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1.
J Hand Surg Am ; 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516939

RESUMO

PURPOSE: Thumb carpometacarpal (CMC) osteoarthritis (OA) causes functional disability and an increased health care burden in the aging population. The role of therapy in thumb CMC OA has been minimally analyzed in the literature. We hypothesized that patients treated with therapy for thumb CMC OA would demonstrate reduced rates of surgery for this diagnosis. METHODS: We queried a national insurance dataset for all patients with an International Classification of Diseases, Ninth Revision, or International Statistical Classification of Diseases, Tenth Revision, code for thumb CMC OA, with a minimum of 2 years of follow-up. A 2:1 propensity-matched cohort of patients with CMC OA who did not receive therapy versus a therapy cohort was created, with a minimum of two sessions of hand therapy for inclusion. The primary outcome was the rate of thumb CMC OA surgery occurring within 2 years of diagnosis; time to surgery and use of thumb CMC injections were secondary outcomes. Multivariable logistic regression analysis was used to identify the risk factors for undergoing surgical treatment. RESULTS: After matching, the therapy cohort comprised 14,548 patients, with a matched group of 28,930 patients who did not undergo therapy. In the overall sample, the rate of surgery within 2 years was 22.5%. Two-year surgical treatment rates were significantly higher for those who did not undergo therapy when compared with those who did (29.3% vs 13.1%). Patients treated with therapy had a significantly longer time to surgery, with no difference in the rate of surgery after one year. In multivariable regression of all included variables, lack of therapy intervention had the highest odds of surgery for thumb CMC OA (odds ratio 4.3). CONCLUSIONS: We present the findings of a large insurance database evaluating the association of therapy with rates of surgical treatment for thumb CMC arthritis. On average, those treated with therapy had longer times to surgery, and the 2-year surgery rates for patients diagnosed with thumb CMC arthritis were significantly higher in those who did not undergo therapy treatment. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

2.
JBJS Rev ; 11(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722822

RESUMO

¼: Gun violence-related and firearm-related injuries are a public health crisis with increasing rates, particularly among younger demographics, in the United States despite a decline in incidence worldwide. ¼: There exists limited high-quality evidence to guide the management of firearm-related orthopaedic injuries. ¼: Associated injuries (i.e., neurological and vascular) are common in ballistic injuries to the extremity. ¼: Where indicated, low-energy orthopaedic injuries can be managed successfully with standard fixation and management strategies with similar complications to closed fractures.

3.
Eur J Orthop Surg Traumatol ; 33(4): 1091-1099, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35380277

RESUMO

PURPOSE: Ballistic fractures of the femoral condyles are rare injuries with limited literature to help guide treatment. The purpose of this study is to report on the presentation, management, and outcomes for patients with isolated ballistic condylar fractures. METHODS: Eighteen patients between ages 16 and 65 with low-energy ballistic injuries isolated to the femoral condyles (OTA 33B) were included, 15 with CT imaging. Clinical records and imaging were reviewed, as well as treatment strategy. Fractures were classified by AO/OTA classification. Outcome and follow-up data were gathered at outpatient appointments and telephone calls. RESULTS: Of the 18 patients, 78% were treated operatively (61% with open reduction and internal fixation, 17% with removal of foreign body alone). There were two instances of traumatic vascular injury and no neurologic injuries. Furthermore, there were no identified infections. Only 58% of the patients had follow-up for more than 6 weeks with average KOOS Jr. Score of 50, and average VAS pain score of 5.2. CONCLUSIONS: Ballistic femoral condyle fractures are rare Orthopaedic injuries seen in relatively high frequency at our institution. Most (78%) were treated operatively and with few complications. These fractures are not easily classified according to common classification schemes and may benefit from more rigorous study to guide treatment and anticipate outcomes.


