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1.
Intern Med ; 60(6): 855-858, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33087672

RESUMEN

A 58-year-old woman presented to our hospital with complaints of dysphagia. Esophagogastroduodenoscopy showed an esophagogastric junction tumor with multiple duodenal intramural metastases, and computed tomography showed peritoneal metastasis. In the middle of her fourth cycle of chemotherapy, she displayed symptoms of a left-sided multi-cranial nerve palsy. She was diagnosed with Garcin syndrome caused by meningeal carcinomatosis from gastric cancer based on the results of gadolinium-enhanced brain magnetic resonance imaging and cytology of the cerebrospinal fluid. It is important not to overlook meningeal irritation symptoms or paralysis of cranial nerves and to consider the possibility of Garcin syndrome caused by meningeal carcinomatosis.


Asunto(s)
Enfermedades de los Nervios Craneales , Carcinomatosis Meníngea , Neoplasias Meníngeas , Neoplasias Gástricas , Femenino , Humanos , Imagen por Resonancia Magnética , Carcinomatosis Meníngea/complicaciones , Carcinomatosis Meníngea/diagnóstico , Persona de Mediana Edad , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnóstico , Tomografía Computarizada por Rayos X
2.
Nihon Shokakibyo Gakkai Zasshi ; 115(2): 184-194, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-29459562

RESUMEN

Since the introduction of direct-acting antiviral (DAA)-based combination therapies in September 2014 for patients with chronic hepatitis-C (CH-C), numerous patients have been diagnosed with hepatitis-C virus (HCV)-associated hepatocellular carcinomas (HCCs) during the screening performed prior to DAA therapy. The present study was conducted on the antiviral therapy for CH-C in two phases:i) the interferon (IFN) phase between January 2011 and August 2014 and ii) the DAA phase between September 2014 and September 2016. During the DAA phase, HCCs were detected in eight patients who were referred to our hospital for anti-HCV therapy. In contrast, HCCs were detected in only two patients during the IFN phase. The number of patients with newly detected HCC in the DAA phase (20.5%) who were referred for the anti-HCV therapy was significantly higher than that in the IFN phase (1.7%). Owing to the high efficacy and safety of the DAA therapy, the number of patients referred to our hospital for anti-HCV therapy increased from 40.5 persons/year in the IFN phase to 80.3 persons/year in the DAA phase. The average ages of patients in the DAA and IFN phases were 68 and 61 years, respectively. The increase in the number of patients with newly detected HCC referred for the anti-HCV therapy in the DAA phase could be attributed to the increase in the number of referred patients for anti-HCV therapy and the aging of these patients in the DAA phase. All the eight patients with newly detected HCC who were referred for anti-HCV therapy in the DAA phase received curative treatments. The median age, rate of liver cirrhosis, and median tumor size of the patients were 69 years, 13%, and 16mm. Therefore, the findings of this study indicate that DAA therapies not only eradicate HCV infection but also contribute to the early diagnosis of HCC by encouraging the HCV-infected patients to visit hospitals and by promoting active network between hepatologists and family physicians.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/virología , Quimioterapia Combinada/métodos , Hepacivirus , Hepatitis C Crónica , Hepatitis C/tratamiento farmacológico , Neoplasias Hepáticas/virología , Anciano , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/terapia , Estudios Retrospectivos
3.
Intern Med ; 57(3): 351-355, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29093393

RESUMEN

An 85-year-old woman underwent endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice. Selective bile duct cannulation was unsuccessful because of periampullary diverticula (PAD). A pancreatic spontaneous dislodgement stent (PSDS) (5F diameter, 3 cm, straight type) was inserted to prevent post-ERCP pancreatitis. Three days after ERCP, she complained of abdominal pain, and computed tomography revealed retroperitoneal perforation because of PSDS migration to the PAD. If the papillary orifice is observed at the diverticular rim or in the diverticula, a pigtailed PSDS on the duodenal side or flanged stent on the pancreatic ductal side should be inserted in order to prevent this rare adverse event.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Divertículo/cirugía , Ictericia Obstructiva/diagnóstico por imagen , Ictericia Obstructiva/cirugía , Peritoneo/lesiones , Peritoneo/cirugía , Stents/efectos adversos , Anciano de 80 o más Años , Femenino , Humanos , Peritoneo/diagnóstico por imagen , Resultado del Tratamiento
4.
Gan To Kagaku Ryoho ; 39(13): 2541-4, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23235175

