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1.
Gastroenterol Rep (Oxf) ; 5(4): 277-281, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28065885

RESUMEN

BACKGROUND AND AIMS: Biopsy of the ampulla of Vater may be performed to evaluate for ampullary adenomas, suspected ampullary tumors and immunohistological staining for autoimmune pancreatitis. Ampullary biopsies are commonly performed at the time of endoscopic retrograde cholangiopancreatography (ERCP). Due to the well-established complication rate following ERCP, the contribution of ampullary biopsy as a potential independent risk factor would require a controlled comparison. METHODS: A matched-pairs, case-control analysis was performed for patients undergoing ERCP with or without ampullary biopsy. The analysis involved a retrospective review of adult patients at a tertiary-care center who underwent ampullary biopsies during ERCP compared (via procedural complexity) with a matched control group who underwent ERCP without ampullary biopsies. RESULTS: Of 159 procedures involving ampullary biopsy, 54 ERCPs that met the inclusion criteria were performed with ampullary biopsy and included in the analysis cohort. This cohort was compared with 54 patients undergoing ERCP without ampullary biopsy, matched by American Society for Gastrointestinal Endoscopy (ASGE) grade of procedural complexity. There were no patients with sphincter of Oddi dysfunction. Ampullary biopsies suggested a diagnosis in 75.9% of the procedures including 12 adenomas, 5 adenocarcinomas and 1 intraductal papillary mucinous neoplasm. Including major and minor complications, the overall complication rate with biopsy (9.3%) was equivalent to the complication rate in the control group without ampullary biopsy (9.3%, P>0.99). The incidence of post-procedure pancreatitis was not significantly different between the two groups (5.6% vs 3.7%, P=0.6). Age and pancreatic duct manipulation, but not ampullary biopsy, were associated with complications on multivariate analysis in the study population. CONCLUSIONS: Ampullary biopsy performed during ERCP had a high diagnostic yield and was not associated with an increased rate of post-procedure complications or pancreatitis when compared with ERCP alone.

2.
Gastroenterology ; 146(2): 473-83.e3, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24507550

RESUMEN

BACKGROUND & AIMS: A high-fat diet (HFD) can cause serious health problems, including alteration of gastrointestinal transit, the exact mechanism of which is not clear. Several microRNAs (miRNAs) are involved in energy homeostasis, lipid metabolism, and HFD-induced weight gain. We investigated the role of miRNAs in HFD-induced damage to the enteric nervous system. METHODS: Male mice were fed a HFD (60% calories from fat) or regular diets (18% calories from fat) for 11 weeks. Mice on regular diets and HFDs were given intraperitoneal injections of Mir375 inhibitor or a negative control. Body weights, food intake, stool indices, and gastrointestinal transit (following Evans blue gavage) were measured. An enteric neuronal cell line (immorto-fetal enteric neuronal) and primary enteric neurons were used for in vitro studies. RESULTS: HFD delayed intestinal transit, which was associated with increased apoptosis and loss of colonic myenteric neurons. Mice fed a low-palmitate HFD did not develop a similar phenotype. Palmitate caused apoptosis of enteric neuronal cells associated with mitochondrial dysfunction and endoplasmic reticulum stress. Palmitate significantly increased the expression of Mir375 in vitro; transfection of cells with a Mir375 inhibitor prevented the palmitate-induced enteric neuronal cell apoptosis. Mir375 expression was increased in myenteric ganglia of mice fed HFD and associated with decreased levels of Mir375 target messenger RNAs, including Pdk1. Systemic injection of a Mir375 inhibitor for 5 weeks prevented HFD-induced delay in intestinal transit and morphologic changes. CONCLUSIONS: HFDs delay colonic transit, partly by inducing apoptosis in enteric neuronal cells. This effect is mediated by Mir375 and is associated with reduced levels of Pdk1. Mir375 might be targeted to increase survival of enteric neurons and gastrointestinal motility.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/efectos adversos , Sistema Nervioso Entérico/patología , Tránsito Gastrointestinal/fisiología , MicroARNs/metabolismo , Neuronas/patología , Palmitatos/efectos adversos , Animales , Apoptosis/fisiología , Biomarcadores/metabolismo , Línea Celular , Colon/inervación , Colon/patología , Colon/fisiopatología , Sistema Nervioso Entérico/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/administración & dosificación , MicroARNs/antagonistas & inhibidores , Neuronas/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Distribución Aleatoria , Estrés Fisiológico
3.
Mol Vis ; 16: 2328-41, 2010 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-21139982

