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1.
Eur Spine J ; 32(10): 3575-3582, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37624437

RESUMO

PURPOSE: This study aimed to investigate the recent 10-year trends in cervical laminoplasty and 30-day postoperative complications. METHODS: This retrospective multi-institutional cohort study enrolled patients who underwent laminoplasty for cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament. The primary outcome was the occurrence of all-cause 30-day complications. Trends were investigated and compared in the early (2008-2012) and late (2013-2017) periods. RESULTS: Among 1095 patients (mean age, 66 years; 762 [70%] male), 542 and 553 patients were treated in the early and late periods, respectively. In the late period, patients were older at surgery (65 years vs. 68 years), there were more males (66% vs. 73%), and open-door laminoplasty (50% vs. 69%) was the preferred procedure, while %CSM (77% vs. 78%) and the perioperative JOA scores were similar to the early period. During the study period, the rate of preservation of the posterior muscle-ligament complex attached to the C2/C7-spinous process (C2, 89% vs. 93%; C7, 62% vs. 85%) increased and the number of laminoplasty levels (3.7 vs. 3.1) decreased. While the 30-day complication rate remained stable (3.9% vs. 3.4%), C5 palsy tended to decrease (2.4% vs. 0.9%, P = 0.059); superficial SSI increased significantly (0% vs. 1.3%, P = 0.015), while the decreased incidence of deep SSI did not reach statistical significance (0.6% vs. 0.2%). CONCLUSIONS: From 2008 to 2017, there were trends toward increasing age at surgery and surgeons' preference for refined open-door laminoplasty. The 30-day complication rate remained stable, but the C5 palsy rate halved.


Assuntos
Laminoplastia , Doenças da Medula Espinal , Osteofitose Vertebral , Humanos , Masculino , Idoso , Feminino , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento , Laminoplastia/efeitos adversos , Laminoplastia/métodos , Doenças da Medula Espinal/cirurgia , Vértebras Cervicais/cirurgia , Complicações Pós-Operatórias/etiologia , Paralisia/etiologia , Osteofitose Vertebral/cirurgia
2.
J Clin Biochem Nutr ; 72(1): 61-67, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36777082

RESUMO

Fructose is associated with hyperuricemia and gout development. Focusing on fructose and fructose-containing disaccharides, we investigated the effects of three different types of carbohydrates (fructose, sucrose, and isomaltulose) on uric acid metabolism and gene expression profiling in peripheral white blood cells. In a randomized crossover study, ten healthy participants ingested test drinks of fructose, sucrose, and isomaltulose, each containing 25 g of fructose. Plasma glucose, serum and urine uric acid, and xanthine/hypoxanthine concentrations were measured. Microarray analysis in peripheral white blood cells and real-time reverse transcription polymerase chain reaction were examined at 0 and 120 in after the intake of test drinks. Serum uric acid concentrations for group fructose were significantly higher than group sucrose at 30-120 min and were significantly higher than those for group isomaltulose at 30-240 min. Several genes involved in the "nuclear factor-kappa B signaling pathway" were markedly changed in group fructose. No significant differences in the mRNA expression levels of tumor necrosis factor, nuclear factor-kappa B, interleukin-1ß, and interleukin-18 were noted. This study indicated that fructose intake (monosaccharide) elevated serum uric acid concentrations compared with disaccharide intake. Differences in the quality of carbohydrates might reduce the rapid increase of postprandial serum uric acid concentrations.

