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1.
Gan To Kagaku Ryoho ; 40 Suppl 2: 216-8, 2013 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-24712151

RESUMEN

Discharge support, although provided for a limited time, is of vital importance in the acute phase care period. Such support is necessary to ensure continuity of care and treatment even after being discharged from the hospital. I acquired both the viewpoints of the family and the nurse of a patient who was about to be discharged from the hospital after cerebral hemorrhage. However, the patient's family and I were not able to decide on a home care plan or hospital-to-home transfer ahead of time because of the unstable condition of the patient, limited care power of the family, and varying discharge plans among the family members. I intended to help in the decision-making process, taking into consideration the patient's best interest. I evaluated the viewpoint of the family and was able to understand situations in which a family member, who assumes the role of a primary care giver, would need guidance in providing home care to the patient.


Asunto(s)
Hemorragia Cerebral/enfermería , Servicios de Atención de Salud a Domicilio , Grupo de Atención al Paciente , Alta del Paciente , Anciano , Familia , Humanos , Masculino
2.
Gan To Kagaku Ryoho ; 40 Suppl 2: 221-3, 2013 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-24712153

RESUMEN

Our nutrition support team (NST) designed the NST summary for cooperation among personnel providing medical care for nutritional management of high-need patients in our area. After the introduction of the NST fee under the health care system, the number of summary publications decreased. The requested NST fee is necessary for publication of a nutritional care plan and report upon patient discharge. We hypothesized that the nutritional care plan and discharge report were being substituted for the NST summary at the time of patient discharge. We retrospectively investigated 192 cases with NST fee. There were only 13 cases of overlapping publication, and the NST summary was necessary for 107 of 179 cases in which no NST summary had been prepared. Since the space on the report form is limited, it can provide only limited information. However, the NST summary can convey detailed supplementary information. Therefore, there is a high need for the NST summary, and publication of NST summaries for the appropriate cases must continue.


Asunto(s)
Apoyo Nutricional , Grupo de Atención al Paciente , Alta del Paciente , Informe de Investigación , Estudios Retrospectivos
3.
Gan To Kagaku Ryoho ; 39 Suppl 1: 12-4, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23268886

RESUMEN

We introduced the electronic health record system in 2002. We produced a community medical network system to consolidate all medical treatment information from the local institute in 2010. Here, we report on the present status of this system that has been in use for the previous 2 years. We obtained a private server, set up a virtual private network(VPN)in our hospital, and installed dedicated terminals to issue an electronic certificate in 50 local institutions. The local institute applies for patient agreement in the community hospital(hospital designation style). They are then entitled to access the information of the designated patient via this local network server for one year. They can access each original medical record, sorted on the basis of the medical attendant and the chief physician; a summary of hospital stay; records of medication prescription; and the results of clinical examinations. Currently, there are approximately 80 new registrations and accesses per month. Information is provided in real time allowing up to date information, helping prescribe the medical treatment at the local institute. However, this information sharing system is read-only, and there is no cooperative clinical pass system. Therefore, this system has a limit to meet the demand for cooperation with the local clinics.


Asunto(s)
Servicios de Salud Comunitaria , Registros Electrónicos de Salud/instrumentación , Hospitales Municipales , Internet/instrumentación , Redes Comunitarias , Grupo de Atención al Paciente
4.
Gan To Kagaku Ryoho ; 39 Suppl 1: 18-20, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23268888

RESUMEN

Ten years has passed since we began the nutrition support team(NST)to make a regional alliance between local institutions for construction of the NST network. The network was formed with the following aims: 1) regional joint conferences for learning about nutrition with family doctors, facilities, and hospitals; 2) open general meetings for information about nutrition within the suburbs of our city; 3) preparing and sending an NST manual about parenteral nutrition(PN)and enteral nutrition(EN); and 4) preparation of an NST summary of patient malnutrition to foster mutual understanding. We produced a questionnaire summarizing the completion of nutritional management in patients. The following positive benefits were observed: 1) improved nutritional motivation and technique; 2) reduced nutritional confusion after discharge from our hospital; and 3) lower levels of anxiety in the facilities, the patient, and among the patient's family. In addition, follow-upinquiries allowed us to estimate whether our nutritional strategy was adequate. A more widely open regional alliance is needed in the future to strengthen patient nutrition following hospital discharge.