RESUMEN

PURPOSE: Ball-and-sockets and protrusions are specialized interlocking membrane domains between lens fibers of all species studied. Ball-and-sockets and protrusions are similar in their shape, size, and surface morphology, and are traditionally believed to play a key role in maintaining fiber-to-fiber stability. Here, we evaluate the hypothesis that ball-and-sockets and protrusions possess important structural and functional differences during fiber cell differentiation and maturation. METHODS: Intact lenses of leghorn chickens (E7 days to P62 weeks old) and rhesus monkeys (1.5-20 years old) were studied with SEM, freeze-fracture TEM, freeze-fracture immunogold labeling (FRIL), and filipin cytochemistry for membrane cholesterol detection. RESULTS: SEM showed that ball-and-sockets were distributed along the long and short sides of hexagonal fiber cells, whereas protrusions were located along the cell corners, from superficial to deep cortical regions in both chicken and monkey lenses. Importantly, by freeze-fracture TEM, we discovered the selective association of gap junctions with all ball-and-sockets examined, but not with protrusions, in both species. In the embryonic chicken lens (E18), the abundant distribution of ball-and-socket gap junctions was regularly found in an approximate zone extending at least 300 µm deep from the equatorial surface of the superficial cortical fibers. Many ball-and-socket gap junctions often protruded deeply into neighboring cells. However, in the mature fibers of monkey lenses, several ball-and-sockets exhibited only partial occupancy of gap junctions with disorganized connexons, possibly due to degradation of gap junctions during fiber maturation and aging. FRIL analysis confirmed that both connexin46 (Cx46) and connexin50 (Cx50) antibodies specifically labeled ball-and-socket gap junctions, but not protrusions. Furthermore, filipin cytochemistry revealed that the ball-and-socket gap junctions contained different amounts of cholesterol (i.e., cholesterol-rich versus cholesterol-free) as seen with the filipin-cholesterol-complexes (FCC) in different cortical regions during maturation. In contrast, the protrusions contained consistently high cholesterol amounts (i.e., 402 FCCs/µm2 membrane) which were approximately two times greater than that of the cholesterol-rich gap junctions (i.e., 188 FCCs/µm2 membrane) found in ball-and-sockets. CONCLUSIONS: Gap junctions are regularly associated with all ball-and-sockets examined in metabolically active young cortical fibers, but not with protrusions, in both chicken and monkey lenses. Since these unique gap junctions often protrude deeply into neighboring cells to increase membrane surface areas, they may significantly facilitate cell-to-cell communication between young cortical fiber cells. In particular, the large number of ball-and-socket gap junctions found near the equatorial region may effectively facilitate the flow of outward current toward the equatorial surface for internal circulation of ions in the lens. In contrast, a consistent distribution of high concentrations of cholesterol in protrusions would make the protrusion membrane less deformable and would be more suitable for maintaining fiber-to-fiber stability during visual accommodation. Thus, the ball-and-sockets and protrusions are two structurally and functionally distinct membrane domains in the lens.


Asunto(s)
Extensiones de la Superficie Celular/metabolismo , Uniones Comunicantes/metabolismo , Cristalino/citología , Cristalino/metabolismo , Animales , Transporte Biológico , Extensiones de la Superficie Celular/ultraestructura , Embrión de Pollo , Pollos , Colesterol/metabolismo , Técnica de Fractura por Congelación , Haplorrinos , Cristalino/embriología , Cristalino/ultraestructura , Modelos Biológicos
4.
Skin Res Technol ; 15(2): 230-6, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19622132