RESUMEN

A 74-year-old man was referred to our hospital because of abdominal distension. Upper gastrointestinal endoscopy revealed advanced gastric cancer and early gastric cancer. HER2-positive and AFP-producing gastric cancer with peritonitis carcinomatosa showing no indication for operation was diagnosed by histopathological and radiological examinations. He was treated with trastuzumab, docetaxel, and S-1 combination chemotherapy. At the end of the second course of therapy, the primary lesion was remarkably decreased in size and was associated with a significant decrease in serum AFP level. No serious adverse events occurred except for grade 3-4 leukopenia and neutropenia. We carried out eight courses of chemotherapy. Trastuzumab, docetaxel, and S-1 combination chemotherapy promise to be one of the effective treatments for HER2-positive and AFP-producing gastric cancer that have no indication for radical cure excision.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Docetaxel , Combinación de Medicamentos , Humanos , Masculino , Ácido Oxónico/administración & dosificación , Receptor ErbB-2/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/metabolismo , Taxoides/administración & dosificación , Tegafur/administración & dosificación , Trastuzumab , alfa-Fetoproteínas/biosíntesis
5.
Acta Otolaryngol ; 132(9): 1013-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22779447

RESUMEN

CONCLUSION: Severity of ipsilateral facial palsy (UFP) can be assessed objectively by use of OKAO Vision®. Facial symmetry percentage (FSP) values were well correlated with the results by two conventional grading systems. OBJECTIVES: To introduce the basic principle of facial motion analysis using OKAO Vision®, to represent the data measured in patients with UFP, and to show the correlation between the severity of facial palsy assessed by this method and conventional systems. METHODS: Two independent facial motions, closing the eyes and grinning, were recorded with a video camera. By comparing the movement distances between right and left sides, the eye symmetry ratio (ESR) and grin symmetry ratio (GSR) were obtained. The degree of UFP was assessed by FSP, which was calculated by the formula: FSP = (ESR + GSR)/2 × 100 (%). FSP was measured in 12 normal volunteers and in 30 patients with UFP. RESULTS: In patients with UFP, varying degrees of FSP were noted corresponding to the grade of facial palsy. The severity of facial palsy assessed by FSP was closely correlated with the Yanagihara score (r = 0.88, p < 0.05) and was inversely related to the House-Brackmann grade (r = -0.90, p < 0.05).


Asunto(s)
Diagnóstico por Computador , Parálisis Facial/diagnóstico , Procesamiento de Imagen Asistido por Computador , Programas Informáticos , Adulto , Anciano , Anciano de 80 o más Años , Asimetría Facial/clasificación , Asimetría Facial/diagnóstico , Expresión Facial , Parálisis Facial/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia
6.
Acta Otolaryngol ; 132(7): 783-7, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22668131

RESUMEN

CONCLUSION: Gene analysis of facial muscle may be a promising way to detect denervation of facial muscle, helping to determine the prognosis of a facial palsy early in its progression. OBJECTIVES: In the treatment of intratemporal facial palsy, early diagnosis of neural damage is important in deciding about therapeutic modalities. In this study, we investigated the relationship between the severity of facial palsy and the level of myogenin expressed in the facial muscle. METHODS: The animals were divided into two groups, depending on whether the facial nerve was resected or compressed. Expression of myogenin mRNA was examined using real-time PCR and in situ hybridization of the facial muscle following the nerve damage. RESULTS: Increased expression of myogenin was observed in the nerve resection group, while no such increase was seen in the nerve compression group. In situ hybridization indicated that myogenin was expressed exclusively in satellite cells around the denervated muscle fibers.


