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1.
J Orthop Trauma ; 38(2): 57-64, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38031262

RESUMO

OBJECTIVES: To compare clinical and radiographic outcomes after retrograde intramedullary nailing (rIMN) versus locked plating (LP) of "extreme distal" periprosthetic femur fractures, defined as those that contact or extend distal to the anterior flange. DESIGN: Retrospective review. SETTING: Eight academic level I trauma centers. PATIENT SELECTION CRITERIA: Adult patients with periprosthetic distal femur fractures at or distal to the anterior flange (OTA/AO 33B-C[VB1]) treated with rIMN or LP. OUTCOME MEASURES AND COMPARISONS: The primary outcome was reoperation to promote healing or to treat infection (reoperation for elective removal of symptomatic hardware was excluded from this analysis). Secondary outcomes included nonunion, delayed union, fixation failure, infection, overall reoperation rate, distal femoral alignment, and ambulatory status at final follow-up. Outcomes were compared between patients treated with rIMN or LP. RESULTS: Seventy-one patients treated with rIMN and 224 patients treated with LP were included. The rIMN group had fewer points of fixation in the distal segment (rIMN: 3.5 ± 1.1 vs. LP: 6.0 ± 1.1, P < 0.001) and more patients who were allowed to weight-bear as tolerated immediately postoperatively (rIMN: 45%; LP: 9%, P < 0.01). Reoperation to promote union and/or treat infection was 8% in the rIMN group and 16% in the LP group ( P = 0.122). There were no significant differences in nonunion ( P > 0.999), delayed union ( P = 0.079), fixation failure ( P > 0.999), infection ( P = 0.084), or overall reoperation rate ( P > 0.999). Significantly more patients in the rIMN group were ambulatory without assistive devices at final follow-up (rIMN: 35%, LP: 18%, P = 0.008). CONCLUSIONS: rIMN of extreme distal periprosthetic femur fractures has similar complication rates compared with LP, with a possible advantage of earlier return to weight-bearing. Surgeons can consider this treatment strategy in all fractures with stable implants and amenable prosthesis geometry, even extreme distal fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas Periprotéticas , Adulto , Humanos , Fixação Intramedular de Fraturas/efeitos adversos , Estudos Retrospectivos , Fraturas do Fêmur/etiologia , Consolidação da Fratura , Placas Ósseas/efeitos adversos , Fixação Interna de Fraturas , Fêmur/cirurgia , Fraturas Periprotéticas/complicações , Artroplastia do Joelho/efeitos adversos , Resultado do Tratamento
2.
Cartilage ; : 19476035231214724, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38018451

RESUMO

OBJECTIVE: The use of porcine animal models for cartilage injury has increased recently due to their similarity with humans with regard to cartilage thickness, limited intrinsic healing of chondral defects, and joint loading biomechanics. However, variations in the mechanical and biochemical properties of porcine hip articular cartilage among various tissue ages and weightbearing (WB) regions are still unknown. This study's aim was to characterize the mechanical and biochemical properties of porcine hip articular cartilage across various ages and WB regions. METHODS: Articular cartilage explants were harvested from WB and non-weightbearing (NWB) surfaces of the femoral head and acetabulum of domesticated pigs (Sus scrofa domesticus) at fetal (gestational age: 80 days), juvenile (6 months), and adult (2 years) ages. Explants underwent compressive stress-relaxation mechanical testing, biochemical analysis for total collagen and glycosaminoglycan (GAG) content, and histological staining. RESULTS: Juvenile animals consistently had the highest mechanical properties, with 2.2- to 7.6-time increases in relaxation modulus, 1.3- to 2.3-time increases in instantaneous modulus, and 4.1- to 14.2-time increases in viscosity compared with fetal cartilage. Mechanical properties did not significantly differ between the WB and NWB regions. Collagen content was highest in the NWB regions of the juvenile acetabulum (65.3%/dry weight [DW]) and femoral head (75.4%/DW) cartilages. GAG content was highest in the WB region of the juvenile acetabulum (23.7%/DW) and the WB region of the fetal femoral head (27.5%/DW) cartilages. Histological staining for GAG and total collagen content followed the trends from the quantitative biochemical assays. CONCLUSION: This study provides a benchmark for the development and validation of preclinical porcine models for hip cartilage pathologies.