3.
Nutrition ; 85: 111128, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33545542

RESUMO

OBJECTIVES: There is substantial interest in using dark chocolate to prevent postprandial hyperglycemia. We investigated the effects of cacao polyphenol-rich chocolate on postprandial glycemic and insulinemic responses and whether cacao polyphenol-rich chocolate increases glucagon-like peptide-1 (GLP-1) secretion. METHODS: In a stratified, randomized, crossover study, 48 healthy participants ingested either water (W) or cacao polyphenol-rich chocolate plus water (C) 15 min before a 50 g oral glucose tolerance test (OGTT). Pre- and postprandial concentrations of blood glucose, insulin, free fatty acid, glucagon, and GLP-1 were evaluated. RESULTS: Peak plasma glucose concentrations did not differ significantly between groups W and C; however, plasma glucose concentrations at 120 min in group C were significantly lower than those in group W (P < .01). Postprandial serum insulin and plasma GLP-1 concentrations and incremental serum insulin and plasma GLP-1 area under the curve (AUC)-15-180 min for group C were significantly higher than those for group W (P < .05). When comparing the changes after the OGTT, the incremental plasma glucose AUC0-180 min for group C was significantly lower than that for group W (P < .05), but the incremental serum insulin and plasma GLP-1 AUC0-180 min did not differ significantly between groups W and C. CONCLUSIONS: This study indicated that the intake of cacao polyphenol-rich chocolate before a 50 g OGTT could enhance early insulin and GLP-1 secretion in healthy participants, and illustrates the potential of cacao polyphenol-rich chocolate in managing postprandial glucose excursions.


Assuntos
Cacau , Chocolate , Glicemia , Estudos Cross-Over , Polipeptídeo Inibidor Gástrico , Voluntários Saudáveis , Humanos , Incretinas , Insulina , Polifenóis , Período Pós-Prandial
4.
Nutrition ; 72: 110694, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007805

RESUMO

OBJECTIVE: The ratio of dietary carbohydrate to fat may affect phosphorus metabolism because both calcium and phosphorus are regulated by similar metabolic mechanisms, and a high-fat diet (HFD) induces deleterious effects on the absorption of dietary calcium. We hypothesized that an HFD induces an increase in phosphorus absorption. The aim of this study was to evaluate the effects of differences in the quantity and quality of dietary fat on phosphorus metabolism over the short- and long-term. METHODS: Eighteen 8-wk-old Sprague-Dawley male rats were fed an isocaloric diet containing varied ratios of carbohydrates to fat energy and sources of fat (control diet, HFD, and high- saturated fat diet [HF-SFA]). At 3 d and 7 wk after the allocation and initiation of the test diets, feces and urine were collected and used for phosphorus and calcium measurement. RESULTS: The fecal phosphorous concentration (F-Pi) was lower in the HF-SFA group than in the other two groups; however, the urine phosphorus concentration (U-Pi) was significantly higher in the HF-SFA group than the other two groups when the rats were fed over the short- (P < 0.01) and long -term (P < 0.01 versus control, P < 0.05 versus HFD group). There were no significant differences in type-IIa sodium-phosphate cotransporter (NaPi-2 a) and type-IIc sodium-phosphate cotransporter (NaPi-2 c) mRNA expression, which are renal phosphate transport-related genes; however, the expression of type-IIb sodium-phosphate cotransporter (NaPi-2 b) and type-III sodium-phosphate cotransporter (Pit-1) mRNA in the duodenum was higher in the HFD and HF-SFA groups than in the control group (P < 0.05), although there were no significant differences in these in the jejunum. CONCLUSIONS: The present results indicated that an HFD, particularly HF-SFA, increases intestinal phosphate absorption compared with control.


Assuntos
Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/metabolismo , Fósforo/metabolismo , Animais , Cálcio/metabolismo , Duodeno/metabolismo , Fezes/química , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/metabolismo
5.
Med Sci Monit Basic Res ; 25: 187-198, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503241