Asunto(s)
Músculos Faciales/metabolismo , Traumatismos del Nervio Facial/metabolismo , Parálisis Facial/etiología , Parálisis Facial/metabolismo , Miogenina/metabolismo , ARN Mensajero/metabolismo , Animales , Modelos Animales de Enfermedad , Traumatismos del Nervio Facial/diagnóstico , Traumatismos del Nervio Facial/etiología , Estudios de Factibilidad , Masculino , Desnervación Muscular , Miogenina/genética , Síndromes de Compresión Nerviosa , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa
7.
Cell Biol Int ; 35(4): 359-63, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21231917

RESUMEN

Fucci (fluorescent ubiquitination-based cell cycle indicator) is able to visualize dynamics of cell cycle progression in live cells; G1- and S-/G2-/M-phase cells expressing Fucci emit red and green fluorescence, respectively. This system could be applied to cell kinetic analysis of tumour cells in the field of cancer therapy; however, it is still unclear how fluorescence kinetics change after various treatments, including exposure to anticancer agents. To explore this, we arrested live HeLa cells expressing the Fucci probes at various cell cycle stages and observed the fluorescence, in conjunction with flow cytometric analysis. X-irradiation, HU (hydroxyurea) and nocodazole arrest cells at G2/M boundary, early S-phase and early M-phase, respectively. Although X-irradiation and HU treatment induced similar accumulation kinetics of green fluorescent cells, nocodazole treatment induced an abnormal red fluorescence at M phase, followed by accumulation of both red and green fluorescent cells with 4N DNA content. We conclude that certain agents that disrupt normal cell cycle regulation could cause unexpected fluorescence kinetics in the Fucci system.


Asunto(s)
Ciclo Celular/efectos de los fármacos , Colorantes Fluorescentes/análisis , Células HeLa/citología , Proteínas/análisis , División Celular/efectos de los fármacos , Supervivencia Celular , Citometría de Flujo , Fluorescencia , Fase G1/efectos de los fármacos , Fase G2/efectos de los fármacos , Expresión Génica , Células HeLa/efectos de los fármacos , Células HeLa/metabolismo , Humanos , Indicadores y Reactivos , Microscopía Fluorescente , Proteínas/genética , Ubiquitinación
8.
Eur J Pharmacol ; 612(1-3): 106-14, 2009 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-19356735

RESUMEN

Recombinant human erythropoietin (rHuEPO), which has been used clinically for the management of renal anemia, is reported to exert pleiotropic beneficial properties against acute ischemic/reperfusion injury in various tissues. To investigate the hypothesis that chronic treatment with rHuEPO might ameliorate diabetic nephropathy beyond hematopoiesis, rHuEPO (150 U/kg, subcutaneously) was administered three times per week to the streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, intravenously) significantly increased urinary protein excretion and collagen deposition in glomerular and tubulointerstitial areas in the kidney, which were attenuated by rHuEPO. rHuEPO normalized the levels of creatinine clearance, serum creatinine, and blood urea nitrogen of diabetic rats. RT-PCR analysis revealed that the expressions of mRNA for transforming growth factor-beta, osteopontin and adhesion molecules were enhanced in the diabetic rat kidney and that the overexpression of these molecules was suppressed by rHuEPO. rHuEPO exerted antioxidant properties by inhibiting renal activation and overexpression of NADPH oxidase. We found the activation of the Akt signaling pathway by the increased expression of phosphorylated Akt and GSK-3beta and a reduction of TUNEL-positive apoptotic cell death in renal tissue from rHuEPO-treated diabetic group. We also demonstrated that rHuEPO restored the endothelial nitric oxide synthase (eNOS) content in the diabetic rat kidney. On the other hand, treatment with rHuEPO did not affect blood glucose level, blood pressure, or hematocrit in diabetic rats. These results suggest that chronic treatment with rHuEPO attenuated renal injury beyond hematopoiesis and regulated apoptosis and eNOS expression, which might be due to the activation of Akt pathway.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Hematopoyesis/efectos de los fármacos , Riñón/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Glucemia/análisis , Nitrógeno de la Urea Sanguínea , Muerte Celular/efectos de los fármacos , Creatinina/sangre , Creatinina/metabolismo , Diabetes Mellitus Experimental/sangre , Eritropoyetina/genética , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Hematócrito , Humanos , Etiquetado Corte-Fin in Situ/métodos , Riñón/metabolismo , Masculino , NADPH Oxidasas/metabolismo , Osteopontina/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Proteínas Recombinantes , Transducción de Señal/efectos de los fármacos , Estreptozocina/farmacología , Factor de Crecimiento Transformador beta/metabolismo
9.
Expert Opin Pharmacother ; 9(14): 2531-6, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18778190