Asunto(s)
Redes Comunitarias , Apoyo Nutricional , Grupo de Atención al Paciente , Calidad de la Atención de Salud , Factores de Tiempo
5.
Gan To Kagaku Ryoho ; 39 Suppl 1: 55-7, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23268900

RESUMEN

In collaboration between the in-hospital nutrition support team and infection control team, we attempted to standardize the management of infusion therapy. We report on a simple and effective at-home infusion therapy, after total parenteral nutrition(TPN)therapy, by using a Broviac catheter in a discharged patient with a severe skin condition. The patient was a man in his 50s who had amyloidosis. Because of dysphagia and complications of the digestive organs, TPN was chosen as the method for nutritional management. At the beginning the patient repeated infection and a trouble of the skin, but the insertion site was managed by the existing standardized manual. However, switching to a Broviac catheter improved the existing disease. Dermatopathy was improved and there was no catheter-related bloodstream infection under the new management method. Furthermore, the patient is now able to feed orally. Patients should be evaluated individually, and for the case that is hard to care with a manual, it is necessary to choose the best possible method.


Asunto(s)
Catéteres , Terapia de Infusión a Domicilio , Enfermedades de la Piel/etiología , Catéteres/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Nutrición Parenteral Total , Alta del Paciente
6.
Gan To Kagaku Ryoho ; 39 Suppl 1: 86-8, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23268909

RESUMEN

We sent the reports and plans concerning nutritional management to the 81 facilities, such as a hospital, nursing home, or clinic of home care, and carried out the questionnaire to determine their level of understanding and utilization of the reports. Sixty-nine % understood the purpose of the survey, with 74% noting that the report served as a reference. The purpose of the report was relatively well understood in the hospital or nursing home environments, but was not sufficiently understood in the clinics. In addition, it became clear that several facilities involved with one patient. Therefore, it was necessary to send a report to each facility. The interest in the report concerning nutritional management was very high in a range of various medical workers. Sections such as "matters that require attention, a characteristic in the nourishment management", "dysphagia ", and "a nourishment management method" were considered useful by these workers. The nutritional evaluation of patients discharged may be difficult; therefore, information from reports on nutritional management may help to make a more informed decision on future nutritional management.


Asunto(s)
Encuestas Nutricionales , Servicios de Atención de Salud a Domicilio , Hospitales , Humanos , Encuestas Nutricionales/estadística & datos numéricos , Alta del Paciente , Encuestas y Cuestionarios
7.
Gan To Kagaku Ryoho ; 39 Suppl 1: 95-7, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23268912

RESUMEN

In our hospital, the nutrition support team(NST)deepened relations with the local medical institution for sequential nutritional management following patient discharge. We began to process additional reports about patient nutritional management that could be passed onto any other institute for subsequent nutritional therapy. Three months following discharge, the main method of nutritional management was examined in 109 patients who were discharged between April 2008 and July 2010 and who were receiving the majority of nutrients via gastrostomy. Ten of these patients could feed orally. We choose the best methods at that time according to the patient condition, the medical treatment environment, and the patients' family. A change in those aspects following discharge will lead to a change in nutritional management methods. Observing the current nutritional therapy methods in patients after discharge is beneficial and allows us to produce a summary of this information to send to the local medical institute and to provide guidelines for the most appropriate procedures for nutritional management via gastrostomy.


Asunto(s)
Ingestión de Energía , Gastrostomía , Adulto , Anciano , Anciano de 80 o más Años , Nutrición Enteral , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Encuestas Nutricionales
8.
Rinsho Shinkeigaku ; 51(3): 215-8, 2011 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-21485169

RESUMEN

Three months prior to presentation, a 76-year-old woman suffered from insomnia and was prescribed some antidepressants and hypnotics. At that time, brain MRI showed no cerebral infarcts. Having developed an action tremor of the left hand, bradykinesia, and unstable gait, she visited our hospital. Neurological examination revealed rigidity of the neck and left limbs, clumsiness of the left hand, action tremor, and decreasing swing of the left arm while walking. 123I-metaiodobenzylguanidine scintigraphy showed no decrease of the heart/mediastinum ratio. The second MRI showed an old cerebral infarct located just in the right external segment of the globus pallidus. Since drug-induced parkinsonism was suspected, paroxetine and trazodone were discontinued, but her symptoms did not improve. We concluded that her hemiparkinsonism was due to the cerebral infarct in the right external segment of the globus pallidus, because her symptoms did not respond to dopamine agonist and L-dopa therapy, and the onset of symptoms corresponded with the time of appearance of the cerebral infarct. This is a rare case that is important for understanding the mechanism of parkinsonism.


