RESUMEN
Currently, the role of transient receptor potential vanilloid type 4 (TRPV4), a nonselective cation channel in the pathology of spinal cord injury (SCI), is not recognized. Herein, we report the expression and contribution of TRPV4 in the pathology of scarring and endothelial and secondary damage after SCI. TRPV4 expression increased during the inflammatory phase in female rats after SCI and was expressed primarily by cells at endothelial-microglial junctions. Two-photon microscopy of intracellular-free Ca2+ levels revealed a biphasic increase at similar time points after SCI. Expression of TRPV4 at the injury epicenter, but not intracellular-free Ca2+, progressively increases with the severity of the injury. Activation of TRPV4 with specific agonist altered the organization of endothelial cells, affected tight junctions in the hCMEC/D3 BBB cell line in vitro, and increases the scarring in rat spinal cord as well as induced endothelial damage. By contrast, suppression of TRPV4 with a specific antagonist or in female Trpv4 KO mouse attenuated inflammatory cytokines and chemokines, prevented the degradation of tight junction proteins, and preserve blood-spinal cord barrier integrity, thereby attenuate the scarring after SCI. Likewise, secondary damage was reduced, and behavioral outcomes were improved in Trpv4 KO mice after SCI. These results suggest that increased TRPV4 expression disrupts endothelial cell organization during the early inflammatory phase of SCI, resulting in tissue damage, vascular destabilization, blood-spinal cord barrier breakdown, and scarring. Thus, TRPV4 inhibition/knockdown represents a promising therapeutic strategy to stabilize/protect endothelial cells, attenuate nociception and secondary damage, and reduce scarring after SCI.SIGNIFICANCE STATEMENT TRPV4, a calcium-permeable nonselective cation channel, is widely expressed in both excitable and nonexcitable cells. Spinal cord injury (SCI) majorly caused by trauma/accidents is associated with changes in osmolarity, mechanical injury, and shear stress. After SCI, TRPV4 was increased and were found to be linked with the severity of injury at the epicenter at the time points that were reported to be critical for repair/treatment. Activation of TRPV4 was damaging to endothelial cells that form the blood-spinal cord barrier and thus contributes to scarring (glial and fibrotic). Importantly, inhibition/knockdown of TRPV4 prevented these effects. Thus, the manipulation of TRPV4 signaling might lead to new therapeutic strategies or combinatorial therapies to protect endothelial cells and enhance repair after SCI.
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Endotelio/patología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Médula Espinal/patología , Canales Catiónicos TRPV/metabolismo , Animales , Conducta Animal , Quimiocinas/metabolismo , Citocinas/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Locomoción , Ratones , Ratones Noqueados , Microglía/metabolismo , Microglía/patología , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/psicología , Canales Catiónicos TRPV/genética , Uniones Estrechas/metabolismo , Uniones Estrechas/patologíaRESUMEN
In this study, we created a hydrogel composed of glycol chitosan (gC) and oxidized hyaluronate (oHA). Gold nanoparticles (GNPs) were conjugated with ursodeoxycholic acid (UDCA). The GNP-UDCA complex was embedded into gC-oHA (CHA) hydrogels to form a CHA-GNP-UDCA gel. This CHA-GNP-UDCA gel was injected once into an epicenter of an injured region in SCI rats. Near-infrared (NIR) irradiation was then applied to the lesion as a means of local therapy. To optimize the viscosity for injection into a lesion, several volume ratios of gC and oHA were investigated using scanning electron microscopy and a rotating rheometer. The optimally synthesized CHA-GNP-UDCA gel under NIR irradiation suppressed the production of inflammatory cytokines in vitro. In addition, the optimized CHA-GNP-UDCA gel under NIR irradiation inhibited the cystic cavity of the lesion and significantly improved the hindlimb function. The production of inflammatory cytokines following SCI was significantly inhibited in the CHA-GNP-UDCA gel + NIR group. CHA-GNP-UDCA gels with NIR irradiation can therefore have therapeutic effects for those with spinal cord injuries.