Assuntos
Fraturas do Fêmur , Fraturas do Colo Femoral , Fraturas do Joelho , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Fêmur , Fraturas do Fêmur/cirurgia , Resultado do Tratamento
4.
Eur J Orthop Surg Traumatol ; 33(2): 409-414, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35038011

RESUMO

OBJECTIVE: The purpose of this study is to determine the rate of femoral neck fractures in patients who have sustained bilateral femur fractures compared to unilateral femur fractures. DESIGN AND SETTING: A retrospective review of an institutional trauma database was completed at a single level 1 trauma academic medical center. PATIENTS: All patients treated for a femur fracture between May 1, 2018 and December 31, 2020 were included. RESULTS: Twenty-one patients sustained bilateral femur fractures (11%) and 166 sustained unilateral femur fractures. Fifteen associated ipsilateral femoral neck fractures were identified. Eight of the 15 (53%) associated femoral neck fractures were observed in patients who sustained bilateral femur fractures. Eight of the 21 patients with bilateral femur fractures, 42 fractures in total, had an associated ipsilateral femoral neck fracture (38% of patients; 19% of fractures, respectively), while only seven of the 166 patients (4%) with a unilateral femur fracture had an associated femoral neck fracture (p < 0.001). Of the 208 femur fractures, 19 (9%) were open fractures. Ten of the 21 patients with bilateral femur fractures, 42 fractures in total, were identified to have an open femur fracture (48% of patients, 24% of fractures), while only nine of the 166 (5%) unilateral femur fractures were open (p < 0.001). CONCLUSIONS: Our results demonstrate an association between bilateral femur fractures, open femur fractures, and associated femoral neck fractures. Surgeons treating these injuries should maintain a high index of suspicion for associated ipsilateral proximal.


Assuntos
Fraturas do Fêmur , Fraturas do Colo Femoral , Fraturas Expostas , Traumatismo Múltiplo , Humanos , Fraturas do Colo Femoral/complicações , Fraturas do Colo Femoral/cirurgia , Fraturas do Fêmur/complicações , Fraturas do Fêmur/diagnóstico por imagem , Traumatismo Múltiplo/cirurgia , Fraturas Expostas/cirurgia , Fêmur , Estudos Retrospectivos , Colo do Fêmur
5.
Arthrosc Sports Med Rehabil ; 4(4): e1489-e1495, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36033167

RESUMO

Objective: To investigate the effect of multiple concussions on the risk of lower-extremity injuries in National Football League (NFL) players. Methods: All active NFL players from September 2016 to January 2017 through September 2019 to January 2020 regular seasons were eligible for inclusion. All players who sustained multiple concussions during the study period were identified using publicly available data and included in the multiple concussion (MC) cohort. Players who sustained a single concussion (SC) as well as controls were age and position matched to the MC cohort using MEDCALC case-control. Lower-extremity injuries were then documented for the players included in all 3 cohorts. Results: The odds of sustaining a lower-extremity injury were significantly greater in the MC as well as the SC cohort when compared with the no concussion (NC)-matched cohort (odds ratio 2.92, standard deviation [SD] 1.7-4.9) and 2.28 (SD 1.5-3.6), respectively. However, we found no significant difference in the odds of sustaining a lower-extremity injury when comparing the SC with the MC cohort (odds ratio 1.00, SD 0.7-1.3). The time to lower-extremity injury after return to play from a concussion was significantly shorter in the SC group when compared with the MC group, within 1 year following a concussion injury (P = .01). Conclusions: There was a significant increase in the odds of suffering a lower-extremity injury after return to play in NFL players exposed to SC or MC when compared with age- and position-matched controls who did not sustain a concussion within the study period. There was no significant difference in the odds of suffering a lower-extremity injury after return to play for NFL players exposed to MC when compared with players exposed to a SC during our study period. Our findings suggest a potential need for injury-prevention protocols following concussion injuries. Level of Evidence: Level III, retrospective comparative prognostic trial.

6.
J Am Acad Orthop Surg ; 30(3): e384-e394, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35772091

RESUMO

OBJECTIVE: The purpose of this meta-analysis was to determine whether perioperative fascia iliaca compartment blockade (FICB) decreases mortality in patients with hip fracture. METHODS: MEDLINE (PubMed and Ovid platforms), Web of Science, EMBASE, and Cochrane Database of Systemic Reviews were screened for "fascia iliaca compartment block, hip fracture" articles in English, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, from January 1, 2005, to March 1, 2020. All relevant randomized controlled trials and cohort and case-control studies were included for analysis. Relevant article titles were identified, and their corresponding abstracts were independently reviewed by two authors for inclusion. The full-text articles were then obtained for all relevant identified abstracts and assessed for inclusion in the meta-analysis. Conflicts in quality assessment between the two independent reviewers were resolved by a consensus vote of all authors. RESULTS: Study quality was assessed objectively using the Jadad and Newcastle-Ottawa Scale. This meta-analysis was done in accordance with the PRISMA (http://links.lww.com/JAAOS/A731) and QUORUM guidelines. Quantitative synthesis analysis was done using Cochrane Reviews Review Manager (version 5.3). All analyses were completed using random-effects models and comparing the individual effect sizes within each study. DISCUSSION: Management of hip fracture pain with FICB does not markedly decrease short-term mortality. Our findings support the continued use of FICB for the management of hip fractures in geriatric patients and suggest the need for future prospective randomized controlled trials to further determine FICB's effect on short-term and long-term mortality and functional status. LEVEL OF EVIDENCE: Therapeutic level I.