3.
Cartilage ; : 19476035231163273, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36974340

RESUMO

OBJECTIVE: Fibrin sealants are routinely used for intra-articular surgical fixation of cartilage fragments and implants. However, the mechanical properties of fibrin sealants in the context of cartilage repair are unknown. The purpose of this study was to characterize the adhesive and frictional properties of fibrin sealants using an ex vivo model. DESIGN: Native bovine cartilage-bone composites were assembled with a single application of Tisseel or Vistaseal. Composites were tested in tension and lap shear. In addition, the coefficient of friction (COF) was measured in a native cartilage annulus model alone and with minced cartilage. Finally, the effect of a double application of fibrin sealant was evaluated. RESULTS: There were no significant differences in tensile modulus, ultimate tensile strength (UTS), shear modulus, or ultimate shear strength (USS) between the 2 fibrin sealants. Both fibrin sealants demonstrated a UTS and USS of <8 and <30 kPa, respectively. There were no differences in COF between the sealants when tested alone or with minced cartilage. A double application of fibrin sealant did not alter the mechanical properties compared with a single application of fibrin sealant. CONCLUSIONS: Fibrin sealant adhesive properties are not affected by the sealant type studied or the number of applications in a bovine cartilage-bone model. Fibrin sealant tribological properties are not affected by sealant type or the addition of minced cartilage. The adhesive properties of Tisseel and Vistaseal were less than those desired for the in vivo fixation of cartilage repair implants. These findings motivate the development of an improved cartilage-specific adhesive for cartilage repair applications.

4.
Arthroplast Today ; 19: 101093, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36691463

RESUMO

Background: Periprosthetic fractures are a devastating complication of total hip arthroplasty (THA) and are associated with significantly higher mortality rates in the postoperative period. Given the strain that periprosthetic fractures place on the patient as well as the healthcare system, identifying and optimizing medical comorbidities is essential in reducing complications and improving outcomes. Methods: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program database. Demographic data, preoperative laboratory values, medical comorbidities, hospital course, and acute complications were collected and compared between patients with and without readmission for a periprosthetic fracture. A multivariate logistic regression analysis was performed to determine associated independent risk factors for periprosthetic fractures after index THA. Results: The analysis included 275,107 patients, of which 2539 patients were readmitted for periprosthetic fractures. Patients with postoperative fractures were more likely to be older (>65 years), females, BMI >40, and increased medical comorbidities. Preoperative hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rates were independent risk factors for sustaining a periprosthetic fracture and readmission within 30 days. Modifiable patient-related factors of concurrent smoking and chronic steroid use at the time of index THA were also independent risk factors for periprosthetic fractures. Inpatient metrics of longer length of stay, operative time, and discharge to rehab predicted postarthroplasty fracture risk. Readmitted fracture patients subsequently had increased risks of developing a surgical site infection, urinary tract infection, and requiring blood transfusions. Conclusions: Patients with hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rate are at increased risk for sustaining periprosthetic fractures after THA. Preoperative optimization with close monitoring of metabolic markers and modifiable risk factors may help not only prevent acute periprosthetic fractures but also associated infection and bleeding risk with fracture readmission.