Asunto(s)
Infarto Cerebral/complicaciones , Globo Pálido/irrigación sanguínea , Trastornos Parkinsonianos/etiología , Anciano , Femenino , Humanos
9.
Endocr J ; 57(4): 303-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20075562

RESUMEN

Oxidative stress has been implicated as a causal role in atherosclerosis, microvascular complications of diabetes as well as in beta cell failure in type 2 diabetes. PPARgamma agonists not only improve insulin sensitivity but also eliminate oxidative stress. In mouse, catalase, a major antioxidant enzyme, is directly regulated by PPARgamma through two PPARgamma binding elements in its promoter. This study examined the regulatory mechanisms of catalase expression in human. Expression of catalase was significantly upregulated in human primary adipocytes upon treatment with a PPARgamma agonist. However, the mouse PPARgamma response elements are not functionally conserved in human catalase promoter. In luciferase reporter assay containing human catalase promoter, PPARgamma /RXRalpha, in combination of a PPARgamma agonist significantly transactivated 19 kb of promoter and this was mediated via a novel PPARgamma response element (PPRE) at -12 kb from transcription initiation site of human catalase gene. Electrophoretic mobility shift assay showed direct binding of PPARgamma to this PPRE. Together, our results indicate that PPARgamma regulates the expression of catalase gene in human through a PPRE distinct from that of mouse, and could explain, at least in part, the observed inhibitory effects of PPARgamma on oxidative stress in human.


Asunto(s)
Catalasa/genética , Regulación Enzimológica de la Expresión Génica/fisiología , PPAR gamma/fisiología , Elementos de Respuesta/fisiología , Adipocitos/enzimología , Animales , Sitios de Unión , ADN/química , ADN/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Humanos , Ratones , Mutagénesis Sitio-Dirigida , Estrés Oxidativo/fisiología , PPAR gamma/agonistas , PPAR gamma/genética , Pioglitazona , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , Elementos de Respuesta/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie , Tiazolidinedionas/farmacología , Regulación hacia Arriba/efectos de los fármacos
10.
Gan To Kagaku Ryoho ; 37 Suppl 2: 221-3, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21368530

RESUMEN

Dysphagia is usually a major problem for the elderly to go home after a surgical treatment for the bone fracture of the thigh bone cervix or trochanter part in the leg. We analyzed each clinical course with regard to a change of the oral intake and the nutritional status, the activity of daily living(ADL)and a nutritional management and the place after the patient was discharged. According to our results, about 20% of the patients among those surgical cases were pointed with dysphagia, and there were many cases that ADL was ultimately gotten worse. We took care of disphagia by doing a best practice of changing in feedings and deglutition function. However, some of the patients with the problem finally moved to another elderly health care institute against their primary wishes to go home. Furthermore, 55% of the disphagia patients became dementia. It seems that dementia might be a high risk factor of disphagia. We should do more better job for managing disphargia during a peri-operative period just after admission.


Asunto(s)
Actividades Cotidianas , Trastornos de Deglución/terapia , Servicios de Atención de Salud a Domicilio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino
11.
Gan To Kagaku Ryoho ; 37 Suppl 2: 224-6, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21368531

RESUMEN

The elderly patients are susceptible to acute renal failure due to dehydration or infection. Therefore, the drug should be administered with caution. We report two cases of acute renal failure from dehydration that led to a subsequent drug poisoning. Case 1: An 85-year-old woman with a history of colorectal cancer surgery was admitted to our emergency department for appetite loss and weakness. Because she was given a normal amount of drugs under the condition of poor oral intake, she was hospitalized by digitalism. Case 2: A 72-year-old woman was admitted to our emergency department for disturbance of consciousness and appetite loss. The medication given by a staff in geriatric health services facility appeared to have caused a pilsicainide poisoning. As the elderly patients were given a normal amount of drugs under the poor oral intake condition, blood levels of renal excretion type drug had increased in both cases. Medication management for the elderly should be comprehensively considered the background of the individual.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antiarrítmicos/envenenamiento , Deshidratación/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Servicios de Atención de Salud a Domicilio , Lidocaína/análogos & derivados , Lesión Renal Aguda/etiología , Anciano , Anciano de 80 o más Años , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Femenino , Humanos , Lidocaína/envenenamiento , Lidocaína/uso terapéutico , Cuidados Paliativos , Neoplasias del Recto/terapia
12.
Gan To Kagaku Ryoho ; 37 Suppl 2: 272-4, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21368547

RESUMEN

A 6 0-year-old woman with severe obese and type-2 diabetes was hospitalized due to poorly controlled glycemia by worsening osteoarthritis of both knees. Although a diet therapy(1,200 kcal/day)was initially offered, but the body weight did not decrease. Thus, we changed VLCD therapy to LCD therapy sequentially. The weight loss made her possible not only to walk with a walker but it also improved a glycemic control. Because it was thought to be necessary to reduce her economic burden in order to continue the LCD therapy after was discharged, an inexpensive LCD menu was devised based on meal and auxiliary nutrients including trace elements. To support the LCD therapy at home, it is important to propose a simple and sustainable approach with a consideration of economic aspects as well as home environment.