RESUMO

BACKGROUND: This retrospective, historically controlled investigative study examined the benefit of a nutritional support pathway that included nutritional education before the start of conditioning and emphasized oral nutrition in response to nutrition-related adverse events in patients undergoing hematopoietic stem cell transplantation (HSCT). MATERIAL AND METHODS: Participants were patients undergoing allogeneic HSCT; 46 were in the control group (i.e., did not follow our nutritional pathway) and 36 were in the group that underwent nutritional intervention (enhanced nutrition group). We compared the following parameters between groups from the day before the start of conditioning to the day after completion of parenteral nutrition (PN): percent loss of body weight (%LBW), percent loss of skeletal muscle mass (%LSMM), and estimated basal energy expenditure (EBEE) sufficiency rate. The relationship between each parameter and %LBW was also examined. We also compared nutritional indices, gastrointestinal graft versus host disease (GvHD) grade, oral energy intake, and %LBW between groups. RESULTS: There was a relationship between %LBW, %LSMM, and EBEE sufficiency rate in both groups. Compared with the control group, the enhanced nutrition group had significantly improved energy intake amount, EBEE sufficiency rate, PN duration, and oral energy intake over time. The enhanced nutrition group also had increased oral energy intake, no difference in gastrointestinal GvHD grade, and improved %LBW compared with the control group. CONCLUSIONS: Use of our nutritional support pathway in patients undergoing HSCT may be beneficial for %LBW and gastrointestinal GvHD grade, enabling early enhanced nutritional intervention after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Apoio Nutricional/métodos , Redução de Peso/fisiologia , Adolescente , Adulto , Idoso , Peso Corporal/fisiologia , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral/métodos , Estudos Retrospectivos
6.
Med Sci Monit Basic Res ; 24: 31-39, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29398693

RESUMO

BACKGROUND The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. MATERIAL AND METHODS We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. RESULTS Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=-0.73, P=0.003; r=-0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). CONCLUSIONS Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Fenômenos Fisiológicos da Nutrição , Transplante de Células-Tronco de Sangue Periférico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/uso terapêutico , Ciclofosfamida/uso terapêutico , Ingestão de Energia , Etoposídeo/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos de Nitrosoureia/uso terapêutico , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
7.
Anal Bioanal Chem ; 408(22): 6063-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27039199

RESUMO

Cadmium is a highly toxic heavy metal for humans. In 2006, the Codex Alimentarius Commission set the international standard value of Cd contained in polished rice at 0.4 mg kg(-1), thus requiring the monitoring of Cd in food. We developed two types of Cd immunochromatographic kit by using anti-(Cd-EDTA) antibody. One is the quantitative Cd immunochromatographic device which can precisely measure Cd concentrations. The other is the Cd screening strip that enables visible evaluation of Cd exceeding 0.003 mg L(-1). Compared with conventional instrumental analysis methods, the immunoassay kits provide rapid, simple, and inexpensive on-site methods. For these kits, we also developed an efficient pretreatment method that can be easily administrated on-site. In this method, brown rice samples are coarsely crushed by a hand-held grinder then mixed with an enzyme solution, and Cd is extracted with HCl. The extracted solution is then purified by a newly developed Cd-selective ion exchange column. Cd concentrations measured by the quantitative Cd immunochromatographic devices correlated well with those obtained by ICP-OES (r (2) = 0.96). The Cd screening strips performed well in tests; pretreated purification solution which gave Cd concentrations exceeding 0.4 mg kg(-1) according to the Cd immunochromatographic devices gave corresponding results with the Cd screening strips with no false positives or false negatives. These results indicate that the two immunochromatographic kits are useful for on-site measurement of Cd concentrations and screening of Cd present in brown rice.


Assuntos
Anticorpos Imobilizados/química , Anticorpos Monoclonais/química , Cádmio/análise , Cromatografia de Afinidade/métodos , Oryza/química , Fitas Reagentes/análise , Cromatografia de Afinidade/instrumentação , Ácido Edético/química , Desenho de Equipamento , Coloide de Ouro/química , Humanos , Kit de Reagentes para Diagnóstico
8.
J Nutr Biochem ; 23(7): 785-90, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21889884

RESUMO

Cholesterol homeostasis is regulated by the liver X receptor (LXR) at the transcriptional level, but it remains unknown whether LXR can affect expression levels of intrahepatic lipolysis related gene. Recent evidence has demonstrated that fibroblast growth factor 21 (FGF21) regulates hepatic lipolysis and fatty acid utilization. In the present study, we examined the role of LXR in FGF21 gene expression associated with regulation of cross-talk signals between cholesterol and triglyceride metabolism in the liver. An in vivo cholesterol feeding test revealed that intake of excess cholesterol increased cholesterol catabolism related gene expression as well as fatty-acid biosynthesis related gene expression. Moreover, the accumulated cholesterol suppressed FGF21 and hormone-sensitive lipase (HSL) gene expression. After 15-day cholesterol feeding, hepatic triglyceride concentrations were negatively correlated with expression levels of the FGF21 and HSL genes in the liver. An LXR agonist (TO-901317) repressed the FGF21 gene expression in mouse primary hepatocytes and HepG2 cells. A promoter deletion study and electrophoretic mobility shift assay revealed that the human FGF21 promoter has at least one LXR response element located from -37 to -22 bp. In summary, LXR represses FGF21 gene expression at the transcription level and might suppress lipolysis and lipid utilization to protect the liver from excess accumulation of toxic cholesterol.