Asunto(s)
Nanopartículas del Metal , Traumatismos de la Médula Espinal , Animales , Oro , Hidrogeles/uso terapéutico , Inyecciones , Ratas , Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
Osseointegration is important in osteopenia and osteoporosis patients due to their low bone densities. Gold nanoparticles (GNPs) are greatly beneficial materials as osteogenic agents. The aim of this study is to investigate osseointegration between bones and double layers of GNP-immobilized titanium (Ti) implants. The physicochemical properties of the Ti surface were evaluated by scanning electron microscopy, by atomic force microscopy, by means of the contact angle using water drops, and by x-ray photoelectron spectroscopy. Osteogenic differentiation of human bone-marrow-derived mesenchymal stem cells was analyzed and showed the higher values in double layers of GNP (GNP2) groups. In addition, we performed an in vivo study using hydroxyapatite (HA) and GNP2 spine pedicle screws in ovariectomized (OVX) and SHAM rabbits. Osseointegration parameters also showed higher values in GNP2 than in HA groups. These findings suggest that implants with double layers of GNPs can be a useful alternative in osteoporotic patients.
Asunto(s)
Durapatita/química , Oro/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Nanopartículas del Metal/química , Oseointegración/efectos de los fármacos , Titanio/química , Titanio/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Nanopartículas del Metal/ultraestructura , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Conejos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Due to the safety issues and poor engraftment of mesenchymal stem cell (MSC) implantation, MSC-derived exosomes have been spotlighted as an alternative therapy for spinal cord injury (SCI). However, insufficient productivity of exosomes limits their therapeutic potential for clinical application. Moreover, low targeting ability of unmodified exosomes is a critical obstacle for their further applications as a therapeutic agent. In the present study, we fabricated macrophage membrane-fused exosome-mimetic nanovesicles (MF-NVs) from macrophage membrane-fused umbilical cord blood-derived MSCs (MF-MSCs) and confirmed their therapeutic potential in a clinically relevant mouse SCI model (controlled mechanical compression injury model). MF-NVs contained larger quantity of ischemic region-targeting molecules compared to normal MSC-derived nanovesicles (N-NVs). The targeting molecules in MF-NVs, which were derived from macrophage membranes, increased the accumulation of MF-NVs in the injured spinal cord after the in vivo systemic injection. Increased accumulation of MF-NVs attenuated apoptosis and inflammation, prevented axonal loss, enhanced blood vessel formation, decreased fibrosis, and consequently, improved spinal cord function. Synthetically, we developed targeting efficiency-potentiated exosome-mimetic nanovesicles and present their possibility of clinical application for SCI.
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Exosomas , Células Madre Mesenquimatosas/citología , Traumatismos de la Médula Espinal/terapia , Animales , Antiinflamatorios no Esteroideos/farmacología , Apoptosis , Femenino , Sangre Fetal/citología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Macrófagos/citología , Fusión de Membrana , Ratones , Ratones Endogámicos C57BL , Nanoestructuras , Neovascularización Fisiológica , Fármacos Neuroprotectores/farmacología , Células PC12 , Células RAW 264.7 , Ratas , Médula Espinal/irrigación sanguínea , Médula Espinal/patología , Traumatismos de la Médula Espinal/patologíaRESUMEN
Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.
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Osteoporosis/tratamiento farmacológico , Ovariectomía/efectos adversos , Fragmentos de Péptidos/metabolismo , Procolágeno/metabolismo , Ácido Tauroquenodesoxicólico/administración & dosificación , Animales , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Metilprednisolona/efectos adversos , Ratones , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoporosis/etiología , Osteoporosis/metabolismo , Distribución Aleatoria , Ácido Tauroquenodesoxicólico/farmacología , Resultado del TratamientoRESUMEN
Human mesenchymal stem cell (hMSC)-derived exosomes have been spotlighted as a promising therapeutic agent for cell-free regenerative medicine. However, poor organ-targeting ability and insufficient therapeutic efficacy of systemically injected hMSC-exosomes were identified as critical limitations for their further applications. Therefore, in this study we fabricated iron oxide nanoparticle (IONP)-incorporated exosome-mimetic nanovesicles (NV-IONP) from IONP-treated hMSCs and evaluated their therapeutic efficacy in a clinically relevant model for spinal cord injury. Compared to exosome-mimetic nanovesicles (NV) prepared from untreated hMSCs, NV-IONP not only contained IONPs which act as a magnet-guided navigation tool but also carried greater amounts of therapeutic growth factors that can be delivered to the target cells. The increased amounts of therapeutic growth factors inside NV-IONP were attributed to IONPs that are slowly ionized to iron ions which activate the JNK and c-Jun signaling cascades in hMSCs. In vivo systemic injection of NV-IONP with magnetic guidance significantly increased the amount of NV-IONP accumulating in the injured spinal cord. Accumulated NV-IONP enhanced blood vessel formation, attenuated inflammation and apoptosis in the injured spinal cord, and consequently improved spinal cord function. Taken together, these findings highlight the development of therapeutic efficacy-potentiated extracellular nanovesicles and demonstrate their feasibility for repairing injured spinal cord.