Asunto(s)
Restricción Calórica , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos , Obesidad/dietoterapia , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Persona de Mediana Edad , Obesidad/complicaciones
13.
Gan To Kagaku Ryoho ; 37 Suppl 2: 278-80, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21368549

RESUMEN

We made a low calorie diet(LCD)menu which added two commercial supporting nutritional supplements to a meal. Because a conventional formula food is very expensive, the patient was not able to afford it at home. Those supplements are a total enteral formula with enriched nutrient(ACURE EN800)and vitamin-mineral rich drink(V CRESC). The contents of vitamin and mineral in this menu satisfied the dietary reference intakes, though protein was a little low. However, we could keep the price low compared to the formula food. The patient was able to switch over to home LCD therapy with the menu.


Asunto(s)
Restricción Calórica , Alimentos Formulados , Servicios de Atención de Salud a Domicilio , Grupo de Atención al Paciente , Dieta
14.
Gan To Kagaku Ryoho ; 37 Suppl 2: 281-3, 2010 12.
Artículo en Japonés | MEDLINE | ID: mdl-21368550

RESUMEN

The nutritional management of a patient discharged from a primary hospital will not end just there. The nutritional management information issued by the primary hospital is required when a patient moves to a next institute.We,the Nutritional Support Team(NST), make a nutrition summary report in addition to letters written by the doctor and the ward in charge. We investigated a total of 64 patients three months after their discharge, and followed them for a year since April 2008. On some patients, the nutritional care had to be changed in accordance with the facility and the patients' primary disease status.In order for the nutrition management to be continued, a bidirectional communication exchange between the primary hospital and acute phase hospital is essential. In other words, a seamless nutritional management for patients has to be executed. When the disease condition of the patient has changed, the host institution must consult with us about the new nutritional care to the patient. On the other hand, we should keep in touch to reduce a communication distance in the region.


Asunto(s)
Encuestas Nutricionales/estadística & datos numéricos , Grupo de Atención al Paciente , Estudios de Seguimiento , Alimentos Formulados , Alta del Paciente
15.
Am J Physiol Endocrinol Metab ; 296(6): E1326-34, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19366877

RESUMEN

Oxidative stress plays an important role in obesity-related metabolic diseases. Glutathione peroxidase (GPX) is an antioxidant enzyme downregulated in adipose tissue of obese mice. However, the role of GPX in adipocytes remains elusive. The objective of this study was to clarify the pathophysiological changes in GPX activity and glutathione metabolism and their roles in the pathogenesis of insulin resistance in adipocytes. To achieve this goal, we measured cellular GPX activity, glutathione (GSH) contents, GSH/GSSG ratio, and mRNA expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for de novo GSH synthesis, in adipose tissue of control and ob/ob mice and in 3T3-L1 adipocytes treated with insulin, H(2)O(2), free fatty acid (FFA), or TNFalpha. Furthermore, we investigated the effects of GPX inhibition with a specific GPX inhibitor or RNA interference against GPX, H(2)O(2), and reduced GSH on insulin signaling in 3T3-L1 adipocytes. ob/ob Mice showed not only a decrease in cellular activity of GPXs (GPX1, -4, and -7) but also an increase in gamma-GCS expression, resulting in increased GSH contents in adipose tissue. These alterations in glutathione metabolism were also observed during differentiation of 3T3-L1 cells and their exposure to insulin, FFA, or H(2)O(2). Inhibition of GPX activity, addition of GSH, and H(2)O(2) resulted in impaired insulin signaling in 3T3-L1 adipocytes. These results suggest that decreased GPX activity and increased gamma-GCS expression lead to overaccumulation of GSH, which might be involved in the pathogenesis of insulin resistance in obesity.