Assuntos
Colesterol na Dieta/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fatores de Crescimento de Fibroblastos/metabolismo , Receptores Nucleares Órfãos/metabolismo , Animais , Glicemia/análise , Fígado Gorduroso/induzido quimicamente , Fatores de Crescimento de Fibroblastos/genética , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Lipólise , Fígado/metabolismo , Receptores X do Fígado , Masculino , Camundongos , Regiões Promotoras Genéticas , Elementos de Resposta , Transdução de Sinais , Esterol Esterase/genética , Esterol Esterase/metabolismo , Triglicerídeos/sangue
9.
Biochim Biophys Acta ; 1791(1): 39-52, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18983939

RESUMO

Glycerol-3-phosphate acyltransferase 1 (GPAT1) is a rate limiting enzyme in de novo glycerophospholipid synthesis. The murine GPAT1 promoter sequence (the "classical" sequence) was reported previously. However, the organization of this DNA sequence does not fully match the mouse genome sequences on NCBI/GenBank. Here we have identified net cis-acting promoter sequences for the mouse GPAT1 gene: promoter 1a which includes part of the classical sequence and the downstream promoter 1b. Promoter 1a facilitates transcription of two alternative GPAT1 transcript variants, GPAT1-V1 and V2, while promoter 1b produces a third transcript variant, GPAT1-V3. Upstream stimulating factor-1 (USF-1) controlled both promoters whereas sterol regulatory element-binding protein-1 (SREBP-1) exclusively regulated promoter 1a activity in vitro. Feeding increased GPAT1-V1 and V2, but not V3 mRNA levels in mouse liver. The obese condition of db/db mice did not alter the hepatic expression levels of any of the three GPAT1 variants. Feeding enhanced hepatic mRNA levels, intranuclear protein levels and promoter 1a-binding levels of SREBP-1, but not of USF-1. Thus, promoter 1a was exclusively activated by routine feeding in vivo. Our results indicate differential roles of the two promoters in the regulation of hepatic GPAT1 gene expression in mice.


Assuntos
Glicerol-3-Fosfato O-Aciltransferase/genética , Regiões Promotoras Genéticas/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Regulação Enzimológica da Expressão Gênica , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Obesos , Interferência de RNA , Proteína de Ligação a Elemento Regulador de Esterol 1/fisiologia , Fatores Estimuladores Upstream/fisiologia
10.
Forum Nutr ; 60: 127-139, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17684409

RESUMO

BACKGROUND: Correcting postprandial hyperglycemia forms an important part of the prevention and management of type 2 diabetes. METHODS: A low-glycemic-index liquid formula designated as Inslow was prepared by replacing dextrin in the standard balanced formula (SBF) with 55.7% palatinose. Long-term administration of Inslow prevented fatty liver and improved insulin resistance in rats. Expressions of mRNA of factors involved in glucose and lipid metabolism were determined to clarify its mechanism. RESULTS: Analysis of mRNA expressions revealed that Inslow increased the expression of enzymes involved in Beta -oxidation and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in the liver, and increased PPAR-gamma, adiponectin and uncoupling protein 2 as well as decreased tumor necrosis factor alpha in adipose tissue in comparison with those of SBF. CONCLUSIONS: Inslow may induce improvement of insulin resistance by accelerated Beta-oxidation through increased expression of the hepatic PPAR-alpha gene and adipocyte PPAR-gamma gene. Therefore, Inslow is a functional food which prevents and treats type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Regulação da Expressão Gênica , Índice Glicêmico , PPAR alfa/genética , PPAR gama/genética , Animais , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Humanos , Estresse Oxidativo , Período Pós-Prandial
11.
J Nutr ; 137(8): 1908-15, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17634263

