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1.
J Clin Orthop Trauma ; 23: 101621, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34692408

RESUMEN

Spinal surgery is becoming safer and progressively less invasive with advances in optical and instrument technology. The amount of decompression achievable with endoscopic approaches is now comparable to open approaches with the advantage of much less tissue trauma. This review aims at examining the status of endoscopic approaches in lumbar decompressive surgery.

2.
J Clin Orthop Trauma ; 22: 101609, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34631414

RESUMEN

Fully endoscopic cervical spine surgery is an emerging novel approach to address cervical spinal pathology. Techniques, both anterior and posterior have been adapted to address various cervical pathologies. The primary goal of these procedures like other open techniques is to surgically decompress the canal centrally and/or along the foramen. The narrative review aims to provide the reader an overview of the rapidly advancing field of endoscopic cervical spinal surgery and evaluate whether these newer approaches could potentially reduce the cost and the risk associated with instrumented cervical fusion.

3.
J Mech Behav Biomed Mater ; 118: 104473, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33773237

RESUMEN

Micro/nano-scale deformation behavior including hardness, elastic modulus, and pop-ins, was studied in a medical austenitic stainless steel followed by post-mortem EBSD characterization. Relatively higher hardness and modulus was observed near {101} and more pop-ins occurred in this orientation at high loading rate. The activation volume (v) obtained from nanoindentation had weak dependence on grain orientation and was ~10-20 b3, indicating that neither diffusional creep processes nor conventional dislocation segments passing through dislocation forests controls plastic deformation in our study. The plastic zone radius (c) and the distance of the indent from the grain boundary (d) were used to describe the effect of grain boundary on the pop-in effect. The ratio of c/d meets amplitude version of Gaussian peak function distribution for a given orientation, whose peak value remains nearly constant for all the orientations.


Asunto(s)
Acero Inoxidable , Módulo de Elasticidad , Dureza
4.
J Mech Behav Biomed Mater ; 119: 104489, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33780850

RESUMEN

The unique concept of phase reversion involving severe deformation of parent austenite into martensite, followed by annealing for a short duration, whereby the strain-induced martensite reverts to austenite, was adopted to obtain nano-grained/ultrafine-grained (NG/UFG) structure in a Cu-bearing biomedical austenitic stainless steel resulting in high strength-high ductility combination. Work hardening and accompanying deformation mechanism are two important aspects that govern the mechanical behavior of biomedical devices. Thus, post-mortem electron microscopy of the strained region was carried out to explore the differences in the deformation mechanisms induced by grain refinement, while the strain hardening behavior was analyzed by Crussard-Jaoul (C-J) analysis of the tensile stress-strain data. The strain hardening behavior consisted of four stages and was strongly affected by grain structure. Twinning-induced plasticity (TWIP) was the governing deformation mechanism in the NG/UFG structure and contributed to good ductility. In striking contrast, transformation-induced plasticity (TRIP) contributed to high ductility in the coarse-grained (CG) counterpart and was the governing strain hardening mechanism. When the grain size is less than ~1 µm, the increase in the strain energy and the austenite stability significantly reduce the possibility of strain-induced martensite transformation such that there is a distinct transition in deformation mechanism from nanoscale twinning in the NG/UFG structure to strain-induced martensite in CG structure. The differences in the deformation mechanisms are explained in terms of austenite stability - strain energy relationship.


Asunto(s)
Antiinfecciosos , Acero Inoxidable , Cobre , Aleaciones Dentales , Resistencia a la Tracción
5.
Bioact Mater ; 6(6): 1765-1776, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33313453

RESUMEN

Regeneration of long-bone segmental defects remains a challenge for orthopedic surgery. Current treatment options often require several revision procedures to maintain acceptable alignment and achieve osseous healing. A novel hollow tubular system utilizing magnesium-strontium (Mg-Sr) alloy with autogenous morselized bone filled inside to repair segmental defects was developed. To improve the corrosion and biocompatible properties, two coatings, Ca-P and Sr-P coatings, were prepared on surface of the implants. Feasibility of applying these coated implants was systematically evaluated in vitro and in vivo, and simultaneously to have a better understanding on the relationship of degradation and bone regeneration on the healing process. According to the in vitro corrosion study by electrochemical measurements, greater corrosion resistance was obtained for Ca-P coated sample, and attributed to the double-layer protective structure. The cytotoxicity and alkaline phosphatase (ALP) assays demonstrated enhanced bioactivity for Sr-P coated group because of the long-lasting release of beneficial Sr2+. At 12 weeks post-implantation with Mg-Sr alloy porous device, the segmental defects were effectively repaired with respect to both integrity and continuity. In addition, compared with the Ca-P coated implant, the Sr-P coated implant was more proficient at promoting bone formation and mineralization. In summary, the Sr-P coated implants have bioactive properties and exceptional durability, and promote bone healing that is close to the natural rate, implying their potential application for the regeneration of segmental defects.

