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1.
Genes Cells ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39394696

RESUMO

The mammalian p57 protein is a member of the CIP/KIP family of cyclin-dependent kinase inhibitors and plays an essential role in the development of multiple tissues during embryogenesis as well as in the maintenance of tissue stem cells in adults. Although several transcription factors have been implicated in regulating the p57 gene, cis-elements such as enhancers that regulate its expression have remained ill-defined. Here we identify a candidate enhancer for the mouse p57 gene (Cdkn1c) within an intron of the Kcnq1 locus by 4C-seq analysis in mouse embryonic stem cells (mESCs). Deletion of this putative enhancer region with the CRISPR-Cas9 system or its suppression by CRISPR interference resulted in a marked attenuation of Cdkn1c expression in differentiating mESCs. Our results thus suggest that this region may serve as an enhancer for the p57 gene during early mouse embryogenesis.

2.
Acta Neuropathol ; 145(5): 637-650, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36879070

RESUMO

A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. The M232R substitution did not alter the attachment of GPI nor GPI-attachment site. Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease.


Assuntos
Síndrome de Creutzfeldt-Jakob , Doenças Priônicas , Príons , Animais , Camundongos , Humanos , Proteínas Priônicas/genética , Mutação Puntual , Glicosilfosfatidilinositóis/genética , Glicosilfosfatidilinositóis/metabolismo , Sinais Direcionadores de Proteínas/genética , Doenças Priônicas/genética , Doenças Priônicas/patologia , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Príons/genética , Príons/metabolismo , Mutação/genética
3.
J Cell Sci ; 132(3)2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30659120

RESUMO

Endocytic trafficking is regulated by ubiquitylation (also known as ubiquitination) of cargoes and endocytic machineries. The role of ubiquitylation in lysosomal delivery has been well documented, but its role in the recycling pathway is largely unknown. Here, we report that the ubiquitin (Ub) ligase RFFL regulates ubiquitylation of endocytic recycling regulators. An RFFL dominant-negative (DN) mutant induced clustering of endocytic recycling compartments (ERCs) and delayed endocytic cargo recycling without affecting lysosomal traffic. A BioID RFFL interactome analysis revealed that RFFL interacts with the Rab11 effectors EHD1, MICALL1 and class I Rab11-FIPs. The RFFL DN mutant strongly captured these Rab11 effectors and inhibited their ubiquitylation. The prolonged interaction of RFFL with Rab11 effectors was sufficient to induce the clustered ERC phenotype and to delay cargo recycling. RFFL directly ubiquitylates these Rab11 effectors in vitro, but RFFL knockout (KO) only reduced the ubiquitylation of Rab11-FIP1. RFFL KO had a minimal effect on the ubiquitylation of EHD1, MICALL1, and Rab11-FIP2, and failed to delay transferrin recycling. These results suggest that multiple Ub ligases including RFFL regulate the ubiquitylation of Rab11 effectors, determining the integral function of the ERC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Endossomos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Transporte Vesicular/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Transporte Biológico , Linhagem Celular , Endocitose/genética , Células HEK293 , Células HeLa , Humanos , Lisossomos/metabolismo , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Ligação Proteica , Mapeamento de Interação de Proteínas , Transferrina/genética , Transferrina/metabolismo , Ubiquitinação , Proteínas de Transporte Vesicular/genética , Proteínas rab de Ligação ao GTP/genética
4.
Eur J Orthop Surg Traumatol ; 31(4): 743-753, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33169175