5.
Orthop Surg ; 15(2): 432-439, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36444954

RESUMO

OBJECTIVE: Previous studies have sought to determine the effects of total knee arthroplasty (TKA) using kinematic alignment (KA) versus mechanical alignment (MA) to reproduce the native knee alignment and soft tissue envelope for improved patient satisfaction. There are limited studies that compare acute perioperative outcomes between KA and MA patients as it pertains to pain-related opioid consumption and hospital length of stay (LOS). This study aims to compare early KA and MA in restoring function and rehabilitation after surgery to reduce hospitalization and opioid consumption. METHODS: A retrospective review of 42 KA and 58 MA primary TKA patients performed by a single surgeon between 2020-2021 was conducted. Demographics were controlled between groups and radiographic measurements and functional outcomes were compared. Pain was evaluated with inpatient/outpatient morphine milligram equivalents (MME) and visual analogue scale (VAS) scores. Mobility was assessed using multiple measures by a physical therapist. Mean preoperative and 3-month postoperative flexion range of motion (ROM) were analyzed, and overall complications, LOS, and non-home discharge between groups compared. Continuous variables were compared using the Wilcoxon rank-sum test, and categorical variables were compared using the chi-square or Fisher exact test. Statistical significance was set at P < 0.05. RESULTS: KA patients had shorter LOS (1.8 vs 3.1 days) and less cumulative opioid requirements compared to MA patients (578 vs 1253 MME). On postoperative day 0, KA patients ambulated on average twice the distance of MA patients (20 vs 6.5 feet). KA patients had residual tibia component in varus (1.4° vs -0.3°), femoral component in valgus (-1.9° vs 0.2°), and valgus joint line obliquity compared with MA (-1.5° vs 0.2°). There were no significant differences between 3-month postoperative flexion arc motion, discharge destination, KOOS or SF-12 outcomes, and surgical complication rates between groups. CONCLUSIONS: By restoring the native joint line obliquity and minimizing the frequency of ligament releases, KA for TKA may improve pain relief, early mobility, and decreased length of stay compared with traditional methods of establishing neutral limb axis by MA.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Analgésicos Opioides/uso terapêutico , Fenômenos Biomecânicos , Tempo de Internação , Osteoartrite do Joelho/cirurgia , Articulação do Joelho/cirurgia , Amplitude de Movimento Articular
6.
Orthop J Sports Med ; 10(11): 23259671221131303, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36479464

RESUMO

Background: Posterolateral corner (PLC) reconstruction of the knee involves precise drilling of a single tunnel from anterolateral to posteromedial in the fibular head (FH) to ensure adequate graft fixation. Misplacement of the tunnel in a too lateral or too superior trajectory can lead to cortical breach and inadequate graft fixation. Purpose: To (1) determine the mechanical consequence of a lateralized FH tunnel in PLC reconstruction and (2) compare the mechanical strength of 3 salvage fixation techniques for a lateralized FH tunnel. Study Design: Controlled laboratory study. Methods: Sawbones models of a uniform density were utilized. FH tunnels (7-mm diameter) were drilled from anterolateral to posteromedial in positive controls (lateral cortex thickness, 7.6 ± 0.7 mm) to represent an improperly placed FH tunnel at risk of lateral cortical breach. For negative controls and salvage experimental groups, FH tunnels were drilled from anterolateral to posterolateral (lateral cortex thickness, 2.7 ± 0.9 mm). Three salvage fixation techniques were compared: suture anchor fixation, tunnel redrilling, and nitinol staple fixation. Samples (n = 5 per group) underwent uniaxial tension testing, and the ultimate tensile strength (UTS) and mode of failure were recorded. Data were analyzed using the 1-sample t test and nonparametric 1-sample Wilcoxon signed-rank test. Results: The negative control group had a 4-fold lower mean UTS relative to the positive control group (1.49 ± 0.17 vs 6.25 ± 1.98 MPa; P < .01) and exhibited failure through the lateral cortex and tunnel. Nitinol staple fixation improved the mean UTS by >16 times compared with the negative control group (24.06 ± 6.49 vs 1.49 ± 0.17 MPa; P < .01). Suture anchors and tunnel redrilling exhibited similar UTS and mode of failure to those of negative controls. Conclusion: Reinforcement of a thinned lateral FH cortex with a single nitinol staple improved graft fixation strength in a sawbones model. Clinical Relevance: A lateralized FH tunnel can be a common intraoperative pitfall during PLC reconstruction. Salvage of a thinned lateral FH cortex with a single nitinol staple may reduce the risk of cortical breach and graft failure.