Asunto(s)
Adipocitos/enzimología , Glutatión/metabolismo , Resistencia a la Insulina/fisiología , Insulina/metabolismo , Obesidad/metabolismo , Células 3T3-L1 , Animales , Regulación hacia Abajo/fisiología , Glutamato-Cisteína Ligasa/genética , Glutamato-Cisteína Ligasa/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/fisiopatología , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/fisiología
16.
Biochem Biophys Res Commun ; 379(2): 547-52, 2009 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-19116132

RESUMEN

Obesity is associated with insulin resistance and a mild chronic inflammation in adipose tissues. Recent studies suggested that GM3 ganglioside mediates dysfunction in insulin signaling. However, it has not been determined the ganglioside profiling in adipose tissues of obese animals. Here, we for the first time examined semi-quantitative ganglioside profiles in the adipose tissues of high fat- and high sucrose-induced obese, diabetic C57BL/6J mice by TLC and HPLC/mass spectrometry. In control adipose tissues GM3 dominated with traces of GM1 and GD1a; obesity led to a dramatic increase in GM2, GM1, and GD1a with the GM3 content unchanged. Similar results were obtained in KK and KKAy mice. Adipocytes separated from stromal vascular cells including macrophages contained more of those gangliosides in KKAy mice than in KK mice. These results underscore those gangliosides in the pathophysiology of obesity-related diseases.


Asunto(s)
Tejido Adiposo/metabolismo , Gangliósidos/metabolismo , Obesidad/metabolismo , Adipocitos/metabolismo , Tejido Adiposo/química , Animales , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Gangliósido G(M2)/análisis , Gangliósido G(M2)/genética , Gangliósido G(M2)/metabolismo , Gangliósido G(M3)/análisis , Gangliósido G(M3)/genética , Gangliósido G(M3)/metabolismo , Gangliósidos/análisis , Gangliósidos/genética , Expresión Génica , Macrófagos/metabolismo , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos , N-Acetilgalactosaminiltransferasas/biosíntesis , Obesidad/complicaciones , ARN Mensajero/biosíntesis
17.
Biochem Biophys Res Commun ; 379(2): 288-92, 2009 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-19101507

RESUMEN

Rho GTPase regulates actin cytoskeleton organization and assembly in many cell types, however, its significance in adipose tissue is not well characterized. Here, we demonstrate high RhoA activity in adipose tissues of C57BL/6J mice. To determine the effect of RhoA activation on 3T3-L1 cells, stable cell lines overexpressing G14VRhoA fused to destabilizing domain of FKBP12 (DD-G14VRhoA-L1) were generated. Treatment of DD-G14VRhoA-L1 cells with Shield1 following their differentiation into adipocytes, resulted in the appearance of thick cortical actin filaments, and increased the mRNA expression levels of plasminogen activator inhibitor type-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1). The induction of PAI-1 and MCP-1 was inhibited by treatment with a Rho-associated kinase (ROCK) inhibitor, Y-27632. In 3T3-L1 adipocytes, tumor necrosis factor-alpha activated RhoA and increased mRNA expression of PAI-1 and MCP-1, and their treatment with Y-27632 partially inhibited these changes. The results indicate that RhoA-ROCK pathway induces inflammatory cytokine expression in adipocytes.


Asunto(s)
Adipocitos/enzimología , Citocinas/biosíntesis , Proteína de Unión al GTP rhoA/metabolismo , Células 3T3 , Amidas/farmacología , Animales , Quimiocina CCL2/biosíntesis , Masculino , Ratones , Ratones Endogámicos C57BL , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Serpina E2 , Serpinas/biosíntesis , Factor de Necrosis Tumoral alfa/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidores , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/antagonistas & inhibidores
18.
J Endocrinol ; 200(1): 107-16, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18931025

RESUMEN

Adiponectin is exclusively expressed in adipose tissue and secreted from adipocytes, and shows anti-diabetic and anti-atherogenic properties. However, the precise transcriptional mechanism of adiponectin remains elusive. In this study, the 5' flanking promoter region of human adiponectin gene was analyzed using UCSC genome browser, and a 10 390-bp fragment, containing an evolutionally conserved region among species, was investigated. The luciferase reporter assay using this fragment identified a novel distal enhancer of human adiponectin gene. Promoter constructs with the distal enhancer exhibited high promoter activities in 3T3-L1 mature adipocytes. However, no such activity was observed in other types of cell lines. The distal enhancer is highly conserved, and contains two completely conserved CCAAT boxes. In 3T3-L1 mature adipocytes, deletion or each point mutation of these CCAAT boxes markedly reduced luciferase activity driven by adiponectin promoter. Knockdown of CCAAT/enhancer-binding protein alpha (CEBPA; also known as C/EBPalpha) using small interfering RNA diminished adiponectin mRNA expression and luciferase activity driven by adiponectin promoter with the distal enhancer. However, adiponectin promoter with each mutation of two CCAAT boxes in the distal enhancer did not respond to knockdown of CEBPA expression. Furthermore, CEBPA bound to the distal enhancer both in vitro and in vivo. We also identified a proximal promoter region responsible for transcriptional activation by the distal enhancer in human adiponectin gene. Our results indicate that CEBPA plays a pivotal role in the transcription of human adiponectin gene via the distal enhancer and proximal region in its promoter.