6.
J Mech Behav Biomed Mater ; 108: 103815, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32469722

RESUMEN

The implant surface and tissue experience strain when micro-motion occurs at the bone-implant interface under physiological loading. Moreover, strain is also introduced on the surface during mechanical processing of biomedical devices. Both these situations can induce phase transformation depending on the degree of stability of the microstructural constituents. In this regard, we elucidate here the interplay between mechanically-induced phase transformation (strain-induced martensite) in austenitic stainless steel on osteoblast functions. Strain-induced martensite significantly impacted cellular functions, notably, cell attachment, cell-surface interactions, proliferation, and synthesis of prominent proteins (fibronectin, actin, and vinculin). Strain-induced martensite favorably modulated cellular activity and contributed to small differences in hydrophilicity in relation to the non-strained austenitic stainless steel surface. The study provides a pathway for tuning biological functionality via microstructural control facilitated by mechanical strain.


Asunto(s)
Prótesis e Implantes , Acero Inoxidable , Comunicación Celular
7.
J Crohns Colitis ; 14(8): 1090-1102, 2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32119090

RESUMEN

BACKGROUND AND AIMS: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. METHODS: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. RESULTS: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. CONCLUSIONS: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.


Asunto(s)
Adalimumab , Ácidos y Sales Biliares/análisis , Enfermedad de Crohn , Cisteína/análisis , Histidina/análisis , Inflamación , Infliximab , Metabolismo de los Lípidos/efectos de los fármacos , ARN Ribosómico 16S/análisis , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Adulto , Biomarcadores Farmacológicos/análisis , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/inmunología , Heces , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/orina , Infliximab/administración & dosificación , Infliximab/efectos adversos , Londres , Estudios Longitudinales , Masculino , Metabolómica/métodos , Valor Predictivo de las Pruebas , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Inhibidores del Factor de Necrosis Tumoral/efectos adversos
8.
J Mech Behav Biomed Mater ; 104: 103666, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32174424

RESUMEN

The ingenious concept of phase reversion annealing involving cold deformation of parent austenite to strain-induced martensite, followed by annealing was used to obtain nano-grained/ultrafine-grained (NG/UFG) structure in a Cu-bearing biomedical austenitic stainless steel resulting in high strength-high ductility combination. Having employed the concept effectively, the primary objective of this study is to critically analyze the interplay between the load-controlled deformation response, strain-rate sensitivity and deformation mechanism of NG/UFG austenitic stainless steel via nanoscale deformation experiments and compare with its coarse-grained (CG) counterpart. The study demonstrated that the strain-rate sensitivity of NG/UFG was ~1.5 times that of the CG structure. Post-mortem electron microscopy of plastic zone surrounding the indents indicated that the active deformation mechanism was nanoscale twinning with typical characteristics of a network of intersecting twins in the NG/UFG structure, while strain-induced martensite transformation was the effective deformation mechanism for the CG structure. The fracture morphology was also different for the two steels, essentially ductile in nature, and was characterized by striations marking the line-up of voids in NG/UFG steel and microvoid coalescence in CG counterpart. The differences in deformation mechanisms between the NG/UFG and CG structure are attributed to the austenite stability - strain energy relationship. Furthermore, the presence of ~3 wt % Cu in austenitic stainless steel had somewhat moderate effect on strain-rate sensitivity and activation volume at similar level of grain size in its Cu-free counterpart. Specifically, in the NG/UFG structure, the nanoscale twin density was noticeably higher in Cu-bearing austenitic stainless steel as compared to Cu-free counterpart, as Cu is known to increase the stacking fault energy.