RESUMO

Excessive dietary intake of carbohydrates and fats has been linked to the development of obesity. However, the mechanism by which these dietary factors interact to bring about metabolic changes has not been elucidated. We examined the combined effects of different types of dietary carbohydrates and fats on the etiology of obesity and its complications in the Zucker fatty (fa/fa) rat, a model of obesity. Specifically, these rats were fed an isocaloric diet containing various combinations of carbohydrates [palatinose (P), an insulin-sparing sucrose analogue, and sucrose (S)] and fatty acids [oleic acid (O) and linoleic acid (L)]. After 8 wk, palatinose feeding (PO and PL) led to significant reductions in visceral fat mass, adipocyte cell size, hyperglycemia, and hyperlipidemia compared with sucrose feeding (SO and SL); pancreatic islet hypertrophy was also prevented by palatinose feeding. Linoleic-acid-fed rats (PL and SL) exhibited reduced insulin-immunoreactive staining of the pancreatic islets, enhanced macrophage infiltration in adipose tissue, and an elevated plasma tumor necrosis factor-alpha concentration when compared with oleic-acid-fed rats (PO and SO). Furthermore, sucrose and linoleic acid synergistically increased the expression of genes involved in hepatic gluconeogenesis and lipogenesis [sterol regulatory-element binding protein (SREBP)-1c and SREBP-2]. In conclusion, a diet containing palatinose and oleic acid may prevent diet-induced metabolic abnormalities. The combination of palatinose and oleic acid holds promise for a new approach to preventing and treating obesity and its complications.


Assuntos
Dieta , Glucose/metabolismo , Isomaltose/análogos & derivados , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Oleico/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Glicemia/efeitos dos fármacos , Peso Corporal , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Isomaltose/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pâncreas/efeitos dos fármacos , Ratos , Ratos Zucker , Triglicerídeos/sangue
12.
J Med Invest ; 52 Suppl: 295-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16366519

RESUMO

Oxidative stress has emerged as an important pathogenic factor in the development of long-term complications, such as hypertension, atherosclerosis, nephropathy, and cancer. Taking many antioxidants from natural food may be effective to prevent us from those diseases. We have attempted to evaluate the effect of improvement by dietary antioxidants on the endothelial dysfunction induced by hyperglycemia. Fluorescence indicators for reactive oxygen species and nitric oxide were employed to the evaluation. The combination of those fluorescence indicators could be powerful tool to evaluate the effect of anti-stress nutrients on both oxidative stress and endothelial dysfunction.


Assuntos
Antioxidantes/análise , Endotélio Vascular/efeitos dos fármacos , Glucose/farmacologia , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Aorta Torácica/citologia , Bovinos , Técnicas de Cultura de Células , Células Cultivadas , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Corantes Fluorescentes , Hiperglicemia/metabolismo , Microscopia Confocal , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
13.
Kidney Int ; 68(3): 1137-47, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16105044

RESUMO

BACKGROUND: Parathyroid hormone (PTH) rapidly down-regulates type IIa sodium-dependent phosphate transporter (NaPi-IIa) via an endocytic pathway. Since the relationship between PTH signaling and NaPi-IIa endocytosis has not been explored, we investigated the role of membrane microdomains in this process. METHODS: We examined the submembrane localization of NaPi-IIa in opossum kidney (OK-N2) cells that stably expressed human NaPi-IIa, and searched for a PTH-induced specific phosphorylating substrate on their membrane microdomains by immunoblotting with specific antibody against phospho substrates of protein kinases. RESULTS: We found that NaPi-IIa was primarily localized in low-density membrane (LDM) domains of the plasma membrane; PTH reduced the levels of immunoreactive NaPi-IIa in these domains. Furthermore, PTH activated both protein kinase A (PKA) and protein kinase Calpha (PKCa) and increased the phosphorylation of 250 kD and 80 kD substrates; this latter substrate was identified as ezrin, which a member of the ezrin-radixin-moesin (ERM) protein family. In response to PTH, ezrin was phosphorylated by both PKA and PKC. Dominant negative ezrin blocked the reduction in NaPi-IIa expression in the LDM domains that was induced by PTH. CONCLUSION: These data suggest that NaPi-IIa and PTH-induced phosphorylated proteins that include ezrin are compartmentalized in LDM microdomains. This compartmentalization may play an important role in the down-regulation of NaPi-IIa via endocytosis.