Asunto(s)
Nanopartículas de Magnetita/química , Células Madre Mesenquimatosas/química , Traumatismos de la Médula Espinal/terapia , Animales , Apoptosis , Materiales Biomiméticos , Portadores de Fármacos/química , Liberación de Fármacos , Exosomas/química , Humanos , Péptidos y Proteínas de Señalización Intercelular/química , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/ultraestructura , Ratones , Neovascularización Fisiológica , Células PC12 , Ratas , Transducción de Señal , Traumatismos de la Médula Espinal/patologíaRESUMEN
BACKGROUND: The purpose of this nationwide age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in ankylosing spondylitis (AS). METHODS: The data in this study, spanning from January 1, 2010 to December 31, 2014, was obtained from a database maintained by the Korean National Health Insurance Service. A total of 12,988 patients with a diagnosis of AS were enrolled. The control group consisted of 64,940 age-sex-stratified matching subjects without AS. The 6year ischemic stroke incidence rate for each group was calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke. RESULTS: During the follow-up period, 73 patients (0.56%) in the AS group and 250 patients (0.38%) in the control group developed ischemic stroke (p = 0.0041). The hazard ratio of ischemic stroke in the AS group was 1.46 (95% confidence interval [95% CI], 1.13-1.90) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the AS group was 1.35 (95% CI, 1.04-1.75) after controlling for demographics and comorbid medical disorders. According to subgroup analysis, in female and diabetes and non-hypertension and dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in AS patients than those in control group. CONCLUSION: Our nationwide longitudinal study suggests an increased risk of ischemic stroke in AS patients.
Asunto(s)
Isquemia Encefálica/epidemiología , Espondilitis Anquilosante/epidemiología , Accidente Cerebrovascular/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana EdadRESUMEN
The authors regret to state that an incorrect image was uploaded in Fig. 2. Please see a newly updated Fig. 2. All statements including Figure Legends are correct.
RESUMEN
Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.
Asunto(s)
Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Osteoporosis Posmenopáusica/genética , Fracturas Osteoporóticas/genética , Polimorfismo de Nucleótido Simple , Fracturas de la Columna Vertebral/genética , Timidilato Sintasa/genética , Regiones no Traducidas 3' , Anciano , Estudios de Casos y Controles , Femenino , Fracturas por Compresión/genética , Humanos , Persona de Mediana EdadRESUMEN
Advances in mesenchymal stem cells (MSCs) and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain) regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs) into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs), and type II collagen (COL2). RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2) with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y)-box 9 (SOX9) and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPß). Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.
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Huesos/fisiología , Cartílago/fisiología , Células Madre Mesenquimatosas/citología , Proteína Homóloga de Ras Enriquecida en el Cerebro/metabolismo , Regeneración/fisiología , Adipogénesis , Tejido Adiposo/citología , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Cartílago/citología , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Condrogénesis , Colágeno Tipo II/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Osteogénesis , Proteína Homóloga de Ras Enriquecida en el Cerebro/antagonistas & inhibidores , Proteína Homóloga de Ras Enriquecida en el Cerebro/genética , Factor de Transcripción SOX9/metabolismoRESUMEN
Although a founder variant of RNF213 4810G>A is a major genetic risk factor for moyamoya disease (MMD) in East Asians, the frequency and disease susceptibility of RNF213 variants remain largely unknown. This study investigated the mutation analysis of RNF213 (4448, 4810, 4863, and 4950) between Korean MMD and healthy controls. We performed a polymerase chain reaction-restriction fragment length polymorphism analysis. To identify the association between RNF213 gene polymorphisms and MMD disease, we performed statistical analyses such as multivariable logistic regression and Fisher's exact test. Genetic data from 117 MMD patients were analyzed and compared with 253 healthy controls. We assessed and compared single nucleotide polymorphisms of RNF213 (4448, 4810, 4863, and 4950) between MMD and control groups. We performed genome-wide association studies to investigate the genetic pathophysiology of MMD. Among the RNF213 variants (4448G>A, 4810G>A, 4863G>A, and 4950G>A), RNF213 4810G>A and 4950G>A variants were more frequent in MMD patients. In a subgroup analysis, the RNF213 4810G>A was more frequent in moyamoya disease, and the comparison with GG+AA genotype was also significantly different in moyamoya patients. These results confirm that RNF213 4810G>A and RNF213 4950G>A were more frequent in MMD patients. We have confirmed that RNF213 4810G>A and 4950G>A are strongly associated with Korean MMD in children and adults as well as for the ischemic and hemorrhagic types.