Assuntos
Fraturas do Quadril , Bloqueio Nervoso , Idoso , Fáscia , Fraturas do Quadril/cirurgia , Humanos , Manejo da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Orthop J Sports Med ; 10(3): 23259671211065756, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35284587

RESUMO

Background: Approximately 25% of Major League Baseball (MLB) pitchers undergo medial ulnar collateral ligament reconstruction (UCLR) during their careers. Purpose: To identify risk factors for UCLR that are specific to 2 subgroups of MLB pitchers: right (RHPs)- versus left-handed pitchers (LHPs) and starting (SPs) versus relief pitchers (RPs). Study Design: Case-control study; Level of evidence, 3. Methods: We included 109 MLB pitchers who had undergone UCLR between 2007 and 2019 and had sufficient preinjury data in the 3 years before surgery (T3, T2, T1). A 2:1 matched control cohort was selected for comparison. Pitch velocity, release location, and ball movement were compared between the UCLR and control cohorts in both subgroups in the years before surgery (RHPs vs LHPs and SPs vs RPs). Binary logistic regression was used to identify independent risk factors for UCLR. Results: The mean horizontal release location for the UCLR group was 5.8 cm more lateral than for the control group (P = .028). For all pitchers, every 2.5-cm lateral shift in release location in the years leading up to UCLR equated to a 3.7% increase in the odds of UCLR. For RPs, this risk was more substantial: a 5.8% increase in odds per 2.5 cm. SPs in the UCLR group demonstrated significantly different T1 horizontal release locations compared with SPs in the control group, though not to a statistically significant change over the 3 years before surgery. However, in the 3 years before surgery, the horizontal release location for RPs in the UCLR group moved 2.1 cm more lateral, as compared with 2.7 cm more medial for RPs in the control group (P = .007). For LHPs, a decrease in mean pitch velocity by 1 mph (1.6 km/h) in the years leading up to surgery increased the odds of UCLR by 45%. Conclusion: Increasing lateralization of release point in the years before surgery increased the risk of UCLR, specifically for relievers. Our findings add to the growing body of evidence that release location is an important variable in analyzing the risk of UCLR in MLB and that risk stratification may be dependent on pitcher characteristics such as position, handedness, and weight.

8.
JBJS Case Connect ; 11(2): e20.00805, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34038391

RESUMO

CASE: A 51-year-old woman underwent stage I of a 2-stage revision for a prosthetic knee infection with a vancomycin-impregnated articulating cement spacer followed by IV vancomycin and ceftriaxone. Four weeks later, she developed fevers, a diffuse cutaneous eruption, lymphadenopathy, transaminitis, and acute renal tubular necrosis before being diagnosed with drug reaction with eosinophilia and systemic syndrome (DRESS). CONCLUSION: DRESS is a rare, potentially life-threatening adverse drug reaction with cutaneous manifestations and multiorgan involvement. Although rare, its incidence in orthopaedic patients is likely to increase with the aging population. It must be recognized early to minimize end-stage organ dysfunction and mortality.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eosinofilia , Idoso , Artroplastia/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Eosinofilia/induzido quimicamente , Feminino , Humanos , Articulação do Joelho , Pessoa de Meia-Idade , Vancomicina/efeitos adversos
9.
J Orthop Trauma ; 35(7): 361-365, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33177432