RESUMEN

Despite recent evidence suggesting that Bell's palsy is associated with reactivation of alfa-herpes viruses, the disease has been treated empirically, and the use of valacyclovir has not been definitively established. In 2007, two prospective, randomised, placebo-controlled trials evaluating valacyclovir were reported in patients with Bell's palsy. One demonstrated that valacyclovir/prednisolone therapy was statistically more effective than placebo/prednisolone therapy in improving the recovery of patients with Bell's palsy, excluding zoster sine herpete. However, considering the cost-benefit ratio of this treatment and the limitations of virological diagnoses, we recommend that valacyclovir should be used in cases of severe palsy within 3 days after the onset of Bell's palsy.


Asunto(s)
Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Parálisis de Bell/tratamiento farmacológico , Herpes Zóster/tratamiento farmacológico , Prednisolona/uso terapéutico , Valina/análogos & derivados , Aciclovir/administración & dosificación , Aciclovir/farmacocinética , Aciclovir/uso terapéutico , Antivirales/administración & dosificación , Antivirales/farmacocinética , Análisis Costo-Beneficio , Quimioterapia Combinada , Humanos , Prednisolona/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Valaciclovir , Valina/administración & dosificación , Valina/farmacocinética , Valina/uso terapéutico
10.
J Infect Dis ; 197(12): 1752-61, 2008 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-18442334

RESUMEN

BACKGROUND: The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type. METHODS: Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR. RESULTS: Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P < .001). H. pylori-infected patients displaying IL18 -607C/C and -137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure. CONCLUSION: H. pylori infection induces IL-18 in the gastric mucosa. H. pylori-infected patients with IL18 -607C/C and -137G/G have higher IL-18 levels, which causes severe gastric inflammation. IL18 genotype might be a marker for predicting the effects of eradication therapy.


Asunto(s)
Mucosa Gástrica/microbiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Interleucina-18/genética , Interleucina-18/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Úlcera Duodenal/genética , Úlcera Duodenal/microbiología , Dispepsia/genética , Dispepsia/microbiología , Femenino , Mucosa Gástrica/inmunología , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Úlcera Gástrica/genética , Úlcera Gástrica/microbiología
11.
Eur J Pharmacol ; 549(1-3): 124-32, 2006 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-16979161

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) are expressed on vascular tissue. To investigate the direct vasoprotective effects of PPARgamma and PPARalpha ligands, pioglitazone (3 mg/kg/day) and bezafibrate (10 mg/kg/day) were given by gavage to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.p.) significantly increased NADPH oxidase, vascular call adhesion molecule-1 (VCAM-1), and osteopontin mRNA levels in the aorta, as determined by reverse transcription (RT)-polymerase chain reaction (PCR). Immunohistochemical analysis revealed that the expression of osteopontin protein was also enhanced in the streptozotocin-injected rat aorta. Pioglitazone or bezafibrate attenuated the streptozotocin-induced increase in the expression of NADPH oxidase and VCAM-1 mRNA. The enhanced expression of osteopontin gene and protein induced by streptozotocin was suppressed by pioglitazone, whereas treatment with bezafibrate had no effect on the expression of osteopontin. We also demonstrated that pioglitazone or bezafibrate prevented the streptozotocin-induced increase in angiotensin converting enzyme (ACE) gene and protein content, by the means of RT-PCR and Western blotting. On the other hand, the treatment of pioglitazone or bezafibrate in the present study did not affect glucose tolerance, serum insulin or lipid level in streptozotocin-induced diabetic rats. These results suggest that the direct anti-oxidant and anti-inflammatory effects of PPARs ligands in the aorta of streptozotocin-induced diabetic rats were not likely to have been mediated by the normalization of glucose or lipid metabolism, but instead these salutary effects appear to have been associated with the inhibition of the expression of ACE. In addition, pioglitazone appeared to be more effective on the suppression of osteopontin expression compared with bezafibrate.