RESUMEN

BACKGROUND/PURPOSE: Red fluorescence of the face induced by ultraviolet light is thought to be due to Propionibacterium acnes. However, recently there are reports correlating this red fluorescence with the amount of facial sebum secretion. This study was performed to investigate the relationship between the areas of facial red fluorescence with culture results of P. acnes and the amount of sebum secretion. METHODS: Nineteen patients with acne were included. P. acnes cultures were done on specimens obtained from areas with red fluorescence. In addition, the amount of facial sebum secretion and the skin surface pH (SSPH) were measured. Correlation analysis of these parameters and the culture results were performed with the image analysis data from the red fluorescence of the face. RESULTS: P. acnes was cultured in 36.5% of cases. The correlation of the culture rate with the red fluorescence areas was not significant. After classifying the patients into high-sebum and low-sebum groups, there was a significant difference in the red fluorescence areas. In addition, the red fluorescence area correlated with the SSPH. CONCLUSIONS: The red fluorescence area showed a stronger correlation with sebum secretion than with the presence of P. acnes. This finding suggests that the red fluorescence is affected by sebum not just P. acnes.


Asunto(s)
Acné Vulgar/metabolismo , Acné Vulgar/microbiología , Color , Microscopía Fluorescente/métodos , Fotograbar/métodos , Propionibacterium acnes/aislamiento & purificación , Sebo/fisiología , Rayos Ultravioleta , Acné Vulgar/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Masculino
5.
Arch Pharm Res ; 26(9): 739-46, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14560924

RESUMEN

Ultraviolet B (UVB) is known to induce apoptosis in human melanocytes. Here we show the cytoprotective effect of sphingosine-1-phosphate (S1P) against UVB-induced apoptosis. We also show that UVB-induced apoptosis of melanocytes is mediated by caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, and that S1P prevents apoptosis by inhibiting this apoptotic pathway. We further investigated three major mitogen-activated protein (MAP) kinases after UVB irradiation. UVB gradually activated c-Jun N-terminal kinase (JNK) and p38 MAP kinase, while extracellular signal-regulated protein kinase (ERK) was inactivated transiently. Blocking of the p38 MAP kinase pathway using SB203580 promoted cell survival and inhibited the activation of caspase-3 and PARP cleavage. These results suggest that p38 MAP kinase activation may play an important role in the UVB-induced apoptosis of human melanocytes. To explain this cytoprotective effect, we next examined whether S1P could inhibit UVB-induced JNK and p38 MAP kinase activation. However, S1P was not found to have any influence on UVB-induced JNK or p38 MAP kinase activation. In contrast, S1P clearly stimulated the phosphorylation of ERK, and the specific inhibition of the ERK pathway using PD98059 abolished the cytoprotective effect of S1P. Based on these results, we conclude that the activation of p38 MAP kinase plays an important role in UVB-induced apoptosis, and that S1P may show its cytoprotective effect through ERK activation in human melanocytes.


Asunto(s)
Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Lisofosfolípidos/farmacología , Melanocitos/efectos de los fármacos , Melanocitos/efectos de la radiación , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Esfingosina/farmacología , Rayos Ultravioleta/efectos adversos , Antracenos/farmacología , Apoptosis/fisiología , Caspasa 3 , Inhibidores de Caspasas , Caspasas/metabolismo , Caspasas/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Citoprotección/fisiología , Relación Dosis-Respuesta en la Radiación , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Activación Enzimática/efectos de la radiación , Flavonoides/farmacología , Humanos , Imidazoles/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos , Corea (Geográfico) , Lisofosfolípidos/antagonistas & inhibidores , Lisofosfolípidos/fisiología , Melanocitos/fisiología , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/efectos de la radiación , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/metabolismo , Piridinas/farmacología , Esfingosina/análogos & derivados , Esfingosina/antagonistas & inhibidores , Esfingosina/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos
6.
Cell Signal ; 15(10): 919-26, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12873705