RESUMO

OBJECTIVES: To compare the relative frequencies of intra-articular extension of supracondylar distal femur fractures in blunt versus ballistic trauma and the diagnostic accuracy of conventional radiography in identifying intra-articular extension in these fractures. DESIGN: A retrospective review. SETTING: Urban academic trauma center. STUDY GROUP: Thirty-eight patients were included for analysis, with 19 blunt and 19 ballistic mechanism distal femur fractures. INTERVENTION: Fleiss' kappa score was calculated in determining interobserver reliability of the OTA/AO classification. Radiographic specificity and sensitivity were compared using Fischer exact testing. Quantitative data were compared using 2-tailed t-testing for continuous variables and chi-square tests for proportions. MAIN OUTCOME MEASUREMENTS: Rate of intra-articular extension of ballistic versus blunt supracondylar femur fractures. RESULTS: Seventeen of 19 patients (89.5%) with blunt trauma had intra-articular involvement compared with 5 of 19 patients (26.3%) with ballistic trauma (P = 0.001). For blunt fractures, preoperative radiographs were 94% sensitive for the detection of intra-articular extension compared with 100% sensitive for ballistic fractures (P = 1.000). We identified one case, in the blunt cohort, where the operative plan changed from intramedullary nail to open reduction and internal fixation as a result of the additional coronal plane fracture pattern identified on CT. There were no such occurrences in the ballistic cohort. CONCLUSIONS: The rate of intra-articular extension for ballistic supracondylar femur fractures is lower than blunt distal femur fracture. There were low rates of missed intra-articular fractures and changes in operative plans after reviewing CT imaging for both blunt and ballistic distal femur fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas do Fêmur , Fraturas Intra-Articulares , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/cirurgia , Fêmur , Fixação Interna de Fraturas , Humanos , Fraturas Intra-Articulares/diagnóstico por imagem , Fraturas Intra-Articulares/cirurgia , Reprodutibilidade dos Testes , Estudos Retrospectivos
10.
J Pediatr Orthop ; 40(6): e487-e497, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32501921

RESUMO

BACKGROUND: Osteosarcoma and other primary bone malignancies are relatively common in skeletally immature patients. Current literature features case series with disparate complication rates, making it difficult for surgeons to educate patients on outcomes after limb salvage with expandable prostheses. This study aims to provide an update on complication rates, mortality, and functional outcomes in patients who undergo limb salvage with expandable prostheses for primary bone malignancies. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An exhaustive PubMed/Medline and Cochrane search of peer-reviewed published literature from 1997 to 2017 was performed, yielding a total of 1350 studies. After multiple rounds of review for inclusion and exclusion criteria, 28 retrospective studies were included. All were level IV evidence of case series and retrospective studies. Overall, this included 634 total patients and 292 patients with individual patient data. The primary outcomes studied were complication rates, mortality, and Musculoskeletal Tumor Society (MSTS) functional score. Secondary outcomes included complication rate subtypes, number of lengthening procedures, mean amount lengthened, and prevalence of limb length discrepancies. RESULTS: A total of 292 patients with individual patient data averaged 10.1 years at the surgery and had a mean follow-up of 67 months. Two hundred sixteen patients (74%) had tumors of the distal femur. MSTS scores averaged 80.3 and overall mortality was 22%. Patients with distal femur tumors averaged 4.4 lengthening procedures and 43 mm lengthened. Leg length discrepancy (LLD) was 36% overall, which increased with longer periods of follow-up (P<0.001). Overall complication and revision rate was 43%, increasing to 59% in patients with 5 to 10 years of follow-up, and 89% in patients with >10 years of follow-up. Minimally invasive prostheses had lower rates of complications than noninvasive prostheses (P=0.024), specifically mechanical complications (P=0.028), mostly because of increased rates of lengthening and device failure in the noninvasive models (21% vs. 4%, P=0.0004). CONCLUSIONS: Despite its limitations, which include entirely heterogenous and retrospective case series data, this systematic review provides clinicians with pooled summary data representing the largest summary of outcomes after reconstruction with expandable prostheses to date. This analysis can assist surgeons to better understand and educate their patients and their families on functional outcomes, mortality, and complication rates after limb-sparing reconstruction with expandable prostheses for primary bone malignancies. LEVEL OF EVIDENCE: Level IV-retrospective case series with pooled data.