Asunto(s)
Aorta Torácica/efectos de los fármacos , Bezafibrato/farmacología , Diabetes Mellitus Experimental/prevención & control , Peptidil-Dipeptidasa A/genética , Tiazolidinedionas/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Aorta Torácica/metabolismo , Bezafibrato/administración & dosificación , Glucemia/metabolismo , Western Blotting , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Expresión Génica/genética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Hipolipemiantes/administración & dosificación , Hipolipemiantes/farmacología , Inyecciones Intraperitoneales , Insulina/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , NADPH Oxidasa 4 , NADPH Oxidasas/genética , Osteopontina/genética , Osteopontina/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Receptores Activados del Proliferador del Peroxisoma/agonistas , Pioglitazona , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tiazolidinedionas/administración & dosificación , Molécula 1 de Adhesión Celular Vascular/genética
12.
Hypertens Res ; 29(2): 105-16, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16755144

RESUMEN

Calcium channel blockers have been shown to limit the progression of atherosclerosis and decrease the incidence of cardiovascular events. To investigate vasoprotective effects beyond the blood pressure-lowering effects of these agents, amlodipine (10(-6) mol/) and manidipine (10(-6) mol/l) were used to pretreat angiotensin (Ang) II-stimulated rat cultured aortic endothelial cells. A 3-h period of Ang II treatment enhanced superoxide generation and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein, as detected by dihydroethidium staining and Western blotting, respectively. Pretreatment with amlodipine or manidipine attenuated the increased production of superoxide and the overexpression of NADPH oxidase. The enhanced expression of heme oxygenase-1 (HO-1) mRNA induced by Ang II was further increased by amlodipine, whereas pretreatment with manidipine led to a reduction in the expression of HO-1. Furthermore, Ang II increased vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) mRNA levels, as determined by reverse transcription (RT)-polymerase chain reaction (PCR). Pretreatment with either amlodipine or manidipine decreased the overexpression of VCAM-1, ICAM-1, and MCP-1. We also demonstrated that amlodipine or manidipine prevented the Ang II-induced increase in lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) content, thereby restoring control levels. These observations showed that amlodipine and manidipine reduced superoxide generation by the inhibition of the overexpression of NADPH oxidase in Ang II-stimulated endothelial cells. Such antioxidant effects of these agents might in turn have led to a decrease in the expression of VCAM-1, ICAM-1 and MCP-1. The salutary effects of calcium channel blockers in atherogenesis include the inhibition of the expression of LOX-1.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Receptores Depuradores de Clase E/efectos de los fármacos , Angiotensina II , Animales , Aorta/citología , Moléculas de Adhesión Celular/efectos de los fármacos , Células Cultivadas , Quimiocina CCL2/efectos de los fármacos , Hemo-Oxigenasa 1/efectos de los fármacos , Inflamación/metabolismo , Masculino , NADPH Oxidasas/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , Ratas , Ratas Wistar , Superóxidos/metabolismo
13.
Clin Exp Pharmacol Physiol ; 33(5-6): 440-7, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16700876