Asunto(s)
Cobre , Acero Inoxidable , Resistencia a la Tracción
9.
Materials (Basel) ; 13(3)2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-32023895

RESUMEN

Isothermal treatment affects the microstructural evolution and the precipitation behavior of high-strength low alloy (HSLA) steels. In this regard, thermal simulation of different isothermal treatment temperatures was adopted by using a thermomechanical simulator. The results showed that hardness reached the maximum value at 600 °C holding temperature, which was related to a finer grain structure and granular bainite. The strengthening effect of precipitates was remarkable due to the combination of small particle size and small interparticle spacing. It is presumed that the precipitation started after 600 s at 600 °C. Precipitation strengthening continued to exist, even though coarsening of ferrite grains led to softening phenomena when the specimen was isothermally held at 750 °C, which led to relatively high hardness. The precipitates were fcc (Ti, Nb) (N, C) particles, and belonged to MX-type precipitates. Average size of precipitates increased from 3.14 to 4.83 nm when the specimens were isothermally held between 600 °C and 800 °C. Interparticle spacing of precipitates also increased with increasing isothermal treatment temperatures. These led to a reduction in precipitation strengthening. At the same time the polygonal ferrite content increased and ferrite grain size got larger, such that the hardness decreased continuously.

10.
J Mech Behav Biomed Mater ; 101: 103433, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31539734

RESUMEN

Conventional coarse-grained (CG) biomedical austenitic stainless steel with grain size in the micrometer range was subjected to a novel phase reversion concept involving severe cold deformation, followed by annealing, when the cold deformed martensite reverts to austenite with grain size in the nanometer/ultrafine (NG/UFG) regime (~200-400 nm). The mechanical behavior of CG and NG/UFG steels was studied via load-controlled and displacement-controlled experiments using a nanoindentation technique with the aim to simulate micromotion. The plastic zone associated with the indentation-induced deformed region was characterized by post-mortem electron microscopy of the deformed region to elucidate the deformation mechanism. Nanoscale twinning was the deformation mechanism in steel with grain size in the NG/UFG regime, and contributed to the ductility of high strength steel. In contrast, strain-induced martensite contributed to the ductility of low strength CG steel with micrometer grain size. Interestingly, besides the differences in the mechanical behavior, the biological functions of the two steels were remarkably different. Higher cell attachment, proliferation and higher expression level of prominent proteins, fibronection, actin and vinculin were favored by a surface with grain size in the nanometer regime and was in striking contrast with the surface with micrometer grain size. This behavior is attributed to the differences in the fraction of grain boundaries that are high energy two-dimensional defects. The study advances our understanding of the mechanical behavior of biomaterials and their cellular functions.


Asunto(s)
Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Aleaciones Dentales/química , Fenómenos Mecánicos , Nanoestructuras/química , Acero Inoxidable/química , Adhesión Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos
11.
Materials (Basel) ; 12(18)2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31491984

RESUMEN

In this study, a 304/20MnSi stainless-steel clad rebar was prepared by single-pass compression process using the MMS-200 Thermal Mechanical Simulator. The impact of different degrees of deformation and deformation temperature on microstructure evolution and the mechanical properties of stainless steel clad rebars were investigated. The study indicated that with the increase of the degree of deformation, the content of pearlite in a carbon steel matrix was increased, and the grains refined. The metallurgical bonding of the bonded interface was formed under high temperature and high extrusion force. With the increase of the deformation temperature, more bainite was obtained on the side of carbon steel, and the grain size increased. The obvious diffusion of Fe, Cr and Ni elements near the bonding interface resulted in higher microhardness of the stainless steel side and smaller microhardness of the carbon steel side. Moreover, the engineering stress-strain curves obtained by the tensile test showed that the plastic deformation of stainless steel and carbon steel was more coordinated. With the increase of deformation temperature and the degree of deformation, the tensile strength of the stainless steel clad rebar was as high as 690 MPa and the elongation was 26%, which was superior to the properties of the clad rebar prepared by other process parameters.