Assuntos
Membros Artificiais , Neoplasias Ósseas/cirurgia , Neoplasias Femorais/cirurgia , Salvamento de Membro/métodos , Osteossarcoma/cirurgia , Adolescente , Alongamento Ósseo , Criança , Pré-Escolar , Análise de Dados , Feminino , Fêmur/cirurgia , Seguimentos , Humanos , Desigualdade de Membros Inferiores/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
11.
Orthopedics ; 42(6): 349-354, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505018

RESUMO

There are conflicting reports regarding the efficacy of Major League Baseball (MLB) pitchers following medial ulnar collateral ligament reconstruction (UCLR). As advanced baseball metrics have revolutionized the way general managers define pitchers' value, the authors believe that these should be used to measure clinical outcomes after UCLR. All MLB pitchers who underwent UCLR from April 1, 1991, through July 1, 2016, were compiled (N=253). Pitcher demographics and statistics were collected for up to 3 full seasons preceding and following surgery. Data for pitching controls (all MLB [AMLB] pitchers) were also collected (N=14,756). Prior to surgery, pitchers with UCLR were significantly better than the AMLB pitchers in nearly all advanced value-based statistics: higher wins above replacement (WAR; 0.93 vs 0.78; 95% confidence interval [CI], 0.80-1.06), lower fielding independent pitching (FIP; 4.23 vs 4.51; 95% CI, 4.12-4.34), lower expected fielding independent pitching (xFIP; 4.17 vs 4.38; 95% CI, 4.06-4.28), higher win probability added (WPA; 0.21 vs 0.05; 95% CI, 0.1-0.32), and higher leverage index (pLI; 1.03 vs 0.96; 95% CI, 0.99-1.06). Pitchers who returned to play after UCLR demonstrated significantly lower value with worse WAR, FIP, WPA, and pLI (P<.05). Conversely, after excluding pitchers who failed to achieve a sustained return to play of greater than 1 year, there were no significant decreases in value after surgery. The authors conclude that, prior to injury, pitchers who have UCLR are more valuable than average MLB pitchers. However, UCLR pitchers perform worse when compared with their presurgical values. This may be affected by players not being able to continue their careers for more than 1 year. [Orthopedics. 2019; 42(6):349-354.].


Assuntos
Desempenho Atlético/fisiologia , Beisebol/lesões , Articulação do Cotovelo/cirurgia , Reconstrução do Ligamento Colateral Ulnar , Adulto , Bases de Dados Factuais , Humanos , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Rotação
12.
Orthop J Sports Med ; 7(2): 2325967119826540, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30815499

RESUMO

BACKGROUND: Medial ulnar collateral ligament (UCL) reconstruction is a common procedure performed among Major League Baseball (MLB) pitchers. The etiology of UCL injury is complex and is not entirely understood. HYPOTHESIS: To better understand risk factors for requiring UCL reconstruction, we hypothesized that pitchers who eventually undergo the procedure will exhibit different throwing mechanics as measured by pitch-tracking data points, such as velocity and release location. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Pitch-tracking and demographic data were gathered for 140 MLB pitchers who had undergone UCL reconstruction between the 2010 and 2017 seasons. Pitch type, release location, and velocity were compared between the surgical cohort and a matched-control cohort. RESULTS: When compared with controls, the mean pitch release location for pitchers who required UCL reconstruction was 12.2 cm more lateral in the year immediately preceding surgery (P = .001). Furthermore, within the surgical cohort, the horizontal release location was 3.4 cm more lateral immediately preceding surgery compared with 2 years earlier (P = .036). Binary logistic regression indicated an odds ratio of 0.51, suggesting a roughly 5% increased odds of UCL reconstruction for every 10 cm of increased lateral release location (P = .048). Both the surgical and the control cohorts threw similar rates of fastballs and had similar mean pitch velocity and fastball velocity. Control pitchers displayed a significant decrease over time in mean pitch velocity (P = .005) and mean fastball velocity, while pitchers in the UCL reconstruction cohort did not (P = .012). CONCLUSION: Pitch tracking indicates that the mean release point is more lateral in pitchers preceding UCL reconstruction as compared with controls, suggesting that a more lateral pitch release location is an independent risk factor for UCL injury and reconstruction.