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Adenosina Trifosfatasas/genética , Alelos , Predisposición Genética a la Enfermedad , Enfermedad de Moyamoya/genética , Polimorfismo de Nucleótido Simple , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Grupos de Población/genética , República de Corea , Adulto JovenRESUMEN
Expansion of chondrocytes for repair of articular cartilage can lead to dedifferentiation, making it difficult to obtain a sufficient quantity of chondrocytes. Although previous studies have suggested that culture in a three-dimensional environment induces redifferentiation of dedifferentiated chondrocytes, its underlying mechanisms are still poorly understood in terms of metabolism compared with a two-dimensional environment. In this study, we demonstrate that attenuation of transglutaminase 2 (TG2), a multifunctional enzyme, stimulates redifferentiation of dedifferentiated chondrocytes. Fibroblast-like morphological changes increased as TG2 expression increased in passage-dependent manner. When dedifferentiated chondrocytes were cultured in a pellet culture system, TG2 expression was reduced and glycolytic enzyme expression up-regulated. Previous studies demonstrated that TG2 influences energy metabolism, and impaired glycolytic metabolism causes chondrocyte dedifferentiation. Interestingly, TG2 knockdown improved chondrogenic gene expression, glycolytic enzyme expression, and lactate production in a monolayer culture system. Taken together, down-regulation of TG2 is involved in redifferentiaton of dedifferentiated chondrocytes through enhancing glucose metabolism.
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Diferenciación Celular/fisiología , Condrocitos/citología , Condrocitos/metabolismo , Condrogénesis/fisiología , Proteínas de Unión al GTP/metabolismo , Glucosa/metabolismo , Transglutaminasas/metabolismo , Diferenciación Celular/genética , Células Cultivadas , Condrogénesis/genética , Metabolismo Energético/genética , Metabolismo Energético/fisiología , Proteínas de Unión al GTP/genética , Humanos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas/genéticaRESUMEN
Osteoporosis and osteoporotic fractures are strongly associated with mortality and morbidity, both in developing and developed countries. Menopause accelerates bone loss due to estrogen deficiency and age-related linear bone loss. We investigated plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in postmenopausal women with osteoporotic vertebral compression fractures (OVCFs). In this case-control study, 355 postmenopausal women were genotyped for the presence of PAI-1 gene polymorphisms -844A > G, -675 4G > 5G, 43G > A, 9785A > G, and 11053T > G. Genetic polymorphisms of PAI-1 were analyzed by the polymerization chain reaction restriction fragment length polymorphism assay, and their association with disease status and folate and homocysteine levels was determined in 158 OVCF patients and 197 control subjects. The PAI-1 -675 5G5G (adjusted odds ratio (AOR), 3.302; p = 0.017) and 43GA + AA (AOR, 2.087; p = 0.042) genotype frequencies showed significant association with the increased prevalence of OVCFs in postmenopausal women. In addition, we performed gene-environment interaction studies and demonstrated an association between PAI-1 gene polymorphisms and OVCF prevalence. Our novel finding is the identification of several PAI-1 genetic variants that increase susceptibility to OVCF. Our findings suggest that polymorphisms in PAI-1 may contribute to OVCF, and that they can be developed as biomarkers for evaluating OVCF risk.
