation of a wide area of corneal surface without refocusing. The same cells could be observed at different limes with the help of fiducial marks in the cornea, allowing their changes in position to be determined under natural and experimental conditions. This technique should prove useful in investigation of the cell movement in normal and diseased corneas, including the study of wound healing after an injury or surgery.


Assuntos
Córnea/citologia , Animais , Movimento Celular , Substância Própria/citologia , Movimentos Oculares , Imobilização , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microscopia de Fluorescência/instrumentação , Microscopia de Fluorescência/métodos
13.
Arch Biochem Biophys ; 391(2): 265-70, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11437358

RESUMO

As we previously reported, 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) dose-dependently inhibited not only proliferation of undifferentiated murine erythroleukemia (MEL) cells but also activin A-induced erythroid differentiation of MEL cells. However, the effect of 1,25(OH)2D3 on MEL cell proliferation was significantly greater by one order of magnitude than that on differentiation (IC(50): 9.2 vs 0.8 nM, respectively). The response of activin A-treated mature MEL cells to 1,25(OH)2D3 in the induction of 1,25(OH)2D3-24-hydroxylase (24-OHase) activity, a rapid effect of 1,25(OH)2D3, was enhanced to the same degree as in untreated immature cells, suggesting that differences in capacity of cells to inactivate 1,25(OH)2D3 did not contribute to augmentation of 1,25(OH)2D3 effect in activin A-treated mature cells. Furthermore, neither the number nor the affinity of vitamin D receptors (VDR) differed significantly between activin A-treated cells and untreated immature cells. The intracellular cAMP level, which affects 1,25(OH)2D3-mediated induction of 24-OHase activity, was significantly less in activin A-treated mature cells than in immature MEL cells. The addition of dibutyryl cAMP (dbc AMP) to activin A-treated MEL cells dose-dependently attenuated 1,25(OH)2D3-mediated induction of 24-OHase activity, finally to a level comparable to that of the untreated cells at the final concentration of 100 nM dbcAMP, while dbcAMP itself by 100 nM did not affect MEL cell differentiation by 24 h. In summary, we have shown for the first time that 1,25(OH)2D3 exerted its effect on leukemia cells at physiological concentration and that the magnitude of this effect depended on the changes in intracellular cAMP level through stages of differentiation, suggesting that the cAMP-protein kinase A system may be useful as a target for clinical application of vitamin D analogs by improving the sensitivity of leukemic cells to 1,25(OH)2D3.


Assuntos
Diferenciação Celular/efeitos dos fármacos , AMP Cíclico/farmacologia , Esteroide Hidroxilases/farmacologia , Ativinas , Animais , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Indução Enzimática , Inibinas/farmacologia , Camundongos , Oxigenases de Função Mista/biossíntese , Receptores de Calcitriol/metabolismo , Trítio , Células Tumorais Cultivadas , Regulação para Cima/efeitos dos fármacos
14.
Bioorg Med Chem Lett ; 11(4): 545-8, 2001 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-11229767

RESUMO

We synthesized 4-chlorophenethylaminoquinazoline derivatives and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. Compound 2f, containing a piperazine ring at the C(7)-position of the quinazoline ring, exhibited more potent inhibitory activities toward both than the lead compound la. A smaller N-substituent in the piperazine ring was required for inhibition of TNF-alpha production.


Assuntos
Antirreumáticos/síntese química , Ativação Linfocitária/efeitos dos fármacos , Quinazolinas/síntese química , Linfócitos T/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Animais , Antirreumáticos/farmacologia , Humanos , Camundongos , Quinazolinas/farmacologia , Relação Estrutura-Atividade
15.
Nephrol Dial Transplant ; 14(8): 1861-6, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10462263

RESUMO

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) induces nitric oxide (NO) synthesis in rat mesangial cells (MCs). We previously demonstrated that osteopontin (OP), a matrix protein that mainly interacts with the alphav integrin family, increased time-dependently by TNF-alpha stimulation at gene and protein levels. The regulation of NO synthesis by integrins or matrix proteins is unclear. METHODS: We examined whether integrin, especially alphav integrin, regulates NO synthesis in rat MCs and whether OP, an alphav integrin ligand, has an effect on TNF-alpha-induced NO synthesis. Furthermore, OP and inducible NO synthase (iNOS) gene expression was examined by Northern blotting. RESULTS: TNF-alpha increased NO synthesis in MCs in a time-dependent manner. Synthetic GRGDSP peptide, which is known to inhibit various integrins that interact with RGD-containing extracellular matrices, increased TNF-alpha-induced NO levels in a dose-dependent manner. Cyclical RGD peptide, the specific inhibitor of alphav integrin, also exhibited a dose-dependent effect of increasing NO levels, while GRGESP peptide, which has very low affinity to integrins, had no effect. In addition, NO synthesis was found to be significantly reduced when MCs were plated on OP-coated dishes compared to type I or IV collagen-coated dishes. Furthermore, anti-OP antibody increased NO synthesis in MCs. iNOS mRNA levels were increased by TNF-alpha, and were abruptly diminished after OP mRNA was significantly induced. CONCLUSIONS: The present study demonstrated the involvement of alphav integrin in TNF-alpha-induced NO synthesis in rat MCs, and the possible role of OP was suggested in the mechanism. TNF-alpha and extracellular matrices can co-operate to regulate the behaviour of MCs at least partly through NO synthesis, which may participate in the course of glomerular diseases.