Asunto(s)
Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Elementos de Facilitación Genéticos , Regulación de la Expresión Génica , Células 3T3 , Adipocitos/química , Adipocitos/metabolismo , Adiponectina/química , Adiponectina/genética , Adiponectina/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Proteínas Potenciadoras de Unión a CCAAT/genética , Genes Reporteros , Humanos , Ratones , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Unión Proteica , Alineación de Secuencia , Transcripción Genética
19.
Arterioscler Thromb Vasc Biol ; 28(5): 871-7, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18323514

RESUMEN

OBJECTIVE: Macrophage-mediated chronic inflammation of adipose tissue is causally linked to insulin resistance in obesity. The beneficial effects of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors (statins) on glucose metabolism have been suggested, but the effects of these agents on adipose tissue inflammation are unclear. The aim of the present study is to define the effects of statins on adipose tissue inflammation and macrophages. METHODS AND RESULTS: Pravastatin or pitavastatin treatment of obese mice attenuated an increase in mRNA expressions of proinflammatory genes, including MCP1 and IL6, in adipose tissue. The supernatant of TLR4-stimulated RAW264 macrophages strongly induced the expression of these genes in 3T3-L1 adipocytes, which was inhibited by pretreatment of macrophages with either statin. Statins inhibited TLR4-mediated activation of interferon (IFN) regulatory factor (IRF)3 by either lipopolysaccharide (LPS) or palmitic acid, resulting in suppression of IFN-beta expression, but not that of NF-kappaB or JNK. Moreover, statins strongly downregulated TLR3-mediated gene expressions by poly(I:C), but not TLR2-stimulation by zymosan A. Neutralization of IFN-beta attenuated proinflammatory activities of the macrophage supernatant. CONCLUSIONS: Statins partially attenuated the development of adipose tissue inflammation in obese mice, which might be associated with an inhibitory effect of statins on TLR4-triggered expression of IFN-beta via MyD88-independent signaling pathway in macrophages.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inflamación/prevención & control , Factor 3 Regulador del Interferón/metabolismo , Interferón beta/metabolismo , Macrófagos/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Células 3T3-L1 , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Femenino , Inflamación/metabolismo , Inflamación/patología , Factor 3 Regulador del Interferón/efectos de los fármacos , Interferón beta/efectos de los fármacos , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Ratones , Ratones Obesos , Factor 88 de Diferenciación Mieloide/efectos de los fármacos , Obesidad/metabolismo , Obesidad/patología , Pravastatina/farmacología , Quinolinas/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Receptor Toll-Like 4/metabolismo
20.
Biochem Biophys Res Commun ; 366(3): 698-704, 2008 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-18073138

RESUMEN

In adipose tissue of obese mice, the expression of catalase, an anti-oxidant enzyme, significantly decreases, which may cause insufficient elimination of hydrogen peroxide, but it does not in liver or skeletal muscle. However, the precise regulatory mechanism of catalase expression in adipocytes has not been fully defined. Here, we demonstrated that adipose tissues highly expressed catalase on the level comparable to liver and kidney, and treatment of mice with PPARgamma agonist significantly enhanced catalase expression in adipose tissue but not in liver. In 3T3-L1 cells, mRNA expression of catalase was up-regulated by the induction for adipose differentiation, and down-regulated by TNFalpha, in parallel with alterations in PPARgamma expression. PPARgamma agonist significantly enhanced catalase mRNA and activity. Furthermore, we newly identified a remote enhancer region containing two functional PPARgamma binding sites in mouse catalase gene. Collectively, our findings suggest that PPARgamma plays a crucial role in the expression of catalase in adipocytes.


Asunto(s)
Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Obesidad/metabolismo , PPAR gamma/metabolismo , Células 3T3-L1 , Animales , Activación Enzimática , Femenino , Regulación de la Expresión Génica , Masculino , Ratones , Especificidad de Órganos , Distribución Tisular
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