RESUMO

PURPOSE: Short stems have recently become popular in total hip arthroplasty. Previous studies aimed at elucidating the efficacy of short stems did not eliminate the influence of other factors aside from stem length. This study aimed to evaluate the usefulness of short stems compared with that of standard-length stems that have the same proximal morphology, surface coating, and material. METHODS: This was a prospective randomized study comparing 5-year midterm outcomes in 29 patients who underwent one-stage bilateral total hip arthroplasty with short and standard-length stems inserted in each of the two femurs. Clinical, radiographical, and dual-energy X-ray absorptiometry outcomes were compared. RESULTS: No significant differences were found in perioperative and radiographic characteristics (femoral neck anteversion, flare index, operation sequence, operation side, operation time, stem anteversion, and stem alignment). The number of joints with complications, appearance of radiopaque lines around the stems, or bone mineral density changed in stem regions 5 years postoperatively. However, greater micromotion of the stem was seen on the side of the short stem. Satisfactory improvement in hip function was seen on both sides. CONCLUSION: Based on the 5-year midterm outcomes, both stems obtained satisfactory clinical outcomes despite the greater micromotion with short stems. Both stems attained bone ingrowth fixation. Moreover, the stems were not significantly different in terms of stress shielding; however, further long-term studies (> 5 years) are required to validate our findings related to stress shielding.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Artroplastia de Quadril/efeitos adversos , Densidade Óssea , Fêmur/cirurgia , Humanos , Estudos Prospectivos , Desenho de Prótese
5.
Am J Physiol Heart Circ Physiol ; 318(2): H283-H294, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834837

RESUMO

The ß3-adrenergic receptor (ß3AR) is related to myocardial fatty acid metabolism and its expression has been implicated in heart failure. In this study, we investigated the role of ß3AR in sepsis-related myocardial dysfunction using lipopolysaccharide (LPS)-induced endotoxemia as a model of cardiac dysfunction. We placed mice into three treatment groups and treated each with intraperitoneal injections of the ß3AR agonist CL316243 (CL group), the ß3AR antagonist SR59230A (SR group), or normal saline (NS group). Survival rates were significantly improved in the SR group compared with the other treatment groups. Echocardiography analyses revealed cardiac dysfunction within 6-12 h of LPS injections, but the outcome was significantly better for the SR group. Myocardial ATP was preserved in the SR group but was decreased in the CL-treated mice. Additionally, quantitative PCR analysis revealed that expression levels of genes associated with fatty acid oxidation and glucose metabolism were significantly higher in the SR group. Furthermore, the expression levels of mitochondrial membrane protein complexes were preserved in the SR group. Electron microscope studies showed significant accumulation of lipid droplets in the CL group. Moreover, inducible nitric oxide synthase (iNOS) protein expression and nitric oxide were significantly reduced in the SR group. The in vitro study demonstrated that ß3AR has an independent iNOS pathway that does not go through the nuclear factor-κB pathway. These results suggest that blockading ß3AR improves impaired energy metabolism in myocardial tissues by suppressing iNOS expression and recovers cardiac function in animals with endotoxin-induced heart failure.NEW & NOTEWORTHY Nitric oxide production through stimulation of ß3-adrenergic receptor (ß3AR) may improve cardiac function in cases of chronic heart failure. We demonstrated that the blockade of ß3AR improved mortality and cardiac function in endotoxin-induced heart failure. We also determined that LPS-induced inducible nitric oxide synthase has a pathway that is independent of nuclear factor-κB, which worsened cardiac metabolism and mortality in the acute phase of sepsis. Treatment with the ß3AR antagonist had a favorable effect. Thus, the blockade of ß3AR could offer a novel treatment for sepsis-related heart failure.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Propanolaminas/uso terapêutico , Trifosfato de Adenosina/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Animais , Ácidos Graxos/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética
6.
J Anat ; 237(3): 427-438, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32786168

RESUMO

Trunk muscles in vertebrates are classified as either dorsal epaxial or ventral hypaxial muscles. Epaxial and hypaxial muscles are defined as muscles innervated by the dorsal and ventral rami of spinal nerves, respectively. Each cluster of spinal motor neurons passing through dorsal rami innervates epaxial muscles, whereas clusters traveling on the ventral rami innervate hypaxial muscles. Herein, we show that some motor neurons exhibiting molecular profiles for epaxial muscles follow a path in the ventral rami. Dorsal deep-shoulder muscles and some body wall muscles are defined as hypaxial due to innervation via the ventral rami, but a part of these ventral rami has the molecular profile of motor neurons that innervate epaxial muscles. Thus, the epaxial and hypaxial boundary cannot be determined simply by the ramification pattern of spinal nerves. We propose that, although muscle innervation occurs via the ventral rami, dorsal deep-shoulder muscles and some body wall muscles represent an intermediate group that lies between epaxial and hypaxial muscles.


Assuntos
Neurônios Motores/citologia , Músculo Esquelético/inervação , Somitos/inervação , Nervos Espinhais/embriologia , Animais , Padronização Corporal , Embrião de Galinha , Coturnix , Músculo Esquelético/embriologia , Tubo Neural , Somitos/embriologia , Tronco/embriologia , Tronco/inervação
7.
Biochem J ; 476(5): 827-842, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30787050

RESUMO

To closely mimic physiological conditions, low oxygen cultures have been employed in stem cell and cancer research. Although in vivo oxygen concentrations in tissues are often much lower than ambient 21% O2 (ranging from 3.6 to 12.8% O2), most cell cultures are maintained at 21% O2 To clarify the effects of the O2 culture concentration on the regulated secretion of peptide hormones in neuro-endocrine cells, we examined the changes in the storage and release of peptide hormones in neuro-endocrine cell lines and endocrine tissues cultured in a relatively lower O2 concentration. In both AtT-20 cells derived from the mouse anterior pituitary and freshly prepared mouse pituitaries cultured in 10% O2 for 24 h, the storage and regulated secretion of the mature peptide hormone adrenocorticotropic hormone were significantly increased compared with those in cells and pituitaries cultured in ambient 21% O2, whereas its precursor proopiomelanocortin was not increased in the cells and tissues after being cultured in 10% O2 Simultaneously, the prohormone-processing enzymes PC1/3 and carboxypeptidase E were up-regulated in cells cultured in 10% O2, thus facilitating the conversion of prohormones to their active form. Similarly, culturing the mouse ß-cell line MIN6 and islet tissue in 10% O2 also significantly increased the conversion of proinsulin into mature insulin, which was secreted in a regulated manner. These results suggest that culture under 10% O2 is more optimal for endocrine tissues/cells to efficiently generate and secrete active peptide hormones than ambient 21% O2.


Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Neuroendócrinas/metabolismo , Oxigênio/farmacologia , Adeno-Hipófise/metabolismo , Pró-Opiomelanocortina/biossíntese , Regulação para Cima/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Linhagem Celular , Camundongos
8.
Anal Chem ; 90(8): 5329-5334, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29595058

RESUMO

We report on the development of a novel and flexible online digital polymerase chain reaction (dPCR) system. The system was composed of three parts: an inkjet for generating the droplets, a coiled fused-silica capillary for thermal cycling, and a laser-induced fluorescence detector (LIFD) for positive droplet counting. Upon inkjet printing, monodisperse droplets were continuously generated in the oil phase and then introduced into the capillary in the form of a stable dispersion. The droplets containing one or zero molecules of target DNA passed through the helical capillary that was attached to a cylindrical thermal cycler for PCR amplification, resulting in the generation of fluorescence for the DNA-positive droplet. After 36 PCR cycles, the fluorescence signal intensity was detected by laser-induced fluorescence located at the downstream of the capillary, followed by a positive/negative counting. The present system was successfully applied to the absolute quantification of the HPV sequence in Caski cells with dynamic ranges spanning 4 orders of magnitude.


Assuntos
DNA/genética , Tinta , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Impressão , Linhagem Celular Tumoral , DNA/análise , Fluorescência , Humanos , Tamanho da Partícula , Reação em Cadeia da Polimerase/instrumentação , Propriedades de Superfície
9.
J Orthop Sci ; 23(5): 783-787, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29935972

RESUMO

BACKGROUND: The difference in clinical results between the direct anterior approach (DAA) and the anterolateral approach (ALA) for total hip arthroplasty (THA) is still unclear. The purpose of this study was to compare clinical results, including nerve injuries, between DAA and ALA in one-stage bilateral THA in a prospective, randomized controlled trial. METHODS: Thirty patients were recruited for primary bilateral THAs from 2014 to 2016. The left and right hips of each patient were randomly assigned to DAA and the others to ALA. We prospectively compared the clinical results, incidence of lateral femoral cutaneous nerve (LFCN) injury, and tensor fascia lata (TFL) atrophy considered to be related to superior gluteal nerve injury between both approaches. RESULTS: No significant difference was found in the clinical results between both sides at postoperative 1 year. Temporary symptom of LFCN injury was observed only in DAA sides (7/30, 23.3%). The ratio of 3-month postoperative to preoperative cross-sectional area of TFL on computed tomography was significantly lower on the side subjected to DAA (DAA side, 78.8 ± 22.8%) than on the side subjected to ALA (ALA side, 90.7 ± 17.7%) (p < 0.01). In magnetic resonance imaging at postoperative 1 year, the mean grade of fatty atrophy of TFL by Goutalier classification was significantly higher in DAA sides (2.00 ± 1.6) than in ALA sides (1.1 ± 1.3) (p = 0.03). CONCLUSIONS: Excellent clinical results for both DAA and ALA were achieved. LFCN injury was found only in DAA sides. Although TFL atrophy was found in both approaches, it was found significantly more in DAA sides. Our study suggested that ALA should be used rather than DAA in terms of the risk of nerve injuries.


Assuntos
Artroplastia de Quadril/métodos , Nervo Femoral/lesões , Osteoartrite do Quadril/cirurgia , Posicionamento do Paciente , Traumatismos dos Nervos Periféricos/etiologia , Complicações Pós-Operatórias/etiologia , Idoso , Artroplastia de Quadril/efeitos adversos , Atrofia , Nádegas/inervação , Fascia Lata/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos dos Nervos Periféricos/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos , Decúbito Dorsal
10.
Eur J Orthop Surg Traumatol ; 28(4): 621-625, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29299764

RESUMO

PURPOSE: The purpose of this study is to clarify morphological changes of acetabular subchondral bone cyst after total hip arthroplasty for osteoarthritis secondary to developmental dysplasia of the hip. METHODS: Two hundred and sixty-one primary cementless total hip arthroplasties of 208 patients, 18 males, 190 females, were retrospectively reviewed. Morphological changes of subchondral bone cyst were evaluated by computed tomography (CT). The mean cross-sectional area of the cyst from CT scans at 3 months postoperatively and after 7-10 years (average 8.4 years) were compared. RESULTS: Acetabular subchondral bone cysts were found in 49.0% of all cases in preoperative CT scans. There was no cyst which was newly recognized in CT scan performed after postoperative 7-10 years. All the cross-sectional areas of the cysts evaluated in this study were reduced postoperatively. CONCLUSIONS: This study revealed that acetabular subchondral bone cysts do not increase or expand after total hip arthroplasty and indicated that the longitudinal morphological change of acetabular bone cysts in patients of developmental dysplasia of the hip do not influence long-term implant fixation in total hip arthroplasty.


Assuntos
Acetábulo/patologia , Artroplastia de Quadril/métodos , Cistos Ósseos/patologia , Luxação Congênita de Quadril/complicações , Osteoartrite do Quadril/cirurgia , Acetábulo/diagnóstico por imagem , Cistos Ósseos/diagnóstico por imagem , Feminino , Luxação Congênita de Quadril/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/etiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
11.
J Arthroplasty ; 32(2): 594-600, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27554784

RESUMO

BACKGROUND: Femurs of dysplastic hips exhibit specific abnormalities, and use of modular or specially designed components is recommended. An anatomic short stem was previously designed specifically for dysplastic hips using 3-dimensional data acquired from dysplastic patients. To investigate effects of stem geometry on bone remodeling, we undertook a prospective, randomized study of patients who had undergone 1-stage bilateral total hip arthroplasty (THA) with the anatomic short stem on one side and a conventional straight stem on the other. METHODS: The study included 36 patients who underwent the above THA procedure. We assessed bone mineral density as well as the presence of cancellous condensation or bony atrophy due to stress shielding based on the analysis of Gruen's zones and newly defined equal-interval zones, at an average follow-up period of 9.2 years. RESULTS: All stems were bone ingrown stable. Cancellous condensation was observed more proximally, and areas of bone atrophy were narrower on the anatomic short stem side than on the straight stem side. Bone mineral density values reflected results of cancellous condensation and stress shielding and were higher in more proximal zones on the anatomic short stem side than on the straight stem side. CONCLUSION: Although radiographic results indicated good midterm outcomes of THA with both stems, the loading pattern differed. The anatomic short stem achieved its design purpose in terms of proximal fixation and load transfer and led to better preservation of the proximal femur.


Assuntos
Artroplastia de Quadril/instrumentação , Remodelação Óssea , Luxação Congênita de Quadril/cirurgia , Prótese de Quadril , Idoso , Densidade Óssea , Osso e Ossos/cirurgia , Feminino , Fêmur/cirurgia , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
J Arthroplasty ; 32(5): 1547-1552, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28110848

RESUMO

BACKGROUND: Appropriate stem anteversion is important for achieving stability of the prosthetic joint in total hip arthroplasty. Anteversion of a cementless femoral stem is affected by the femoral canal morphology and varies according to stem geometry. We investigated the difference and variation of the increase in anteversion between 2 types of cementless stems, and the correlation between each stem and the preoperative femoral anteversion. METHODS: We retrospectively compared 2 groups of hips that underwent total hip arthroplasty using a metaphyseal filling stem (78 hips) or a tapered wedge stem (83 hips). All the patients had osteoarthritis due to hip dysplasia. Computed tomography was used to measure preoperative femoral anteversion at 5 levels and postoperative stem anteversion. RESULTS: The increase in anteversion of the tapered wedge stem group (22.7° ± 11.6°) was more than that of the metaphyseal filling stem group (17.2° ± 8.3°; P = .0007). The variation of the increase in the tapered wedge stem group was significantly larger than that in the metaphyseal filling stem group (P = .0016). The metaphyseal filling stem group was more highly and positively correlated with femoral anteversion than the tapered wedge stem group. CONCLUSION: Femoral anteversion affects stem anteversion differently according to stem geometry. The tapered wedge stems had greater variation of the increase in anteversion than did the metaphyseal filling stems. Based on the results of this study, it is difficult to preoperatively estimate the increase in stem anteversion for tapered wedge stems.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Mau Alinhamento Ósseo/prevenção & controle , Luxação Congênita de Quadril/cirurgia , Prótese de Quadril , Osteoartrite do Quadril/cirurgia , Idoso , Artroplastia de Quadril/instrumentação , Cimentos Ósseos , Mau Alinhamento Ósseo/etiologia , Cimentação , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Luxação Congênita de Quadril/complicações , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/etiologia , Desenho de Prótese , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Clin Exp Nephrol ; 20(3): 450-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26463736

RESUMO

BACKGROUND: Aquaporin-2 (AQP2) in urine is now measured in many water-balance disorders and regarded as a useful biomarker for diagnosis and prognosis. An enzyme-linked immunosorbent assay (ELISA) method has been developed for measurement of large numbers of clinical samples. However, fluctuations in the measured values were sometimes observed depending on storage conditions. Urine AQP2 is present in exosome membranes and we speculated that this structural organization causes the fluctuations. METHODS: Human urine samples from healthy subjects were measured by ELISA. Effects of maneuvers to disrupt the exosome membrane mechanically (freezing and thawing at different temperatures) and chemically (treating with alkali and detergents) prior to ELISA were examined. RESULTS: Urine samples stored at 4 or -80 °C did not show significant AQP2 values, whereas those stored at -25 °C for more that 2 weeks provided the values. Urine samples treated with 0.4 N NaOH and 0.5 % Triton X-305 showed the consistent and comparable values to those stored at -25 °C. CONCLUSION: Pretreatment with alkali (0.4 N NaOH) to disrupt exosome membranes allowed consistent ELISA measurements of urinary AQP2. This simple method is applicable to ELISA of other membrane proteins included in exosomes.


Assuntos
Álcalis/química , Aquaporina 2/urina , Ensaio de Imunoadsorção Enzimática , Exossomos/química , Hidróxido de Sódio/química , Manejo de Espécimes/métodos , Urinálise/métodos , Biomarcadores/urina , Temperatura Baixa , Ensaio de Imunoadsorção Enzimática/normas , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Fatores de Tempo , Urinálise/normas
14.
Undersea Hyperb Med ; 43(7): 847-854, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28777523

RESUMO

INTRODUCTION: Transient osteoporosis of the hip (TOH) is a self-limiting disorder characterized by bone marrow edema at the femoral head and neck. Patients report pain as moderate or severe at onset; pain gradually subsides at about six months (range four to 12 months). Differential diagnosis of the early stages of osteonecrosis of the femoral head (ONFH) is sometimes difficult. Because hyperbaric oxygen (HBO2) therapy is effective for reduction of edema in soft tissue injury and early stages of ONFH, we hypothesized that HBO2 could be effective in TOH for accelerated recovery. METHODS: Five cases of TOH treated with HBO2 were clinically evaluated. HBO2 was started from three to eight weeks after onset and performed four or five times a week, averaging a total of 27.8 ± 4.7 treatments (range 20-32). Clinical features were evaluated repeatedly with clinical examination, subjective evaluation of pain, and imaging methods that included magnetic resonance imaging (MRI) and bone scans. RESULTS: The average time to return-to-normal hip range of motion was 15.4 ± 7.8 weeks after onset, and relief of subjective pain was 16.6 ± 4.0 weeks. The average time to return-to-normal signal level in MRI was 22.0 ± 2.5 weeks, which was one to two months after relief of subjective pain. COMCLUSIONS: Multiple HBO2 treatments have the possibility of contributing to recovery acceleration in patients with TOH. However, in this study, we found that HBO2 treatment did not significantly accelerate the recovery of these five patients with TOH. The use of HBO2 should therefore be limited to patients in whom the differential diagnosis between TOH and early stage ONFH cannot be established.


Assuntos
Cabeça do Fêmur , Colo do Fêmur , Oxigenoterapia Hiperbárica , Osteoporose/terapia , Adulto , Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/diagnóstico , Colo do Fêmur/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Fatores de Tempo
15.
Mod Rheumatol ; 26(5): 757-60, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26708312

RESUMO

OBJECTIVES: The purpose of this retrospective study is to report the incidence of osteolysis and evaluate the significance of screening computed tomography (CT) compared to plain radiography in detecting osteolysis after total hip arthroplasty with metal-on-highly cross-linked polyethylene bearings. METHODS: We retrospectively reviewed 264 primary cementless total hip arthroplasties of 211 patients, 24 males, 187 females, who received postoperative screening CT scan in addition to radiography at postoperative 7-10 years (average 8.2 years). First-generation highly cross-linked polyethylene was used in all cases. RESULTS: On the plain radiographs, no acetabular osteolysis (0%) and two cases of femoral osteolysis (0.8%) were found in the follow-up period. No osteolysis was newly found by screening CT scan. CONCLUSIONS: Very low incidence of osteolysis after total hip arthroplasty with highly cross-linked polyethylene at postoperative 7-10 years was confirmed, and routine screening CT scan for detecting osteolysis in this setting was not supported from this study.


Assuntos
Acetábulo/diagnóstico por imagem , Artroplastia de Quadril/efeitos adversos , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril/efeitos adversos , Osteólise/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Acetábulo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Polietileno , Desenho de Prótese , Falha de Prótese , Estudos Retrospectivos , Adulto Jovem
16.
Biochem Biophys Res Commun ; 466(3): 319-26, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26362183

RESUMO

Osteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 ± HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA.


Assuntos
Envelhecimento , Regulação da Expressão Gênica , Síndrome Metabólica/genética , Osteoartrite/genética , Sirtuínas/fisiologia , Animais , Apoptose , Cartilagem Articular/patologia , Senescência Celular , Condrócitos/citologia , Condrócitos/metabolismo , Progressão da Doença , Perfilação da Expressão Gênica , Intolerância à Glucose , Teste de Tolerância a Glucose , Glicosaminoglicanos/química , Hipertrofia , Inflamação/genética , Inflamação/metabolismo , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Transgênicos , Osteoartrite/metabolismo , Osteófito/metabolismo , Serpina E2/metabolismo , Sirtuínas/genética
17.
PLoS Genet ; 8(9): e1002957, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23028364

RESUMO

Reactive oxygen species (ROS) are toxic but essential molecules responsible for host defense and cellular signaling. Conserved NADPH oxidase (NOX) family enzymes direct the regulated production of ROS. Hydrogen peroxide (H(2)O(2)) generated by dual oxidases (DUOXs), a member of the NOX family, is crucial for innate mucosal immunity. In addition, H(2)O(2) is required for cellular signaling mediated by protein modifications, such as the thyroid hormone biosynthetic pathway in mammals. In contrast to other NOX isozymes, the regulatory mechanisms of DUOX activity are less understood. Using Caenorhabditis elegans as a model, we demonstrate that the tetraspanin protein is required for induction of the DUOX signaling pathway in conjunction with the dual oxidase maturation factor (DUOXA). In the current study, we show that genetic mutation of DUOX (bli-3), DUOXA (doxa-1), and peroxidase (mlt-7) in C. elegans causes the same defects as a tetraspanin tsp-15 mutant, represented by exoskeletal deficiencies due to the failure of tyrosine cross-linking of collagen. The deficiency in the tsp-15 mutant was restored by co-expression of bli-3 and doxa-1, indicating the involvement of tsp-15 in the generation of ROS. H(2)O(2) generation by BLI-3 was completely dependent on TSP-15 when reconstituted in mammalian cells. We also demonstrated that TSP-15, BLI-3, and DOXA-1 form complexes in vitro and in vivo. Cell-fusion-based analysis suggested that association with TSP-15 at the cell surface is crucial for BLI-3 activation to release H(2)O(2). This study provides the first evidence for an essential role of tetraspanin in ROS generation.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans , Peróxido de Hidrogênio/metabolismo , Proteínas de Membrana , Oxirredutases , Animais , Células COS , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Chlorocebus aethiops , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Oxirredutases/genética , Oxirredutases/metabolismo , Peroxidase/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Tetraspaninas
18.
J Arthroplasty ; 30(1): 74-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25216791

RESUMO

One-stage primary bilateral cementless total hip arthroplasty with unilateral closed suction drainage (CSD) was prospectively performed for 51 patients (102 hips), and local effects of CSD were quantitatively evaluated. Postoperatively, pain scores evaluated by visual analog scale and periwound temperatures measured by thermography were lower in the CSD side than the non-CSD side. CT measurements also showed that postoperative cross-sectional area of the thigh was smaller in the CSD side. Active straight leg raising and weight bearing were more accelerated in the CSD side., showing earlier recovery of hip joint function. CSD for hip arthroplasty has an advantage in reducing postoperative local inflammation and be recommended from the viewpoint of postoperative pain relief and early recovery of hip joint function.


Assuntos
Artroplastia de Quadril/métodos , Articulação do Quadril/cirurgia , Osteoartrite do Quadril/cirurgia , Sucção , Adulto , Temperatura Corporal , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica
19.
J Arthroplasty ; 30(12): 2237-41, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26190568

RESUMO

To evaluate the mid-term effects of different materials and coatings used for femoral components, we prospectively performed 21 one-stage bilateral total hip arthroplasties using 2 anatomical stems which have identical geometries, randomized to side. One stem was made of Ti6Al4V alloy and had a hydroxyapatite coating on grit-blasted surface proximally, and the other was made of TMZF™ alloy and had a proximal coating of hydroxyapatite in addition to an arc-deposited titanium surface coating. Although we found extensions of radiopaque lines to the surface of coatings of seven grit-blasted stems whereas we found none in the case of the arc-deposited titanium stems, all hips showed excellent clinical and radiological outcomes as shown by radiographs and bone mineral density at the final follow-up, average 5.5 years postoperatively.


Assuntos
Ligas , Artroplastia de Quadril/instrumentação , Materiais Revestidos Biocompatíveis , Prótese de Quadril/estatística & dados numéricos , Titânio , Adolescente , Adulto , Densidade Óssea , Durapatita , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Adulto Jovem
20.
J Arthroplasty ; 30(8): 1407-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25770862

RESUMO

The purpose of this study was to evaluate a prognostic value of drain tip culture for surgical site infection (SSI) after total hip arthroplasty. A total of 1380 closed suction drain tips cultured after removal in primary total hip arthroplasty were included in this study. Drains were removed in 12-72 hours after surgery. Drain tip cultures were positive in 11 cases (0.8%). SSI was found in 4 cases (0.3%), where the drain tip cultures were all negative. The sensitivity of drain tip culture for infection after surgery was 0%, and the specificity was 99.7%. We concluded that, drain tip culture cannot be prognostic for SSI after total hip arthroplasty. Routine use of drain tip culture is not supported.


Assuntos
Artroplastia de Quadril , Infecções Relacionadas à Prótese/microbiologia , Sucção/instrumentação , Infecção da Ferida Cirúrgica/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Bacteriológicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
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