RESUMEN

In this study, we investigated the signalling pathways induced by ultraviolet B (UVB) and the effects of sphingosine-1-phosphate on UVB-induced apoptosis of mouse melanocytes, Mel-Ab, and observed the cytoprotective effects of sphingosine-1-phosphate on UVB-induced apoptosis. Since sphingosine-1-phosphate is a well-known mitogenic agent, we thought it possible that the mitogenic effect of sphingosine-1-phosphate might contribute to cell survival. However, we found that sphingosine-1-phosphate significantly inhibits DNA synthesis. We next examined the regulation of the three major subfamilies of mitogen-activated protein (MAP) kinases and of the Akt pathway by sphingosine-1-phosphate against UVB-induced apoptosis. UVB irradiation resulted in the remarkable and sustained activation of c-Jun N-terminal kinase (JNK), while p38 MAP kinase was only transiently activated. The basal level of extracellular signal-regulated protein kinase (ERK) phosphorylation decreased 30 min after UVB irradiation, whereas the basal level of Akt phosphorylation was unaffected by UVB. We also found that sphingosine-1-phosphate potently stimulates the phosphorylation of both ERK and Akt, which are involved in the cell survival-signalling cascade. Furthermore, the specific inhibition of the ERK and Akt pathways by PD98059 and LY294002, respectively, restored the cytoprotective effect induced by sphingosine-1-phosphate. On the other hand, the p38 inhibitor SB203580 additively enhanced the cytoprotective effect on sphingosine-1-phosphate. Based on these results, we conclude that the activation of p38 MAP kinase plays an important role in UVB-induced apoptosis, and that sphingosine-1-phosphate probably exert its cytoprotective effect in Mel-Ab cells through ERK and Akt activation.


Asunto(s)
Lisofosfolípidos , Melanocitos/enzimología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas , Transducción de Señal , Esfingosina/análogos & derivados , Esfingosina/farmacología , Animales , Apoptosis , Línea Celular Tumoral , Supervivencia Celular , Citoprotección , Activación Enzimática , Melanocitos/efectos de los fármacos , Melanocitos/efectos de la radiación , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt , Sales de Tetrazolio/química , Timidina/análisis , Proteínas Quinasas p38 Activadas por Mitógenos
7.
J Cell Sci ; 116(Pt 9): 1699-706, 2003 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-12665551

RESUMEN

Sphingosine-1-phosphate (S1P) has emerged as a bioactive lipid modulator that mediates a variety of cell functions. However, the effects of S1P on melanogenesis are not well known. Therefore, we investigated the actions of S1P on melanin synthesis using a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. This study shows that S1P significantly inhibits melanin synthesis in a concentration-dependent manner, and also that the activity of tyrosinase was reduced in S1P-treated cells. In contrast, a specific extracellular signal-regulated protein kinase (ERK) pathway inhibitor, PD98059, increased tyrosinase activity and melanin production, and PD98059 also restored the S1P-induced reduction of tyrosinase activity and pigmentation. In addition, we found that S1P induces the sustained activation of ERK and the subsequent degradation of microphthalmia-associated transcription factor (MITF), which plays a key role in melanogenesis. Thus, we further studied the relationship between the ERK pathway and melanin synthesis. PD98059 was found to prevent the S1P-induced MITF phosphorylation and degradation and to abrogate the S1P-induced downregulation of tyrosinase and of tyrosinase-related protein 1 (TRP1) production. These results indicate that the ERK pathway is potently involved in the melanogenic signaling cascade, and that S1P-induced ERK activation contributes to reduced melanin synthesis via MITF degradation. Therefore, we suggest that S1P reduces melanin synthesis by ERK activation, MITF phosphorylation and degradation, and by the subsequent downregulation of tyrosinase and TRP-1 production.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Lisofosfolípidos , Melaninas/biosíntesis , Glicoproteínas de Membrana , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oxidorreductasas , Esfingosina/análogos & derivados , Esfingosina/farmacología , Factores de Transcripción/metabolismo , Animales , Secuencia de Bases , Línea Celular , ADN Complementario/genética , Proteínas de Unión al ADN/genética , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Melanocitos/efectos de los fármacos , Melanocitos/metabolismo , Ratones , Factor de Transcripción Asociado a Microftalmía , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Biosíntesis de Proteínas , Factores de Transcripción/genética
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