12.
Materials (Basel) ; 11(10)2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30326583

RESUMEN

We elucidate here the determining role of Nb interlayer on mechanical properties of Ti/steel clad plate fabricated by vacuum rolling cladding (VRC) as a function of different heating temperatures. A critical analysis on the clad interface via electron probe micro-analyzer, X-ray diffractometer and shear testing were conducted to investigate the influence of TiC, Fe-Nb and TiFe compounds and Nb-Ti solid solution on microstructural evolution and shear properties of Ti/steel clad plate. The inter-diffusion between Ti, C and Fe was effectively restrained by adding the Nb interlayer at heating temperature of 800 °C, and average shear strength of 279 MPa was achieved. With increase of heating temperature, Nb-Ti solid solution was formed at the Ti/Nb interface, which reduced mechanical properties of clad plate at 900 °C. At 1000 °C, TiC and Nb-Fe compounds and Nb-Ti solid solution were formed at the interface, and minimum average shear strength of 152 MPa was achieved. The detailed analysis on the clad interface suggested that ideal shear strength can be obtained through the addition of Nb interlayer and selecting appropriate heating temperature.

13.
Materials (Basel) ; 11(9)2018 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-30134582

RESUMEN

In this study, the impact of different surface treatment and degree of vacuum on the interface and mechanical properties of 304/Q345 stainless steel clad plate was investigated. The study indicated that more continuous or aggregated Al2O3 and Si-Mn composite oxides were formed at the interface after brush grinding. However, less inclusions such as Al2O3, MnS and Ca-Mg-Al-Si composite oxides were formed at the interface after pickling treatment. For the vacuum degrees of 10-2 Pa, 1 Pa and 105 Pa, the oxidation reaction became more intense with the decrease in vacuum degree. The interface inclusions were gradually changed from Al2O3 and Si-Mn complex oxides to oxide scale and MnCr2O4 spinel oxide. The interfacial bonding strength of stainless steel clad plate was improved with the increase in degree of vacuum. The bonding strength was 55 MPa at vacuum of 105 Pa, but it was 484 MPa at vacuum of 10-2 Pa, which is far greater than that of the national standard, and an excellent performance was obtained.

14.
Lupus ; 27(12): 1973-1979, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30041578

RESUMEN

Several susceptibility genes have been associated with systemic lupus erythematosus (SLE) across different populations worldwide. However, data on association between genetic polymorphisms and SLE from Indian population is scarce. We aimed to replicate the association of single nucleotide polymorphisms (SNPs) in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes with susceptibility to SLE in a North Indian population. Three hundred and ninety-four SLE patients and 583 unrelated healthy controls of the same ethnic background were enrolled. All samples were genotyped for SNPs in ITGAM (rs1143679), TNFSF4 (rs2205960), TNFAIP3 (rs5029939) and STAT4 (rs7574865) using TaqMan genotyping assay. At allele level, significant association with susceptibility to SLE was detected with polymorphisms in ITGAM (A vs. G, odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.30-2.30, p < 0.001), TNFSF4 (T vs. G, OR = 1.33, 95% CI = 1.08-1.64, p < 0.01), TNFAIP3 (G vs. C, OR = 1.91, 95% CI = 1.27-2.85, p < 0.01) and STAT4 (T vs. G, OR = 1.38, 95% CI = 1.13-1.69, p < 0.01). All four SNPs were associated with SLE under a dominant model with an OR of 1.47 (95% CI = 1.07-2.04, p < 0.05) for ITGAM, 1.30 (95% CI = 1.01-1.69, p < 0.05) for TNFSF4, 1.90 (95% CI = 1.25-2.90, p < 0.01) for TNFAIP3 and 1.38 (95% CI = 1.06-1.78, p < 0.05) for STAT4. Under a recessive model, significant association was found with ITGAM (OR = 4.87, 95% CI = 2.17-10.91, p < 0.001), TNFSF4 (OR = 1.84, 95% CI = 1.13-3.00, p < 0.05) and STAT4 (OR = 1.82, 95% CI = 1.19-2.77, p < 0.01). In conclusion, single nucleotide polymorphisms in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes are associated with susceptibility to SLE in a North Indian population.