Asunto(s)
Fracturas por Compresión/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo Genético/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Fracturas por Compresión/patología , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos/genética , Humanos , Persona de Mediana Edad , Osteoporosis/genética , Osteoporosis/patología , PosmenopausiaRESUMEN
BACKGROUND: No previous reports have mentioned bone loss of the superior adjacent vertebra immediately posterior to the anterior flange of Bryan cervical disc (Medtronic Sofamor Danek, Memphis, TN, USA), which plays a central role to prevent posterior migration of the device. The purpose of this study is to describe a new potential complication, bone loss immediately posterior to the anterior total disc replacement (TDR) flange on the superior adjacent vertebra following the Bryan cervical TDR and to discuss the possible mechanism. METHODS: The authors retrospectively reviewed 37 patients undergoing cervical TDR with the Bryan cervical disc. The clinical and radiological outcome data were collected at 1, 3, 6, 12, 24, and 36 months postoperatively, and at last follow-up, which ranged from 42 to 113 moths (average, 60.1 months). Clinical evaluation included the visual analog scale and neck disability index, and the radiographic evaluation included measurements of the functional spinal unit range of motion on flexion and extension and identification of radiographic changes such as bone loss. RESULTS: The Bryan TDR showed good mid-term clinical and radiological outcomes. Interestingly, however, bone loss was noted immediately posterior to the TDR flange on superior adjacent vertebra in 3 total patients; at 3 months (n = 2) and 6 months (n = 1). Although the bone loss was increased up to 6 months, this did not progress and no degradation of clinical and radiological outcomes occurred at last follow-up. CONCLUSIONS: Bone loss immediately posterior to the anterior TDR flange on the superior adjacent vertebra can occur in the early postoperative period due to possibly stress shielding effect. However, it did not result in clinical changes or increased rates of graft failure at last follow-up. A long-term follow-up study is mandatory to evaluate the long-term effects of the bone loss.
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Enfermedades Óseas Metabólicas/etiología , Vértebras Cervicales/cirugía , Degeneración del Disco Intervertebral/etiología , Degeneración del Disco Intervertebral/cirugía , Prótesis Articulares , Complicaciones Posoperatorias/etiología , Reeemplazo Total de Disco/efectos adversos , Adulto , Vértebras Cervicales/diagnóstico por imagen , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Radiografía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To investigate the association of single-nucleotide polymorphisms (SNPs) in matrix metalloproteinases (MMPs)-2, -3, and -9 and tissue inhibitor of metalloproteinase (TIMP)-2 with moyamoya disease (MMD). We conducted a case-control study of MMD patients by assessing the prevalence of six SNPs of MMP-2 -1575G > A [rs243866], MMP-2 -1306C > T [rs243865], MMP-3 -1171 5a/6a [rs3025058], MMP-9 -1562C > T [rs3918242], MMP-9 Q279R [rs17576], and TIMP-2 -418G > C [rs8179090]. METHODS: Korean patients with MMD (n = 107, mean age, 20.9 ± 15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0 ± 16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. The genotyping of six well-known SNPs (MMP-2 -1575G > A, MMP-2 -1306C > T, MMP-3 -1171 5a/6a, MMP-9 -1562C > T, MMP-9 Q279R, and TIMP-2 -418G > C) in MMP and TIMP genes was performed by polymerase chain reaction-restriction fragment length polymorphism assays. RESULTS: A significantly higher frequency of the GC genotype for TIMP-2 -418 G > C was found in MMD patients. The MMP-9 Q279R GA + AA genotype showed a protective effect for MMD. The GA/CC MMP-2 -1575/-1306 genotype was significantly more prevalent in MMD patients. CONCLUSIONS: Our findings demonstrate that TIMP-2 -418 GC + CC and MMP-2 -1575GA/-1306CC genotypes could be genetic predisposing factors for MMD development.
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Metaloproteinasa 2 de la Matriz/genética , Enfermedad de Moyamoya/genética , Inhibidor Tisular de Metaloproteinasa-2/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Enfermedad de Moyamoya/epidemiología , Polimorfismo de Nucleótido Simple , Prevalencia , Regiones Promotoras Genéticas/genética , República de Corea/epidemiología , Adulto JovenRESUMEN
PURPOSE: The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms, which are associated with hyperhomocysteinemia and nitric oxide (NO) deficiency (which is related to atherothrombosis and cerebral ischemia), have not been studied in moyamoya disease. A case-control study was performed to investigate whether the MTHFR 677C>T and 1298A>C polymorphisms contribute to moyamoya disease (MMD). METHODS: One hundred and seven Korean patients with MMD (mean age, 20.85 ± 15.89 years; 66.4 % female) and 232 healthy control subjects (mean age, 23.99 ± 16.16 years; 56.8 % female) were included. Genotyping for the MTHFR 677C>T and 1298A>C polymorphisms and measurements of homocysteine, folate, vitamin B12, and NO in the cerebrospinal fluid (CSF) were performed. The statistical analysis was performed by multivariate linear regression and logistic regression. RESULT: The MTHFR 677CT+TT genotype frequency was significantly increased with early-onset MMD (<10 years) compared with late-onset MMD (≥10 years) (adjusted odds ratio, 3.392; 95 % confidence interval, 1.294-8.893, P = 0.013). The MTHFR 677C-1298C/677T-1298A diplotype (1.71 ± 1.23 arbitrary units) presented significantly lower NO levels in the CSF compared with the 677C-1298A/677C-1298A diplotype (11.40 ± 12.24 arbitrary units). CONCLUSION: The MTHFR 677C>T and 1298A>C polymorphisms have restricted roles in the Korean MMD population. Therefore, further studies involving larger and more heterogeneous cohorts are needed to extend our understanding of the influence of polymorphisms in MTHFR and other thrombophilic genes on MMD.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Enfermedad de Moyamoya/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Ácido Fólico/líquido cefalorraquídeo , Genotipo , Homocisteína/líquido cefalorraquídeo , Humanos , Modelos Lineales , Masculino , Enfermedad de Moyamoya/líquido cefalorraquídeo , Óxido Nítrico/líquido cefalorraquídeo , República de Corea , Vitamina B 12/líquido cefalorraquídeo , Adulto JovenRESUMEN
Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan-Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40-4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45-4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA.