7.
Orthop J Sports Med ; 10(9): 23259671221124911, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36186712

RESUMO

Background: Postoperative knee arthrofibrosis is a common and potentially detrimental complication affecting knee function and gait. Several cohort studies have reported good outcomes after arthroscopic lysis of adhesions (LOA) with manipulation under anesthesia (MUA). Purpose: To review the literature assessing the efficacy and complications of arthroscopic LOA and MUA for postoperative arthrofibrosis of the knee and evaluate whether any relevant subgroups are associated with different clinical presentation and outcomes. Study Design: Systematic review; Level of evidence, 4. Methods: This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible studies published from January 1, 1990, to April 1, 2021, were identified through a search of the US National Library of Medicine (PubMed/MEDLINE), EMBASE, and Cochrane databases. All studies included in this analysis included pre- and postoperative range of motion measurements for their treated patients. Studies reporting outcomes for patients with isolated cyclops lesions after anterior cruciate ligament reconstruction were excluded. Results: Eight studies comprising 240 patients were included. The mean time from index surgery to arthroscopic LOA and MUA was 8.4 months, and the mean postoperative follow-up was at 31.2 months. All studies demonstrated a significant improvement (41.6°) in arc of motion after arthroscopic LOA. Clinically significant improvements in outcome measures, including the International Knee Documentation Committee, Western Ontario and McMaster Universities Osteoarthritis Index, and Knee injury and Osteoarthritis Outcome Score, were reported after arthroscopic LOA across all applicable studies. Of 240 patients, a single complication (synovial fistula) occurred after LOA and MUA, which resolved without intervention. Conclusion: The results of this review indicated that arthroscopic LOA and MUA is a safe and efficacious treatment for postoperative arthrofibrosis of the knee.

8.
Life (Basel) ; 12(9)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36143381

RESUMO

Although long term pain and mobility outcomes in total knee arthroplasties (TKA) are successful, many patients experience significant amount of debilitating pain during the immediate post-operative period that necessitates narcotic use. Percutaneous cryoneurolysis to the infrapatellar saphenous and anterior femoral cutaneous nerves may help to better restore function and rehabilitation after surgery while limiting narcotic consumption. A retrospective chart review of primary TKA patients receiving pre-operative cryoneurolysis from 2019 to 2020 was performed to assess total opioid morphine milligram equivalents (MME) consumed inpatient and at interval follow-up. Demographics and medical comorbidities were compared between cryoneurolysis and age-matched control patients to assess baseline characteristics. Functional rehabilitation outcomes, including knee range of motion (ROM), ambulation distance, and Boston AM-PAC scores, as well as patient reported outcomes using the KOOS JR and SF-12 scores were analyzed using STATA 17 Software. The analysis included 29 cryoneurolysis and 28 age-matched control TKA patients. Baseline demographics and operative technique were not significant between groups. Although not statistically significant, cryoneurolysis patients had a shorter length of stay (2.5 vs. 3.5 days) and overall less inpatient and outpatient MME requirements. Cryoneurolysis patients had statistically significant improved 6-week ROM and 1-year follow-up KOOS JR and SF-12 mental scores compared to the control. There were no differences in complication rates. Cryoneurolysis is a safe, effective treatment modality to improve active functional recovery and patient satisfaction after TKA by reducing MME requirements. Patients who underwent cryoneurolysis had on average fewer MME prescribed during the perioperative period, improved active ROM, and improved patient-reported outcomes with no associated increased risk of infections, deep vein thrombosis, or neurologic complications.

