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[Purpose] The effect of heel lift insertion on gait in patients who have undergone total hip arthroplasty (THA) with patient-perceived leg length difference is seldom referenced in the literature. We used an AB design to investigate the alterations of gait function before and after inserting a heel lift on the non-operative side. [Participant and Methods] The participant had a patient-perceived leg length difference after THA and presented with gait disturbance. The survey phase was 10 days (phase A: normal physiotherapy for five days, and phase B: normal physiotherapy and heel lift insertion for another five days) from the 17th day following THA. The ambulatory task was conducted at a self-determined, comfortable pace and objectively assessed using an inertial sensor. [Results] The insertion of a heel lift partially improved the gait symmetry and the ratio of lumbar acceleration in three directions; it also corrected the patient-perceived leg length difference. [Conclusion] An investigation was carried out to examine the impact of a heel lift on gait in a single case of THA with patient-reported leg length difference. The application of a heel lift may enhance the relationship between the patient-perceived leg length difference, gait symmetry, and the ratio of lumbar acceleration in three dimensions.
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BACKGROUND: High peritoneal transport is associated with high mortality and technical failure in peritoneal dialysis (PD). Baseline peritoneal solute transport rate (PSTR) as measured by the peritoneal equilibration test (PET) within 6 months after PD initiation varies between patients. Sodium is reported to be stored in the skin or muscle of dialysis patients. This study investigated whether excessive salt intake in uremic mice caused peritoneal alterations without exposure to PD fluid. METHODS: Sham-operated (Sham) and subtotal nephrectomized (Nx) mice were randomly given tap water or 1% sodium chloride (NaCl)-containing water for 8 weeks. PET was then performed to evaluate peritoneal function. Human mesothelial cell line Met-5A was used for in vitro studies. RESULTS: We observed higher PSTR in Nx mice with 1% NaCl-containing drinking water (Nx + salt) compared with those with tap water (Nx + water), along with enhanced angiogenesis and inflammation in the peritoneum. Blockade of interleukin (IL)-6 signaling rescued peritoneal transport function in Nx + salt mice. In cultured Met-5A, additional NaCl in the medium upregulated IL-6 as well as vascular endothelial growth factor-A, associated with increased expression and nuclear translocation of tonicity-responsive enhancer binding protein (TonEBP). Knockdown of TonEBP lowered the induction caused by high tonicity. Peritoneal TonEBP expression was higher in Nx + salt mice, while removal of high-salt diet lowered TonEBP level and improved peritoneal transport function. CONCLUSIONS: Excessive dietary salt intake caused peritoneal membrane functional and structural changes under uremic status. TonEBP regulated hypertonicity-related inflammatory changes and might play a crucial role in high baseline peritoneal transport.
Assuntos
Aromatizantes/toxicidade , Inflamação/patologia , Rim/patologia , Fatores de Transcrição NFATC/metabolismo , Peritonite/patologia , Cloreto de Sódio na Dieta/toxicidade , Uremia/patologia , Animais , Soluções para Diálise/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/cirurgia , Masculino , Camundongos , Fatores de Transcrição NFATC/genética , Nefrectomia , Diálise Peritoneal , Peritonite/induzido quimicamente , Peritonite/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima , Uremia/induzido quimicamente , Uremia/metabolismoRESUMO
BACKGROUND: Ultrafiltration failure associated with peritoneal membrane dysfunction is one of the main complications for patients on long-term peritoneal dialysis (PD). The dialysate-to-plasma concentration ratio (D/P) of creatinine is widely used to assess peritoneal membrane function. However, other small-sized solutes have not been studied in detail as potential indicators of peritoneal permeability. METHODS: We studied the D/Ps of small, middle-sized and large molecules in peritoneal equilibration tests in 50 PD patients. We applied metabolomic analysis of comprehensive small molecular metabolites using capillary electrophoresis time-of-flight mass spectrometry. RESULTS: D/Ps of middle-sized and large molecules correlated positively with D/P creatinine. Most D/Ps of small molecules correlated positively with D/P creatinine. Among 38 small molecules contained in the dialysate, urea, citrulline and choline showed significantly lower ability to permeate than creatinine. In the relationship between D/Ps of creatinine and small molecules, regression coefficients of three molecules were less than 0.3, representing no correlation to D/P creatinine. Five molecules showed negative regression coefficients. Among these molecules, hippurate and 3-indoxyl sulfate showed relatively high teinpro binding rates, which may affect permeability. Serum concentrations of two molecules were higher in the Low Kt/V group, mainly due to high protein binding rates. CONCLUSIONS: D/Ps of some molecules did not correlate with D/P creatinine. Factors other than molecular weight, such as charge and protein binding rate, are involved in peritoneal transport rates. Metabolomic analysis appears useful to analyze small molecular uremic toxins, which could accumulate in PD patients, and the status of peritoneal membrane transport for each molecule.