Assuntos
Antígenos CD/fisiologia , Mesângio Glomerular/metabolismo , Óxido Nítrico/biossíntese , Sialoglicoproteínas/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antígenos CD/efeitos dos fármacos , Células Cultivadas , Expressão Gênica , Mesângio Glomerular/citologia , Integrina alfaV , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Oligopeptídeos/farmacologia , Osteopontina , Ratos , Ratos Sprague-Dawley , Sialoglicoproteínas/genética , Sialoglicoproteínas/farmacologia
16.
Arch Biochem Biophys ; 343(2): 181-7, 1997 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9224728

RESUMO

1alpha,25-Dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and other vitamin D3 (VD3) analogs enhanced the inhibitory effect of Activin A on murine erythroleukemia (MEL) cell proliferation and differentiation in a dose-dependent manner. 1alpha,25-(OH)2D3 inhibited differentiation more potently than proliferation by one order of magnitude. The VD3 analog study demonstrated either effect of VD3 on MEL cells via vitamin D receptor (VDR), as evidenced from the close relationship with the reported affinities for VDR. The effects of 1alpha,25-(OH)2D3 were preceded by the suppression of ornithine decarboxylase (ODC) activity, a rate-limiting enzyme in polyamine metabolism. Difluoromethylornithine (DFMO), an inhibitor of ODC, inhibited MEL cell proliferation, which was reversed by the simultaneous addition of putrescine, a product of ODC, but did not affect differentiation. 1alpha,25-(OH)2D3 inhibited cell differentiation during the phenotype-expression stage as reflected by the inhibition of beta-globin gene expression, while it inhibited proliferation in the commitment stage. Furthermore, it seems unlikely that the different effects of VD3 on proliferation and differentiation may be a result of upregulation of VDR or nongenomic action. In summary, it was suggested that 1alpha,25-(OH)2D3 inhibited Activin A-induced MEL cell proliferation and differentiation by distinct mechanisms and inhibited the proliferation by inhibiting ODC activity. We demonstrated the presence of 1alpha,25-(OH)2D3 action on leukemic cells at physiological concentration, which was distinct from the pharmacological effect of VD3 reported thus far.


Assuntos
Calcitriol/farmacologia , Diferenciação Celular/efeitos dos fármacos , Inibinas/farmacologia , Leucemia Eritroblástica Aguda/patologia , Ornitina Descarboxilase/metabolismo , Acetiltransferases/metabolismo , Ativinas , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Colecalciferol/análogos & derivados , Colecalciferol/farmacologia , Eflornitina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Globinas/biossíntese , Substâncias de Crescimento/farmacologia , Inibinas/antagonistas & inibidores , Cinética , Leucemia Eritroblástica Aguda/metabolismo , Camundongos , Inibidores da Ornitina Descarboxilase , Poliaminas/metabolismo , Proteínas Proto-Oncogênicas c-kit/biossíntese , Receptores de Calcitriol/metabolismo , Células Tumorais Cultivadas
17.
Int Clin Psychopharmacol ; 12(3): 153-7, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9248872

RESUMO

The relationship between the single oral dose pharmacokinetics of alprazolam and triazolam was studied in 10 healthy male volunteers. Each subject took single oral doses of alprazolam 0.8 mg and triazolam 0.5 mg with at least a 2 week interval between each dose. Blood samplings were performed up to 48 h after alprazolam dosing and up to 12 h after triazolam dosing. Plasma concentrations of both drugs were measured by high-performance liquid chromatography. The means +/- standard deviation of the peak plasma concentration, the total area under the plasma concentration-time curve and the elimination half-life of alprazolam were 11.3 +/- 3.1 ng/ml, 232.4 +/- 59.2 ng/h/ml and 16.5 +/- 4.6 h, respectively, and those of triazolam were 3.2 +/- 1.0 ng/ml, 11.8 +/- 5.2 ng/h/ml and 2.5 +/- 1.1 h, respectively. There was no significant correlation between the two drugs in any pharmacokinetic parameters (r = 0.35, 0.25 and 0.50). The present study thus suggests that the single oral dose pharmacokinetics of alprazolam and triazolam do not correlate well in individuals.