Asunto(s)
Antígeno CD11b/genética , Lupus Eritematoso Sistémico/genética , Ligando OX40/genética , Factor de Transcripción STAT4/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , India , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple
15.
East Asian Arch Psychiatry ; 28(2): 64-67, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29921743

RESUMEN

Arachnoid cysts are benign space-occupying brain lesions that contain cerebrospinal fluid. Most cases are congenital in origin, caused by failed fusion of the arachnoid membrane early in fetal development. Cases are often incidentally detected on neuroimaging; however, rarely patients present with neuropsychiatric manifestations when cysts expand and cause a midline shift, compression of nearby brain tissue or cerebrospinal fluid compartments or both. We report a case of a 56-year-old woman with no past history or family history of psychiatric illness who developed acute-onset right-sided weakness, depressive symptoms, and other neuropsychiatric deficits. A diagnosis of organic mood disorder caused by an arachnoid cyst was made. Her symptoms and neuropsychiatric deficits remitted after cyst marsupialisation by open craniotomy. Therefore, it is important to investigate the organic aetiology in elderly patients who present with simultaneous mood disorder and cognitive dysfunction.


Asunto(s)
Quistes Aracnoideos/psicología , Depresión/etiología , Quistes Aracnoideos/complicaciones , Depresión/complicaciones , Femenino , Humanos , Persona de Mediana Edad
16.
Sci Rep ; 8(1): 7908, 2018 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-29784921

RESUMEN

We describe here the relationship between grain structure, deformation mechanism and fracture characteristics in an austenitic stainless steel. This was accomplished using the novel concept of phase reversion that enabled a wide range of grain size from nanograined/ultrafine grained (NG/UFG) to coarse-grained (CG) regime to be obtained in a single material through change in temperature-time annealing sequence. In the NG/UFG structure, a marked increase in abundance of stacking faults (SFs) and twin density with strain was observed that led to a decrease in the average spacing between adjacent SFs, thus converting stacking faults into twins. Twinning in NG/UFG structure involved partial dislocations and their interaction with the grain boundaries, including SF overlapping and the coordinated nucleation of partial dislocations from the grain boundaries. The plastic zone in the NG/UFG structure resembled a network knitted by the intersecting twins and SFs. With SFE ~30 mJ/m2, the minimum stress for twin nucleation was ~250 MPa for the experiment steel and the corresponding optimal grain size (dop) wa ~120 nm. In contrast, in the CG structure, strain induced martensite formation was the deformation mechanism. The difference in the deformation mechanism led to a clear distinction in the fracture behavior from striated fracture in high strength-high ductility NG/UFG alloy to microvoid coalescence in the low strength-high ductility CG counterpart. The underlying reason for the change in fracture behavior was consistent with change in deformation mechanism from nanoscale twinning in NG/UFG alloy to strain-induced martensite in the CG alloy, which is related to change in the stability of austenite with grain size. An analysis of critical shear stress required to initiate twinning partial dislocations in comparison to that required to nucleate shear bands is presented. The appearance of striated fracture in the NG/UFG alloy suggests a quasi-static step wise crack growth process.

17.
Sci Rep ; 7(1): 2679, 2017 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-28578391

RESUMEN

We describe here innovative processing of low alloy medium-carbon steel with a duplex microstructure composed of nanoscale spheroidized cementite (Fe3C) in an ultrafine-grained (UFG) ferritic steel. After multi-pass rolling and intermittent annealing at 550 °C for 300 s, the obtained UFG-1 steel showed an average ferrite grain size of ~430 nm, containing nanoscale spheroidized cementite (Fe3C) particles with an average size of ~70 nm. On annealing at 600 °C for 300 s, the average size of ferritic grains was increased to ~680 nm and the average size of spheroidized Fe3C particles increased to ~90 nm, referred as UFG-2 steel. Tensile tests indicated that UFG-1 steel had high yield strength (σ y) of 1260 MPa, and ultimate tensile strength (σ UTS) of 1400 MPa. These values are higher than that of UFG-2 steel (σ y = 1080 MPa and σ UTS = 1200 MPa), suggesting that the strengthening contribution is a cumulative effect of decrease in ferrite grain size and nanoscale cementite. The incoherent interfaces between nanosized particles and the matrix acted as a strong barrier to dislocation motion. The study underscores that nanosized precipitates not only provide strength but also contribute to ductility, which is very encouraging for improving the ductility of medium-carbon steels.

18.
Immunol Lett ; 185: 1-11, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28274793

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B-lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment.