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Diálise Peritoneal , Peritônio/metabolismo , Idoso , Biomarcadores/sangue , Creatinina/análise , Creatinina/sangue , Soluções para Diálise , Eletroforese Capilar , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Peso Molecular , Permeabilidade , Ligação Proteica , UltrafiltraçãoRESUMO
Little is known about the role of the central melanocortin system in the control of fuel metabolism in peripheral tissues. Skeletal muscle AMP-activated protein kinase (AMPK) is activated by leptin and serves as a master regulator of fatty acid beta-oxidation. To elucidate an unidentified role of the central melanocortin system in muscle AMPK regulation, we treated conscious, unrestrained mice intracerebroventricularly with the melanocortin agonist MT-II or the antagonist SHU9119. MT-II augmented phosphorylation of AMPK and its target acetyl-CoA carboxylase (ACC) independent of caloric intake. Conversely, AMPK/ACC phosphorylation by leptin was abrogated by the coadministration of SHU9119 or in KKA(y) mice, which centrally express endogenous melanocortin antagonist. Importantly, high-fat-diet-induced attenuation of AMPK/ACC phosphorylation in leptin-overexpressing transgenic mice was not reversed by central leptin but was markedly restored by MT-II. Our data provide evidence for the critical role of the central melanocortin system in the leptin-skeletal muscle AMPK axis and highlight the system as a therapeutic target in leptin resistance.
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Melanocortinas/metabolismo , Músculo Esquelético/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais/fisiologia , Quinases Proteína-Quinases Ativadas por AMP , Análise de Variância , Animais , Western Blotting , Gorduras na Dieta , Leptina/metabolismo , Melanocortinas/agonistas , Melanocortinas/antagonistas & inibidores , Hormônios Estimuladores de Melanócitos/farmacologia , Metalotioneína/farmacologia , Camundongos , Fosforilação/efeitos dos fármacosRESUMO
AIM: Severe post-partum hemorrhage during cesarean section due to placenta previa is still one of the leading causes of maternal mortality. The aim of this study was to evaluate the efficiency of intrauterine tamponade with a Sengstaken-Blakemore tube (SB-tube) for the treatment of severe post-partum hemorrhage in cases of placenta previa. MATERIAL AND METHODS: Data were collected from our departmental clinical records on all patients who underwent caesarian section due to placenta previa between 2007 and 2009. RESULTS: During the period analyzed, 37 patients underwent caesarian section due to placenta previa/low-lying placenta. Four (11%) underwent hysterectomy due to placenta accreta and 33 (89%) were treated conservatively. Of the 33 patients with conserved uterus, 10 (28%) patients required a SB-tube during the cesarean section because of continuous post-partum hemorrhage despite appropriate medical treatment. The median bleeding during the operation was 2030±860mL in the patients who used SB-tube. None of them presented severe complications related to these procedures or required any further invasive surgery. CONCLUSION: Intrauterine balloon-tamponade could successfully control severe hemorrhage from a lower uterine segment of a patient with placenta previa. This technique is simple to use, scarcely invasive, and available at a low cost to all maternity wards, and should be considered as one of the first management options to reduce the risk of undesirable hysterectomy.