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BACKGROUND: Abnormalities of bone metabolism may be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) of the spine. Besides its hemostatic effect, vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a pivotal role in bone mineralization. The aim of this study is to investigate whether single nucleotide polymorphisms (SNPs) of the VKORC1 gene are associated with the occurrence of OPLL in a Korean population. METHOD: A total of 98 patients with OPLL and 200 controls were genotyped for the VKORC1-1639G>A SNP (rs9923231) by polymerase chain reaction and restriction fragment length polymorphism analysis. All the patients (n = 98) in this study underwent surgery (60, posterior-only approach; 36, anterior-only approach; 2, combined anterior and posterior approach) during their admission. We analyzed this association separately according to the gender and OPLL subgroup: OPLL continuous group (continuous type plus mixed type) and OPLL segmental group (segmental and localized type). RESULTS: We found that the genotype VKORC1-1639G>A frequency was significantly associated with the occurrence of the OPLL in the female group (adjusted odds ratio = 5.22, 95 % confidence interval: 1.675 to 16.269, p = 0.004). However, there was no overall association between the OPLL susceptibility and VKORC1-1639G>A polymorphism. A subgroup analysis did not show any significant correlation between VKORC1-1639G>A polymorphism and subgroup of OPLL either. CONCLUSION: Our results suggest that the VKORC1-1639G>A SNP may increase susceptibility to OPLL in women. However, there was only a statistical association in the female group despite a number of stratified analyses. Therefore, the findings should be interpreted with caution, and further genetic study is needed to improve our understanding of the role of VKORC1 polymorphisms in determining the risk of OPLL occurrence.
Asunto(s)
Predisposición Genética a la Enfermedad , Osificación del Ligamento Longitudinal Posterior/genética , Polimorfismo de Nucleótido Simple/genética , Vitamina K Epóxido Reductasas/genética , Adulto , Anciano , Pueblo Asiatico/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Osificación del Ligamento Longitudinal Posterior/etiología , Factores SexualesRESUMEN
OBJECTIVE: The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. METHODS: From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. RESULTS: According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age <65, age >65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). CONCLUSIONS: The risk rate of IS increased in patient with pyogenic spondylitis.
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BACKGROUND: Trigeminal neuralgia (TN) is primarily diagnosed by symptoms and patient history. Magnetic resonance (MR) imaging can be helpful in visualizing the neurovascular compression of the trigeminal nerve in TN patients, but the current parameters used as diagnostic markers for TN are less than optimal. The aim of this study is to assess whether the angle between the trigeminal nerve and the pons (the trigeminal-pontine angle) on the affected side of patients with idiopathic TN differs from that of the unaffected side and that found in controls without TN. METHODS: A case-control study of 30 clinically diagnosed idiopathic TN patients aged 30 to 79 years and 30 age- and sex-matched controls was conducted. We compared the trigeminal-pontine angle and trigeminal nerve atrophy via fast-imaging employing steady-state acquisition (FIESTA) MR imaging. RESULTS: A sharp trigeminal-pontine angle was observed in 25 patients (25/30) on the affected side. As such, the mean angle of the trigeminal nerve on the affected side (40.17) was significantly smaller than that on the unaffected side (48.91, p = 0.001) and that in the control group (52.02, p < 0.001). CONCLUSIONS: A sharp trigeminal-pontine angle on the affected side was found in idiopathic TN patients by FIESTA imaging. This suggests that a sharp trigeminal-pontine angle increases the chance of neurovascular compression on the medial side of the trigeminal nerve.