RESUMEN

1. Hyperinsulinaemia has been reported to be an independent risk factor for cardiovascular diseases. Insulin stimulates both the phosphatidylinositol 3-kinase (PI3-K)/Akt and mitogen-activated protein kinase (MAPK) pathways. To investigate the direct effects of insulin on vascular tissues, we examined the gene and protein expression of insulin signalling molecules, endothelial nitric oxide synthase (eNOS) and MAPK in aortas obtained from established hyperinsulinaemic rats under deep urethane anaesthesia (1.2 g/kg, i.p.). 2. High plasma insulin levels significantly enhanced the gene and protein expression of eNOS in aortas. This was accompanied not only by increased mRNA levels of insulin receptor substrate (IRS)-1, IRS-2, PI3-K and Akt, but also by a high protein content of Akt and phospho-Akt (Ser473). 3. In contrast, MAPK mRNA levels were decreased in hyperinsulinaemic rats compared with normoinsulinaemic rats. 4. Insulin receptor mRNA levels were also lower in insulin-treated rats rather than controls. The overexpression of mRNA for vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-I receptor was also observed in aortas from hyperinsulinaemic rats. 5. To our knowledge, these data provide the first direct measurements of the mRNA of insulin signalling molecules and the downstream eNOS and MAPK. We conclude that hyperinsulinaemia itself can lead to the upregulation of eNOS and the PI3-K/Akt pathway in the vasculature and may also induce the overexpression of VEGF and IGF-I receptor genes.


Asunto(s)
Aorta Torácica/enzimología , Regulación de la Expresión Génica , Hiperinsulinismo/enzimología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Aorta Torácica/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hiperinsulinismo/inducido químicamente , Hiperinsulinismo/genética , Hipoglucemiantes/toxicidad , Insulina/toxicidad , Proteínas Sustrato del Receptor de Insulina , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
14.
Gastroenterology ; 123(6): 1992-2004, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12454856

RESUMEN

BACKGROUND & AIMS: Mouse models of Helicobacter pylori infection have yielded variable results with respect to colonization and inflammation. We examined whether outer membrane proteins (OMPs) or the cag pathogenicity island (PAI) was responsible for some of this variability. METHODS: C57BL/6 mice received clinical H. pylori isolates with different genotypes for the cag PAI and OMP gene switch status, as well as isogenic gene knockout mutants for cagE, oipA, babA2, hopZ, cagE/oipA, or oipA/hopZ. Bacterial density, histology, and mucosal cytokine/chemokine levels were measured after 4 and 12 weeks. RESULTS: oipA, hopZ, hopO, and hopP switch status influenced both H. pylori density and colonization ability in mice. When 2 or more of the genes were "off," colonization rates were markedly reduced compared with those for strains with all genes "on" (from 58% to 0% after 12 weeks). oipA knockout mutants caused reduced inflammation and decreased mucosal interleukin 6 messenger RNA and KC messenger RNA and protein levels. H. pylori density and colonization ability were reduced if hopO or hopP switch status was changed from "on" to "off." There was a close relationship (r > 0.7) between the H. pylori density of the gastric mucosa of humans and mice when using the same H. pylori strains. CONCLUSIONS: Many of the differences reported with mouse models may reflect subtle unrecognized differences (e.g., switch status of an OMP gene), emphasizing the necessity of characterizing isolates before and after experiments. The mouse model may be suitable for investigating factors related to colonization ability, H. pylori density, and gastric mucosal inflammation.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/fisiología , Gastritis/microbiología , Gastritis/fisiopatología , Infecciones por Helicobacter/fisiopatología , Helicobacter pylori , Células Madre/fisiología , Animales , Proteínas de la Membrana Bacteriana Externa/genética , Quimiocina CXCL1 , Quimiocinas/genética , Quimiocinas CXC , Recuento de Colonia Microbiana , Citocinas/biosíntesis , Citocinas/genética , Mucosa Gástrica/metabolismo , Genoma , Genotipo , Helicobacter pylori/genética , Helicobacter pylori/fisiología , Humanos , Interleucina-6/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación/fisiología , Fenotipo , ARN Mensajero/metabolismo , Índice de Severidad de la Enfermedad
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