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Cesárea/efeitos adversos , Placenta Prévia/cirurgia , Hemorragia Pós-Parto/terapia , Tamponamento com Balão Uterino/métodos , Hemorragia Uterina/terapia , Adulto , Feminino , Humanos , Hemorragia Pós-Parto/etiologia , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia Uterina/etiologiaRESUMO
Macrophage infiltration in obese adipose tissue provokes local inflammation and insulin resistance. Evidence has accumulated that activation of 11beta-HSD1 in adipocytes is critically involved in dysfunction of adipose tissue. However, the potential role of 11beta-HSD1 in macrophages still remains unclear. We here demonstrate that a murine macrophage cell line, J774.1 cells expressed 11beta-HSD1 mRNA and reductase activity, both of which were augmented by lipopolysaccharide (LPS)-induced cell activation. Three kinds of pharmacological inhibition of 11beta-HSD1 in LPS-treated macrophages significantly suppressed the expression and secretion of interleukin 1beta, tumor necrosis factor alpha or monocyte chemoattractant protein 1, thereby highlighting a novel role of 11beta-HSD1 in pro-inflammatory properties of activated macrophages.
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11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Macrófagos/enzimologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Adipócitos/fisiologia , Animais , Sequência de Bases , Linhagem Celular , Primers do DNA/genética , Dexametasona/farmacologia , Inflamação/patologia , Inflamação/fisiopatologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Obesidade/patologia , Obesidade/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The metamorphosis of anuran amphibians is induced by thyroid hormone (TH). To study the molecular mechanisms underlying tail regression during metamorphosis, we established a cell line, XL-B4, from a Xenopus laevis tadpole tail at a premetamorphic stage. The cells expressed myoblast markers and differentiated into myotubes in differentiation medium. XL-B4 cells expressing fluorescent proteins were transplanted into tadpole tails. At 5 days post-transplantation, fluorescence was observed in myotube-like structures, indicating that the myoblastic cells could contribute to skeletal muscle. Exposure of XL-B4 cells to the TH triiodothyronine (T3) for several days significantly induced apoptotic cell death. We then examined an early response of expression of genes involved in apoptosis or myogenesis to T3. Treatment of the cells with T3 increased transcription of genes for matrix metalloproteinase-9 (MMP-9) and thyroid hormone receptor beta. Interestingly, the T3-treatment also increased myoD transcripts, but decreased the amounts of myogenin mRNA and myosin heavy chain. Importantly, we also observed upregulation of myoD expression and downregulation of myogenin expression in tails, but not in hind limbs, when tadpoles at a premetamorphic stage were treated with T3 for 1 day. These results indicated that T3 could not only induce apoptosis, but also attenuate myogenesis in tadpole tails during metamorphosis.
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Apoptose , Diferenciação Celular , Mioblastos/fisiologia , Tri-Iodotironina/fisiologia , Animais , Linhagem Celular , Feminino , Expressão Gênica , Masculino , Miogenina/genética , Miogenina/metabolismo , Cauda , Xenopus laevisRESUMO
BACKGROUND: The adipose tissue renin-angiotensin system (RAS) has been implicated in the pathophysiology of obesity and dysfunction of adipose tissue. However, neither regulation of angiotensinogen (AGT) expression in adipose tissue nor secretion of adipose tissue-derived AGT has been fully elucidated in humans. METHODS: Human subcutaneous abdominal adipose tissue (SAT) biopsies were performed for 46 subjects with a wide range of body mass index (BMI). Considering the mRNA level of AGT and indices of body fat mass, the amount of adipose tissue-derived AGT secretion (A-AGT-S) was estimated. Using a mouse model of obesity and weight reduction, plasma AGT levels were measured with a newly developed enzyme-linked immunosorbent assay (ELISA), and the contribution of A-AGT-S to plasma AGT levels was assessed. RESULTS: A-AGT-S was substantially increased in obese humans and the value was correlated with the plasma AGT level in mice. A-AGT-S and plasma AGT were higher in obese mice, whereas lower in mice with weight reduction. However, the AGT mRNA levels in the liver, kidney, and aorta were not altered in the mouse models. In both humans and mice, the AGT mRNA levels in mature adipocytes (MAs) were comparable to those in stromal-vascular cells. Coulter Multisizer analyses revealed that AGT mRNA levels in the MAs were inversely correlated with the average size of mature adipocytes. CONCLUSIONS: This study demonstrates that adipose tissue-derived AGT is substantially augmented in obese humans, which may contribute considerably to elevated levels of circulating AGT. Adipose tissue-specific regulation of AGT provides a novel insight into the clinical implications of adipose tissue RAS in human obesity.