Assuntos
Alprazolam/farmacocinética , Ansiolíticos/farmacocinética , Moduladores GABAérgicos/farmacocinética , Triazolam/farmacocinética , Adulto , Alprazolam/administração & dosagem , Alprazolam/sangue , Ansiolíticos/administração & dosagem , Ansiolíticos/sangue , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Moduladores GABAérgicos/administração & dosagem , Meia-Vida , Humanos , Masculino , Fumar/metabolismo , Triazolam/administração & dosagem
18.
J Toxicol Sci ; 20(3): 183-93, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8667445

RESUMO

Adriamycin (ADR), an anticancer drug,was intravenously administered to Slc:SD male rats at doses of 0, 1 and 2 mg/kg once a week for 4 or 9 weeks before pairing, and the treatment period and parameters suitable for detection of male fertility disorder were examined. No adverse effects were observed on the copulation index, fertility index and spermatozoa, but testicular weights were low in the 1 and 2 mg/kg groups after 4-week treatment. In the 2 mg/kg group after 9-week treatment, 11 of 12 males had died or became moribund, and no successful pregnancies were observed. The males in the 1 and 2 mg/kg groups after 9-week treatment had decreased weights of the genital organs, an extremely decreased number of sperm and low sperm motility as well as a low implantation rate and a decreased number of live fetuses. Microscopically, the numbers of spermatogonia were decreased in the 1 and 2 mg/kg groups after 4-week treatment, whereas the numbers of even spermatozoa were diminished and genital organs showed atrophy after 9-week treatment. These results indicate that 4-week treatment before pairing is sufficient to detect effects of ADR on the testis, especially on spermatogonia, and that microscopic findings and testis weight are appropriate parameters for detection of male fertility disorders.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Infertilidade Masculina/induzido quimicamente , Animais , Antibióticos Antineoplásicos/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/patologia , Masculino , Ratos , Ratos Sprague-Dawley
19.
Metabolism ; 44(1): 47-51, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7854165

RESUMO

Glicentin has been demonstrated to be released in response to the intraluminal administration of nutrients, but its biological action remains unknown. To clarify the effect of glicentin on the endocrine function of the pancreas, the present study was performed using an in vivo local circulation system of the canine pancreas. During infusion of 0.5% solution of glucose or arginine, 100 and 400 pmol glicentin and 400 pmol glucagon were administered into the pancreaticoduodenal artery (PA) within 10 minutes at 40-minute intervals successively. During glucose infusion, blood glucose in the femoral artery did not change following administration of 100 pmol glicentin, but slightly increased following 400 pmol glicentin. Plasma insulin (immunoreactive insulin [IRI]) in the pancreaticoduodenal vein (PV) increased significantly only following infusion of 400 pmol glicentin. Plasma glucagon (immunoreactive glucagon [IRG]), measured with a specific antiserum to the C-terminal portion of glucagon, did not change following administration of 100 pmol glicentin, but was slightly elevated following 400 pmol glicentin. Plasma total IRG, measured with a nonspecific antiserum, increased promptly after administration of 100 and 400 pmol glicentin. During arginine infusion, the response of plasma IRI to glicentin was markedly exaggerated both in dosages of 100 and 400 pmol. From the present study it was concluded that human glicentin clearly increases insulin release from the canine pancreas.


Assuntos
Glucagon/farmacologia , Insulina/sangue , Fragmentos de Peptídeos/farmacologia , Precursores de Proteínas/farmacologia , Animais , Arginina/farmacologia , Cães , Relação Dose-Resposta a Droga , Glicentina , Peptídeos Semelhantes ao Glucagon , Glucose/farmacologia , Proteínas Recombinantes
20.
Auris Nasus Larynx ; 20(4): 291-5, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8172540

RESUMO

A 63-year-old male with the left parotid gland carcinoma was operated with the reconstruction of the left carotid artery after the left radical neck dissection. The greater saphenous vein was used for the vein graft between the left common carotid artery and the medial cerebral artery. Postoperatively, a temporary loss of consciousness and a half body paresis of the contralateral side occurred, but they were recovered completely in 12 hours. Postoperative angiography showed a good blood flow in the reconstructed vessel.


Assuntos
Carcinoma/patologia , Artéria Carótida Interna/efeitos da radiação , Artéria Carótida Interna/cirurgia , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Procedimentos Cirúrgicos Vasculares , Carcinoma/radioterapia , Carcinoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Glândula Parótida/efeitos da radiação , Glândula Parótida/cirurgia , Neoplasias Parotídeas/radioterapia , Neoplasias Parotídeas/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA