RESUMEN
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.
Asunto(s)
Síndrome de Creutzfeldt-Jakob , Enfermedades por Prión , Priones , Animales , Ratones , Humanos , Proteínas Priónicas/genética , Mutación Puntual , Glicosilfosfatidilinositoles/genética , Glicosilfosfatidilinositoles/metabolismo , Señales de Clasificación de Proteína/genética , Enfermedades por Prión/genética , Enfermedades por Prión/patología , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patología , Priones/genética , Priones/metabolismo , Mutación/genéticaRESUMEN
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.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Endosomas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Microfilamentos/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Transporte Biológico , Línea Celular , Endocitosis/genética , Células HEK293 , Células HeLa , Humanos , Lisosomas/metabolismo , Proteínas de la Membrana/genética , Proteínas de Microfilamentos/genética , Unión Proteica , Mapeo de Interacción de Proteínas , Transferrina/genética , Transferrina/metabolismo , Ubiquitinación , Proteínas de Transporte Vesicular/genética , Proteínas de Unión al GTP rab/genéticaRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Artroplastia de Reemplazo de Cadera/efectos adversos , Densidad Ósea , Fémur/cirugía , Humanos , Estudios Prospectivos , Diseño de PrótesisRESUMEN
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.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Corazón/efectos de los fármacos , Miocardio/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Propanolaminas/uso terapéutico , Adenosina Trifosfato/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacología , Animales , Ácidos Grasos/metabolismo , Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/mortalidad , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/genéticaRESUMEN
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.
Asunto(s)
Neuronas Motoras/citología , Músculo Esquelético/inervación , Somitos/inervación , Nervios Espinales/embriología , Animales , Tipificación del Cuerpo , Embrión de Pollo , Coturnix , Músculo Esquelético/embriología , Tubo Neural , Somitos/embriología , Torso/embriología , Torso/inervaciónRESUMEN
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 24â 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.
Asunto(s)
Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Células Neuroendocrinas/metabolismo , Oxígeno/farmacología , Adenohipófisis/metabolismo , Proopiomelanocortina/biosíntesis , Regulación hacia Arriba/efectos de los fármacos , Animales , Técnicas de Cultivo de Célula , Línea Celular , RatonesRESUMEN
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.
Asunto(s)
ADN/genética , Tinta , Papillomaviridae/genética , Reacción en Cadena de la Polimerasa , Impresión , Línea Celular Tumoral , ADN/análisis , Fluorescencia , Humanos , Tamaño de la Partícula , Reacción en Cadena de la Polimerasa/instrumentación , Propiedades de SuperficieRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Nervio Femoral/lesiones , Osteoartritis de la Cadera/cirugía , Posicionamiento del Paciente , Traumatismos de los Nervios Periféricos/etiología , Complicaciones Posoperatorias/etiología , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Atrofia , Nalgas/inervación , Fascia Lata/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de los Nervios Periféricos/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Estudios Prospectivos , Posición SupinaRESUMEN
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.
Asunto(s)
Acetábulo/patología , Artroplastia de Reemplazo de Cadera/métodos , Quistes Óseos/patología , Luxación Congénita de la Cadera/complicaciones , Osteoartritis de la Cadera/cirugía , Acetábulo/diagnóstico por imagen , Quistes Óseos/diagnóstico por imagen , Femenino , Luxación Congénita de la Cadera/patología , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/etiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo de Cadera/instrumentación , Remodelación Ósea , Luxación Congénita de la Cadera/cirugía , Prótesis de Cadera , Anciano , Densidad Ósea , Huesos/cirugía , Femenino , Fémur/cirugía , Articulación de la Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Desviación Ósea/prevención & control , Luxación Congénita de la Cadera/cirugía , Prótesis de Cadera , Osteoartritis de la Cadera/cirugía , Anciano , Artroplastia de Reemplazo de Cadera/instrumentación , Cementos para Huesos , Desviación Ósea/etiología , Cementación , Femenino , Fémur/diagnóstico por imagen , Fémur/cirugía , Luxación Congénita de la Cadera/complicaciones , Prótesis de Cadera/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/etiología , Diseño de Prótesis , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
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.