9.
Arthrosc Tech ; 11(4): e675-e679, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35493055

RESUMO

Recognition and treatment of injuries to the posterolateral (PLC) corner of the knee have increased in recent decades. Despite advancements in surgical technique, complications can occur in up to 20% of PLC reconstructions. Lateralization of the fibular tunnel during drilling is a common intraoperative pitfall and can lead to cortical breach or fibular head fracture after graft tensioning. Compression staples have been increasingly used for fracture fixation in the hand, foot, and ankle. Because of its pseudo-elastic properties, insertion of a low-profile, compressive Nitinol staple could serve as an intraoperative salvage technique to reinforce and prevent failure through a thin lateral cortex of the fibular head. The purpose of this Technical Note is to describe a reproducible technique for the implementation of a Nitinol staple for reinforcement of a lateralized fibular tunnel in posterolateral corner reconstruction.

10.
Orthop J Sports Med ; 10(5): 23259671221093391, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35571970

RESUMO

Background: Comparative studies and randomized controlled trials (RCTs) often use the P (probability) value to convey the statistical significance of their findings. P values are an imperfect measure, however, and are vulnerable to a small number of outcome reversals to alter statistical significance. The inclusion of a fragility index (FI) and fragility quotient (FQ) may aid in the interpretation of a study's statistical strength. Purpose/Hypothesis: The purpose of this study was to examine the statistical stability of studies comparing single-row to double-row rotator cuff repair. It was hypothesized that the findings of these studies would be vulnerable to a small number of outcome event reversals, often fewer than the number of patients lost to follow-up. Study Design: Systematic review; Level of evidence, 3. Methods: We analyzed comparative studies and RCTs on primary single-row versus double-row rotator cuff repair that were published between 2000 and 2021 in 10 leading orthopaedic journals. Statistical significance was defined as a P < .05. The FI for each outcome was determined by the number of event reversals necessary to alter significance. The FQ was calculated by dividing the FI by the respective sample size. Results: Of 4896 studies screened, 22 comparative studies, 10 of which were RCTs, were ultimately included for analysis. A total of 74 outcomes were examined. Overall, the median FI was 2 (interquartile range [IQR], 1-3), and the median FQ was 0.035 (IQR, 0.020-0.057). The mean FI was 2.55 ± 1.29, and the mean FQ was 0.043 ± 0.027. In 64% of outcomes, the FI was less than the number of patients lost to follow-up.) Additionally, 81% of significant outcomes needed just a single outcome reversal to lose their significance. Conclusion: Over half of the studies currently used to guide clinical practice have a number of patients lost to follow-up greater than their FI. The results of these studies should be interpreted within the context of these limitations. Future analyses may benefit from the inclusion of the FI and the FQ in their statistical analyses.

11.
Int J Sports Phys Ther ; 16(3): 941-958, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34123544

RESUMO

For the treatment of large chondral and osteochondral defects of the knee, osteochondral allograft transplantation (OCA) is an effective solution with relatively high rates of return to sport. In professional athletes, rehabilitation following OCA is a critical component of the process of returning the athlete to full sports activity and requires a multidisciplinary team approach with frequent communication between the surgical and rehabilitation teams (physical therapists, athletic trainers, coaching staff). In this review, we describe our five-phase approach to progressive rehabilitation of the professional athlete after OCA, which takes into account the biological processes of healing and optimization of neuromuscular function required for the demands of elite-level sport. The principles of early range of motion, proper progression through the kinetic chain, avoidance of pain and effusion, optimization of movement, regimen individuation, and integration of sports-specific activities underlie proper recovery.