Assuntos
Compartimento Celular/fisiologia , Endocitose/fisiologia , Rim/citologia , Hormônio Paratireóideo/farmacologia , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Clorpromazina/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ciclodextrinas/farmacologia , Citocalasina D/farmacologia , Proteínas do Citoesqueleto , Antagonistas de Dopamina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Nocodazol/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Gambás , Fosfatos/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Proteína Quinase C-alfa/metabolismo , Estrutura Terciária de Proteína , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/química , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética
14.
J Cell Mol Med ; 8(2): 191-200, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15256067

RESUMO

Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by Pi, parathyroid hormone and by 1,25-dihydroxyvitamin D. Recent studies of inherited and acquired hypophosphatemia [X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and tumor-induced rickets/osteomalacia (TIO)], which exhibit similar biochemical and clinical features, have led to the identification of novel genes, PHEX and FGF23, that play a role in the regulation of Pi homeostasis. The PHEX gene, which is mutated in XLH, encodes an endopeptidase, predominantly expressed in bone and teeth, but not in kidney. FGF-23 may be a substrate of this endopeptidase and may therefore accumulate in patients with XLH. In the case of ADHR mutations in the furin cleavage site, which prevent the processing of FGF-23 into fragments, lead to the accumulation of a "stable" circulating form of the peptide which also inhibits renal Pi reabsorption. In the case of TIO, ectopic overproduction of FGF-23 overwhelms its processing and degradation by PHEX, leading to the accumulation of FGF-23 in the circulation and inhibition of renal Pi reabsorption. Mice homozygous for severely hypomorphic alleles of the Klotho gene exhibit a syndrome resembling human aging, including atherosclerosis, osteoporosis, emphysema, and infertility. The KLOTHO locus is associated with human survival, defined as postnatal life expectancy, and longevity, defined as life expectancy after 75. In considering the relationship of klotho expression to the dietary Pi level, the klotho protein seemed to be negatively controlled by dietary Pi.


Assuntos
Dieta , Homeostase , Fosfatos/metabolismo , Fosfatos/farmacologia , Animais , Fator de Crescimento de Fibroblastos 23 , Homeostase/efeitos dos fármacos , Humanos , Hipofosfatemia Familiar/metabolismo , Osteomalacia/metabolismo , Fosfatos/administração & dosagem
15.
J Am Coll Cardiol ; 42(8): 1389-94, 2003 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-14563580

RESUMO

OBJECTIVES: We examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment-elevated acute myocardial infarction (AMl). BACKGROUND: Activated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro. METHODS: After successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10). RESULTS: Adverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group). CONCLUSIONS: Administration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients.


Assuntos
Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteína C/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Anal Sci ; 19(7): 1061-4, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12880093

RESUMO

Cadmium ranging from 1 - 8 ng could be coprecipitated quantitatively with lanthanum phosphate at pH 5 - 6 from up to 200 mL of river water samples spiked with 5 microg of indium as an internal standard. Cadmium and indium coprecipitated were measured by using electrothermal atomic absorption spectrometry. The cadmium content in the original sample solution could be determined by internal standardization with indium. Since complete collection of the precipitate and strict adjustment of the volume of the final solution after coprecipitation are not required in this method, the precipitate could be collected by using decantation and centrifugation, and then dissolved with 1 mL of about 2.4 mol L(-1) nitric acid. The proposed method is simple and rapid, and enrichment close to 200-times can be attained; the detection limit (3sigma, n = 6) was 0.63 ng L(-1) in 200 mL of the sample solution.


Assuntos
Cádmio/análise , Água Doce/química , Fosfatos/química , Espectrofotometria Atômica/métodos , Poluição Química da Água/análise , Cádmio/química , Precipitação Química , Japão
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