Asunto(s)
Álcalis/química , Acuaporina 2/orina , Ensayo de Inmunoadsorción Enzimática , Exosomas/química , Hidróxido de Sodio/química , Manejo de Especímenes/métodos , Urinálisis/métodos , Biomarcadores/orina , Frío , Ensayo de Inmunoadsorción Enzimática/normas , Voluntarios Sanos , Humanos , Concentración de Iones de Hidrógeno , Reproducibilidad de los Resultados , Factores de Tiempo , Urinálisis/normasRESUMEN
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.
Asunto(s)
Cabeza Femoral , Cuello Femoral , Oxigenoterapia Hiperbárica , Osteoporosis/terapia , Adulto , Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/diagnóstico , Cuello Femoral/diagnóstico por imagen , Articulación de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico , Rango del Movimiento Articular , Recuperación de la Función , Factores de TiempoRESUMEN
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.
Asunto(s)
Acetábulo/diagnóstico por imagen , Artroplastia de Reemplazo de Cadera/efectos adversos , Articulación de la Cadera/diagnóstico por imagen , Prótesis de Cadera/efectos adversos , Osteólisis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Acetábulo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Articulación de la Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Polietileno , Diseño de Prótesis , Falla de Prótesis , Estudios Retrospectivos , Adulto JovenRESUMEN
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.
Asunto(s)
Envejecimiento , Regulación de la Expresión Génica , Síndrome Metabólico/genética , Osteoartritis/genética , Sirtuinas/fisiología , Animales , Apoptosis , Cartílago Articular/patología , Senescencia Celular , Condrocitos/citología , Condrocitos/metabolismo , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Glicosaminoglicanos/química , Hipertrofia , Inflamación/genética , Inflamación/metabolismo , Síndrome Metabólico/metabolismo , Ratones , Ratones Transgénicos , Osteoartritis/metabolismo , Osteofito/metabolismo , Serpina E2/metabolismo , Sirtuinas/genéticaRESUMEN
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.
Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans , Peróxido de Hidrógeno/metabolismo , Proteínas de la Membrana , Oxidorreductasas , Animales , Células COS , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Chlorocebus aethiops , Células HeLa , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Peroxidasa/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , TetraspaninasRESUMEN
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.
Asunto(s)
Aleaciones , Artroplastia de Reemplazo de Cadera/instrumentación , Materiales Biocompatibles Revestidos , Prótesis de Cadera/estadística & datos numéricos , Titanio , Adolescente , Adulto , Densidad Ósea , Durapatita , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Adulto JovenRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Infecciones Relacionadas con Prótesis/microbiología , Succión/instrumentación , Infección de la Herida Quirúrgica/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Técnicas Bacteriológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Articulación de la Cadera/cirugía , Osteoartritis de la Cadera/cirugía , Succión , Adulto , Temperatura Corporal , Femenino , Calor , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/fisiopatología , Estudios Prospectivos , Recuperación de la FunciónRESUMEN
Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused by myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets of current antifibrotic drugs, no drug has yet been approved to stop fibrosis progression. Herein, we aimed to identify GPCRs with profibrotic effects. In gene expression analysis of mouse lungs with induced fibrosis, eight GPCRs were identified, showing a >2-fold increase in mRNA expression after fibrosis induction. Among them, we focused on Gpr176 owing to its significant correlation with a myofibroblast marker α-smooth muscle actin (αSMA), the profibrotic factor transforming growth factor ß1 (TGFß1), and collagen in a human lung gene expression database. Similar to the lung fibrosis model, increased Gpr176 expression was also observed in other organs affected by fibrosis, including the kidney, liver, and heart, suggesting its role in fibrosis across various organs. Furthermore, fibroblasts abundantly expressed Gpr176 compared to alveolar epithelial cells, endothelial cells, and macrophages in the fibrotic lung. GPR176 expression was unaffected by TGFß1 stimulation in rat renal fibroblast NRK-49 cells, whereas knockdown of Gpr176 by siRNA reduced TGFß1-induced expression of αSMA, fibronectin, and collagen as well as Smad2 phosphorylation. This suggested that Gpr176 regulates fibroblast activation. Consequently, Gpr176 acts in a profibrotic manner, and inhibiting its activity could potentially prevent myofibroblast differentiation and improve fibrosis. Developing a GPR176 inverse agonist or allosteric modulator is a promising therapeutic approach for fibrosis.