12.
Am Surg ; 86(10): 1264-1268, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33076680

RESUMO

Diabetes mellitus (DM) and hypertension (HTN) are increasing in prevalence in the population. Level 1 trauma facilities are often faced with managing these chronic conditions. Recent studies indicated that 12-44% of patients presenting traumas are found to have incidental findings by imaging representing undiagnosed medical conditions, with 10% reported requiring further management [Surendran A, Mori A, Varma DK, Gruen RL. Systematic review of the benefits and harms of whole-body computed tomography in the early management of multitrauma patients: Are we getting the whole picture? J Trauma and Acute Care Surg. 2014;76(4):1122-1130]. Between 2015 and 2016, 852 patients seen at a level 1 trauma center were analyzed. Patients were evaluated who received a new diagnosis of HTN or DM, or had preexisting diagnosis of HTN or DM whose management was changed. Uncontrolled HTN or DM was defined as a need for either a change in medication or primary care optimization prior to discharge. Among the patients evaluated, 6.3% and 3.0% received new diagnoses of HTN and DM, respectively. Additionally, 34.4% and 35.3% of patients were found to have uncontrolled HTN and DM and required medical optimization, respectively. The high prevalence of undiagnosed or suboptimal management for chronic conditions indicates that more research is warranted for defining, screening for, and treating surgical patients with poorly controlled medical conditions with these comorbidities.


Assuntos
Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Centros de Traumatologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Demografia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Achados Incidentais , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Neurotherapeutics ; 17(2): 539-562, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367476

RESUMO

Cardiac arrest (CA) afflicts ~ 550,000 people each year in the USA. A small fraction of CA sufferers survive with a majority of these survivors emerging in a comatose state. Many CA survivors suffer devastating global brain injury with some remaining indefinitely in a comatose state. The pathogenesis of global brain injury secondary to CA is complex. Mechanisms of CA-induced brain injury include ischemia, hypoxia, cytotoxicity, inflammation, and ultimately, irreversible neuronal damage. Due to this complexity, it is critical for clinicians to have access as early as possible to quantitative metrics for diagnosing injury severity, accurately predicting outcome, and informing patient care. Current recommendations involve using multiple modalities including clinical exam, electrophysiology, brain imaging, and molecular biomarkers. This multi-faceted approach is designed to improve prognostication to avoid "self-fulfilling" prophecy and early withdrawal of life-sustaining treatments. Incorporation of emerging dynamic monitoring tools such as diffuse optical technologies may provide improved diagnosis and early prognostication to better inform treatment. Currently, targeted temperature management (TTM) is the leading treatment, with the number of patients needed to treat being ~ 6 in order to improve outcome for one patient. Future avenues of treatment, which may potentially be combined with TTM, include pharmacotherapy, perfusion/oxygenation targets, and pre/postconditioning. In this review, we provide a bench to bedside approach to delineate the pathophysiology, prognostication methods, current targeted therapies, and future directions of research surrounding hypoxic-ischemic brain injury (HIBI) secondary to CA.


Assuntos
Parada Cardíaca/complicações , Hipóxia-Isquemia Encefálica , Animais , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia
14.
J Am Chem Soc ; 139(23): 7872-7885, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28528544

RESUMO

O-GlcNAc modification (O-GlcNAcylation) is required for survival in mammalian cells. Genetic and biochemical experiments have found that increased modification inhibits apoptosis in tissues and cell culture and that lowering O-GlcNAcylation induces cell death. However, the molecular mechanisms by which O-GlcNAcylation might inhibit apoptosis are still being elucidated. Here, we first synthesize a new metabolic chemical reporter, 6-Alkynyl-6-deoxy-GlcNAc (6AlkGlcNAc), for the identification of O-GlcNAc-modified proteins. Subsequent characterization of 6AlkGlcNAc shows that this probe is selectively incorporated into O-GlcNAcylated proteins over cell-surface glycoproteins. Using this probe, we discover that the apoptotic caspases are O-GlcNAcylated, which we confirmed using other techniques, raising the possibility that the modification affects their biochemistry. We then demonstrate that changes in the global levels of O-GlcNAcylation result in a converse change in the kinetics of caspase-8 activation during apoptosis. Finally, we show that caspase-8 is modified at residues that can block its cleavage/activation. Our results provide the first evidence that the caspases may be directly affected by O-GlcNAcylation as a potential antiapoptotic mechanism.


Assuntos
Acetilglucosamina/metabolismo , Apoptose , Caspases/metabolismo , Acetilglucosamina/química , Animais , Caspases/química , Glicosilação , Humanos , Cinética , Células MCF-7 , Camundongos , Células NIH 3T3
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