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Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Angiotensinogênio/metabolismo , Estado Nutricional , Obesidade/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Adulto , Angiotensinogênio/sangue , Angiotensinogênio/genética , Animais , Aorta/metabolismo , Crescimento Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Humanos , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologia , RNA Mensageiro/metabolismo , Renina/genética , Renina/metabolismoRESUMO
OBJECTIVE: Dysregulation of tissue-specific intracellular glucocorticoid reactivation is implicated in obesity and related metabolic diseases in humans. The ratio of end products of glucocorticoid metabolism in fresh urine sample, tetrahydrocortisol (THF) + allo-tetrahydrocortisol (allo-THF) vs. tetrahydrocortisone (THE), i.e., the urinary ratio is regarded as an index of the systemic balance underlying intracellular glucocorticoid metabolism, where the enzymes, 11ß-hydroxysteroid dehydrogenase type 1 and type 2 as well as 5α- and 5ß-reductase are involved in a tissue-specific manner. METHODS: To explore the clinical implications of the urinary ratio in obesity and related metabolic diseases, the urinary ratio was determined by gas chromatography and mass spectrometry. RESULTS: The urinary ratio was shown to be constant and reproducible in the same individuals. The ratio was found to inversely correlate with BMI (P < 0.01), waist circumference (P < 0.01), and liver transaminase (P < 0.05) in a large cohort of â¼200 Japanese subjects. This finding suggests that the systemic balance underlying intracellular glucocorticoid reactivation was suppressed in obesity and liver dysfunction. Consistent with this notion, the ratio was decreased in patients with non-alcoholic steatohepatitis (P < 0.01). The urinary ratio was not altered in patients with type 2 diabetes on a 2-month mild calorie restriction. In contrast, the ratio was significantly reduced in patients who responded to the anti-diabetic pioglitazone (P < 0.01). CONCLUSION: The present study provides novel evidence that the urinary ratio reflects the facet of adipose tissue and liver function in humans, thereby offering a unique opportunity to evaluate obesity-related diseases.
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A clinically employed antihyperlipidemic drug, bezafibrate, has been characterized as a PPAR(alpha, -gamma, and -delta) pan-agonist in vitro. Recent extended trials have highlighted its antidiabetic properties in humans. However, the underlying molecular mechanism is not fully elucidated. The present study was designed to explore potential regulatory mechanisms of intracellular glucocorticoid reactivating enzyme, 11beta-HSD1 and anti-diabetic hormone, adiponectin by bezafibrate in murine adipose tissue, and cultured adipocytes. Treatment of db/db mice with bezafibrate significantly ameliorated hyperglycemia and insulin resistance, accompanied by a marked reduction of triglyceride and nonesterified fatty acids. Despite equipotent in lipid-lowering effects, another fibrate, fenofibrate, did not show such beneficial effects on glycemic control. Treatment of bezafibrate caused a marked decrease in the mRNA level of 11beta-HSD1 preferentially in adipose tissue of db/db mice (-47%, P<0.05), concomitant with a significant increase in plasma adiponectin level (+37%, P<0.01). Notably, treatment of bezafibrate caused a marked decrease in the mRNA level (-34%, P<0.01) and enzyme activity (-32%, P<0.01) of 11beta-HSD1, whereas the treatment substantially augmented the expression (+71%, P<0.01) and secretion (+27%, P<0.01) of adiponectin in 3T3-L1 adipocytes. Knockdown of 11beta-HSD1 by siRNA confirmed that 11beta-HSD1 acts as a distinct oxoreductase in adipocytes and validated the enzyme activity assays in the present study. Effects of bezafibrate on regulation of 11beta-HSD1 and adiponectin in murine adipocytes were comparable with those in thiazolidinediones. This is the first demonstration that bezafibrate directly regulates 11beta-HSD1 and adiponectin in murine adipocytes, both of which may contribute to metabolically-beneficial effects by bezafibrate.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Adipócitos/metabolismo , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Bezafibrato/farmacologia , Diabetes Mellitus/metabolismo , Hipolipemiantes/farmacologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/enzimologia , Adiponectina/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/enzimologia , Animais , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Diabetes Mellitus/fisiopatologia , Ácidos Graxos não Esterificados/sangue , Hiperglicemia/etiologia , Hiperglicemia/fisiopatologia , Resistência à Insulina , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Tamanho do Órgão/efeitos dos fármacos , Oxirredutases/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , RNA Mensageiro/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Triglicerídeos/sangueRESUMO