13.
J Shoulder Elbow Surg ; 26(8): 1307-1315, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28734533

RESUMO

BACKGROUND: Medial ulnar collateral ligament (UCL) reconstruction is a common procedure performed on Major League Baseball pitchers. Variations in pitching mechanics before and after UCL reconstructive surgery are not well understood. METHODS: Publicly available pitch tracking data (PITCHf/x) were compared for all Major League Baseball pitchers who underwent UCL reconstruction between 2008 and 2013. Specific parameters analyzed were fastball percentage, release location, velocity, and movement of each pitch type. These data were compared before and after UCL reconstructive surgery and compared with a randomly selected control cohort. RESULTS: There were no statistically significant changes in pitch selection or pitch accuracy after UCL reconstruction, nor was there a decrease in pitch velocity. The average pitch release location for 4-seam and 2-seam fastballs, curveballs, and changeups is more medial after UCL reconstruction (P < .01). Four-seam fastballs and sliders showed decreased horizontal breaking movement after surgery (P < .05), whereas curveballs showed increased downward breaking movement after surgery (P < .05). CONCLUSIONS: Pitch selection, pitch velocity, and pitch accuracy do not significantly change after UCL reconstruction, nor do players who require UCL reconstruction have significantly different pitch selection, velocity, or accuracy than a randomly selected control cohort. Pitch release location is more medial after UCL reconstruction for all pitch types except sliders. Breaking movement of fastballs, sliders, and curveballs changes after UCL reconstruction.


Assuntos
Desempenho Atlético/estatística & dados numéricos , Beisebol/fisiologia , Movimento/fisiologia , Reconstrução do Ligamento Colateral Ulnar , Adulto , Fenômenos Biomecânicos/fisiologia , Estudos de Casos e Controles , Articulação do Cotovelo/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
14.
PLoS One ; 11(8): e0160982, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27513663

RESUMO

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signals during cellular stress via several post-translational modifications that change its folding properties, protein-protein interactions and sub-cellular localization. We examined GAPDH properties in acute mouse liver injury due to ethanol and/or acetaminophen (APAP) treatment. Synergistic robust and time-dependent nuclear accumulation and aggregation of GAPDH were observed only in combined, but not individual, ethanol/APAP treatments. The small molecule GAPDH-targeting compound TCH346 partially attenuated liver damage possibly via mitochondrial mechanisms, and independent of nuclear accumulation and aggregation of GAPDH. These findings provide a novel potential mechanism for hepatotoxicity caused by combined alcohol and acetaminophen exposure.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Etanol/toxicidade , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Fígado/efeitos dos fármacos , Oxepinas/farmacologia , Transporte Proteico/efeitos dos fármacos , Analgésicos não Narcóticos/toxicidade , Animais , Núcleo Celular/metabolismo , Depressores do Sistema Nervoso Central/toxicidade , Sinergismo Farmacológico , Feminino , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
15.
Mol Biol Cell ; 27(20): 3005-3012, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27535425

RESUMO

Liver disease progression is modulated by genetic modifiers in mouse strains and across human races and ethnicities. We hypothesized that hepatocyte culture duration and genetic background regulate hepatocyte susceptibility to apoptosis. Hepatocytes were isolated from FVB/N, C57BL/6, and C3H/He mice and cultured or treated with Fas ligand or acetaminophen after different culture times. Protein and mRNA expressions of Fas receptor, caspases-3/7/8, and Bak/Bax/Bid proteins were determined. FVB/N hepatocytes manifested rapid decreases of caspases-3/7 but not caspase-8 as culture time increased, which paralleled decreased susceptibility to apoptosis. Some changes were also found in Fas-receptor and Bak, Bax, and Bid proteins; caspase mRNA decreases were also noted. Caspase protein degradation was partially reversed by lysosomal protease but not proteasome or autophagy inhibitors. C57BL/6 and FVB/N hepatocytes behaved similarly in their limited susceptibility to apoptosis, whereas C3H/He hepatocytes show limited alterations in caspases, with consequent increased susceptibility to apoptosis. Similarly, C3H/He mice were more susceptible than C57BL/6 and FVB/N mice to Fas-mediated liver injury. Therefore there are significant mouse strain-dependent differences in susceptibility to apoptosis and selective loss of caspases upon short-term hepatocyte culture, with consequent decrease in susceptibility to apoptosis. These differences likely reflect genetic modifiers that provide resistance or predisposition to hepatocyte death.


Assuntos
Apoptose/fisiologia , Patrimônio Genético , Receptor fas/genética , Receptor fas/metabolismo , Acetaminofen , Animais , Apoptose/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Caspase 3/metabolismo , Caspase 7/metabolismo , Caspase 8/metabolismo , Técnicas de Cultura de Células , Proteína Ligante Fas/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C3H/genética , Camundongos Endogâmicos C57BL/genética , Transdução de Sinais/fisiologia , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
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