Asunto(s)
Linfocitos B/fisiología , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Células TH1/inmunología , Animales , Autoanticuerpos/metabolismo , Proliferación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Humanos , Lipopolisacáridos/inmunología , Activación de Linfocitos/genética , Ratones , Ratones Noqueados , Terapia Molecular Dirigida , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/genética
19.
Clin Exp Immunol ; 187(2): 234-241, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27706807

RESUMEN

Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with juvenile idiopathic arthritis-enthesitis-related arthritis (JIA-ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16 expression, monocytes are classified as classical, intermediate and non-classical. In response to Toll-like receptor (TLR) stimulation, intermediate monocytes produce proinflammatory cytokines and play a role in inflammatory diseases. Therefore, we have studied the microarray profile of monocytes, the frequency of their subsets and cytokine production. Monocyte-specific microarray analysis was performed in six healthy controls' PBMC and six patients' PBMC and SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients with JIA-ERA and 17 healthy controls and 17 disease controls by flow cytometry. Interleukin (IL)-23 and tumour necrosis factor (TNF) levels were measured in culture supernatants of eight controls and seven patients' PBMC/SFMC with/without lipopolysaccharide (LPS) stimulation. Cytokine-producing intermediate monocytes were assessed by flow cytometry. Genes related to antigen presentation, cytokine signalling and TLR pathway were regulated differentially in PB and synovial monocytes of patients with JIA-ERA. Key genes of intermediate monocytes, such as CLEC10A and MARCO, were expressed three- to fourfold more in JIA-ERA. In PB, the frequency of intermediate monocytes was significantly higher in JIA-ERA (4·90% ± 3·5) compared to controls (1·8% ± 1·06; P < 0·001). Patients' synovial cells also had more intermediate monocytes compared to PB (11·25% ± 11·32, 5·9% ± 4·8; P = 0.004). Intermediate monocytes are the major producers of IL-23. Thus, intermediate monocytes may play an important role in JIA-ERA, possibly by producing cytokines, and contribute to joint inflammation.


Asunto(s)
Artritis Juvenil/inmunología , Lectinas Tipo C/genética , Monocitos/fisiología , Receptores Inmunológicos/genética , Membrana Sinovial/inmunología , Adolescente , Adulto , Diferenciación Celular , Células Cultivadas , Niño , Femenino , Humanos , Interleucina-23/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Lipopolisacáridos/inmunología , Masculino , Receptores de IgG/metabolismo , Análisis de Matrices Tisulares , Factor de Necrosis Tumoral alfa/metabolismo , Adulto Joven
20.
Clin Exp Immunol ; 187(3): 376-382, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27804111

RESUMEN

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) help in B cell activation, maintenance and plasma cell survival. B cell infiltration has been demonstrated in kidneys of patients with lupus nephritis (LN). Serum levels of BAFF and APRIL have shown inconsistent relationships with lupus disease activity. We evaluated urinary levels of BAFF and APRIL as biomarker for LN. Thirty-six patients with proliferative lupus nephritis (AN), 10 with active lupus without nephritis (AL) and 15 healthy controls (HC) were studied. APRIL and BAFF levels were measured in both serum and urine using enzyme-linked immunosorbent assay (ELISA). Urine levels were normalized for urinary creatinine excretion. Urine levels were correlated with conventional disease activity markers and histology. Levels were reassessed in 20 AN patients at 6 months after treatment with cyclophosphamide. Urinary APRIL (uAPRIL) and BAFF (uBAFF) levels were raised significantly in AN. uAPRIL, but not uBAFF, correlated moderately with renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in AN (r = 0·36, P < 0·05). On receiver operator curve (ROC) analysis, uBAFF and uAPRIL showed an area under the curve (AUC) of 0·825 and 0·781, respectively, in differentiating between nephritis and non-nephritis, which performed better than low C3, C4 and raised anti-dsDNA antibodies. There was no correlation of serum levels with uBAFF (r = 0·187, P = 0·261) and uAPRIL (r = 0·114, P = 0·494). uAPRIL levels reduced after treatment (mean 125 pg/mg to 36 pg/mg, P < 0·05). uBAFF levels reduced in 16 responders while two of four non-responders had increase in levels. Thus, uBAFF and uAPRIL are potential biomarkers of proliferative lupus nephritis.


Asunto(s)
Factor Activador de Células B/orina , Biomarcadores/orina , Lupus Eritematoso Sistémico/orina , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/orina , Adulto , Linfocitos B/efectos de los fármacos , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/orina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
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