Rho-associated kinase (ROCK) regulates reorganization of actin cytoskeleton. During adipogenesis, the structure of filamentous actin is converted from long stress fibers to cortical actin, suggesting that the ROCK is involved in adipogenesis. Two ROCK isoforms have been identified: ROCK-I and ROCK-II. However, pharmacological inhibitors of ROCK cannot distinguish two ROCK isoforms. In the present study, we examined the role of ROCK in adipogenesis and actin cytoskeleton using genetic and pharmacological approaches. Y-27632, which inhibits the activity of both ROCK isoforms, enhanced adipogenesis through the up-regulation of adipogenic transcription factors in 3T3-L1 cells. Furthermore, Y-27632 restored inhibition of adipogenesis by lysophosphatidic acid, which activates Rho. Regarding actin cytoskeleton, Y-27632 disrupted stress fibers in 3T3-L1 preadipocytes. Next, we analyzed adipogenesis of mouse embryonic fibroblasts (MEFs) derived from ROCK-I and ROCK-II knock-out mice, respectively. Adipogenesis of ROCK-II (-/-) MEFs was markedly enhanced compared with wild-type MEFs while that of ROCK-I (-/-) MEFs was not. In contrast to pharmacological approaches, no obvious alteration was found in actin cytoskeleton of ROCK-II (-/-) MEFs compared with wild-type MEFs. In 3T3-L1 cells, knockdown of ROCK-II by RNA interference enhanced the expression of adipogenic transcription factors while that of ROCK-I did not. Moreover, Y-27632 inhibited IRS-1 serine phosphorylation and enhanced Akt phosphorylation in 3T3-L1 preadipocytes. Similarly, Akt phosphorylation in ROCK-II (-/-) MEFs was augmented compared with wild-type MEFs. In conclusion, inhibition of ROCK-II, not ROCK-I, enhances adipogenesis accompanied by the up-regulation of adipogenic transcription factors. Augmentation of insulin signaling may contribute to the enhancement of adipogenesis.
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Adipócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Células 3T3-L1 , Actinas/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Citoesqueleto/metabolismo , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Insulina/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos , Modelos Genéticos , Transdução de Sinais , Quinases Associadas a rhoRESUMO
In male rats challenged with the environmental estrogen bisphenol A, the compound is highly glucuronidated in the liver and is excreted largely into the bile. Given that in pregnancy the microsomal glucuronidation toward bisphenol A is attenuated, we hypothesized that elimination of bisphenol A from the liver may be reduced in pregnancy. This study was conducted to trace the elimination of bisphenol A in female rats, especially in pregnancy. In Sprague-Dawley rats, 1.5 mumol of bisphenol A was perfused into the liver via the portal vein. In both the male and the nonpregnant female, the infused bisphenol A was glucuronidated, then the resultant glucuronide was excreted mainly into the bile. In pregnant rats, however, bilious excretion of bisphenol A glucuronide was 60% of that observed in nonpregnant rats, and venous excretion increased reciprocally. During 1-h perfusion, total excretion of the glucuronide from the liver of male, nonpregnant female, and pregnant rats was 889.5 +/- 69.6, 1256.7 +/- 54.8, and 1038.8 +/- 33.3 nmoles, respectively. In Eisai hyperbilirubinemic rats (EHBR), perfusion of the liver with bisphenol A enabled us to determine that multidrug resistance-associated protein (MRP)2-mediating transport is the mechanism behind excretion of the glucuronide into the bile. The expression of MRP2 has been reported to be noticeably reduced in pregnancy. These results suggest that bisphenol A elimination by hepatic glucuronidation is slightly less in pregnancy than in non-pregnancy and that in pregnancy, more bisphenol A glucuronide is eliminated to the vein because of reduced MRP2 expression.