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1.
Apoptosis ; 18(5): 566-77, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23456624

RESUMO

Apoptotic injury participates in hepatic fibrosis, but the molecular mechanisms are not well understood. The present study aimed to investigate the role of inducible TIMP1 in the pathogenesis of hepatic apoptosis-fibrosis. Apoptosis was induced with GCDC, LPS, and alcohol in precision-cut liver slices or bile duct ligation (BDL) in rats, as reflected by caspase-3 activity, TUNEL assay, and apoptosis-related gene profiles. The hepatic fibrosis was detected with Picrosirius staining, hydroxyproline determination, and expression profiling of fibrosis-related genes. Levels of TIMP1 were upregulated by the hepatic apoptosis, but downregulated by caspase inhibitor. The inducible TIMP1 was apoptosis-dependent. Once TIMP1 was inhibited with treatment of TIMP1-siRNA, the fibrotic response was reduced as demonstrated by hydroxyproline assay. In addition, the expression of fibrosis-related genes aSMA, CTGF, and TGFb2r were down-regulated subsequent to the treatment of TIMP1-siRNA. TIMP1 could mediate the expression of fibrosis-related genes. TIMP1 was transcriptionally regulated by nuclear factor c-Jun as demonstrated by EMSA and ChIP assay. The treatment of c-Jun siRNA could significantly decrease the expression of TIMP1 induced by alcohol, GCDC, or LPS treatment. Hepatic apoptosis induces the expression of TIMP1. Inducible TIMP1 can modulate the expression of fibrosis-related genes in liver. TIMP1 pathway is a potential target for therapeutic intervention of fibrotic liver diseases.


Assuntos
Apoptose/genética , Cirrose Hepática/metabolismo , Fígado/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Actinas/genética , Actinas/metabolismo , Animais , Biomarcadores/metabolismo , Inibidores de Caspase/farmacologia , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Etanol , Regulação da Expressão Gênica , Ácido Glicoquenodesoxicólico , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Microtomia , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Técnicas de Cultura de Tecidos , Inibidor Tecidual de Metaloproteinase-1/antagonistas & inibidores , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta2/metabolismo
2.
Cell Signal ; 25(4): 867-74, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23275033

RESUMO

UNLABELLED: Hepatocyte apoptosis is a ubiquitous feature of chronic liver injury, but the molecular mechanism remains to be determined. The liver-enriched Foxa2 transcription factor has been implicated in inflammation and neoplasia. Foxa2 may play a role in the regulation of apoptosis. This study aimed to investigate the relationship between Foxa2 and hepatic apoptosis. Apoptosis was induced with different causative factors as measured by caspase activity and TUNEL assay. Results showed that the apoptotic injury was associated with a downregulation of Foxa2. Foxa2-expressing vectors decreased apoptosis, whereas siRNA silencing of Foxa2 increased apoptosis in HepG2 cells. Foxa2 was correlated with expression profiling of anti-apoptotic genes cIAP1, cIAP2, XIAP, and survivin. Significantly, the cIAP1 expression was decreased by siRNA silencing of Foxa2, but increased by Foxa2-expressing vectors. The promoter of cIAP1 had specific DNA sequences that could be bound by Foxa2 nuclear protein as demonstrated by EMSA and gel supershift assay. The cIAP1 promoter was also occupied by Foxa2 nuclear factor through ChIP assay. Deletion of putative Foxa2 binding domains in cIAP1 promoter significantly reduced its promoter activity. CONCLUSION: A mechanism by which Foxa2 transcription factor modulates hepatic apoptosis may be through cIAP1 signaling pathway. Foxa2 can be a potential target for therapeutic intervention in liver diseases.


Assuntos
Apoptose , Fator 3-beta Nuclear de Hepatócito/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Ensaio de Desvio de Mobilidade Eletroforética , Células Hep G2 , Fator 3-beta Nuclear de Hepatócito/antagonistas & inibidores , Fator 3-beta Nuclear de Hepatócito/genética , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Proteínas Inibidoras de Apoptose/genética , Fígado/lesões , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Survivina , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
3.
J Bone Joint Surg Am ; 94(23): 2167-75, 2012 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-23224387

RESUMO

BACKGROUND: Glenoid component malposition for anatomic shoulder replacement may result in complications. The purpose of this study was to define the efficacy of a new surgical method to place the glenoid component. METHODS: Thirty-one patients were randomized for glenoid component placement with use of either novel three-dimensional computed tomographic scan planning software combined with patient-specific instrumentation (the glenoid positioning system group), or conventional computed tomographic scan, preoperative planning, and surgical technique, utilizing instruments provided by the implant manufacturer (the standard surgical group). The desired position of the component was determined preoperatively. Postoperatively, a computed tomographic scan was used to define and compare the actual implant location with the preoperative plan. RESULTS: In the standard surgical group, the average preoperative glenoid retroversion was -11.3° (range, -39° to 17°). In the glenoid positioning system group, the average glenoid retroversion was -14.8° (range, -27° to 7°). When the standard surgical group was compared with the glenoid positioning system group, patient-specific instrumentation technology significantly decreased (p < 0.05) the average deviation of implant position for inclination and medial-lateral offset. Overall, the average deviation in version was 6.9° in the standard surgical group and 4.3° in the glenoid positioning system group. The average deviation in inclination was 11.6° in the standard surgical group and 2.9° in the glenoid positioning system group. The greatest benefit of patient-specific instrumentation was observed in patients with retroversion in excess of 16°; the average deviation was 10° in the standard surgical group and 1.2° in the glenoid positioning system group (p < 0.001). Preoperative planning and patient-specific instrumentation use resulted in a significant improvement in the selection and use of the optimal type of implant and a significant reduction in the frequency of malpositioned glenoid implants. CONCLUSIONS: Novel three-dimensional preoperative planning, coupled with patient and implant-specific instrumentation, allows the surgeon to better define the preoperative pathology, select the optimal implant design and location, and then accurately execute the plan at the time of surgery.


Assuntos
Artroplastia de Substituição/métodos , Diagnóstico por Computador/instrumentação , Imageamento Tridimensional/métodos , Articulação do Ombro/diagnóstico por imagem , Software , Idoso , Feminino , Seguimentos , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Desenho de Prótese , Radiografia , Amplitude de Movimento Articular/fisiologia , Medição de Risco , Articulação do Ombro/fisiopatologia , Articulação do Ombro/cirurgia , Instrumentos Cirúrgicos/normas , Resultado do Tratamento
4.
Cell Signal ; 23(10): 1677-85, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21693187

RESUMO

Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) can ameliorate apoptosis induced by toxic glycochenodeoxycholate (GCDC) in hepatocytes. However, the underlying molecular mechanisms are not yet understood in detail. This study is to clarify the function of iNOS/NO and its mechanisms during the apoptotic process. The apoptosis was brought about by GCDC in rat primary hepatocytes. iNOS/NO signaling was then investigated. iNOS inhibitor 1400W enhanced the GCDC-induced apoptosis as reflected by caspase-3 activity and TUNEL assay. Exogenous NO regulated the apoptosis subsequent to NO donor S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). The GCDC-induced apoptosis was decreased with 0.1mM SNAP or 0.15mM SNP, while it was increased with 0.8mM SNAP or 1.2mM SNP. The endogenous iNOS inhibited apoptosis, but the exogenous NO played a dual role during the GCDC-induced apoptosis. There was a potential iNOS/Akt/survivin axis that inhibited the hepatocyte apoptosis in low doses of NO donors. In contrast, high doses of NO donors activated CHOP through p38MAP-kinase (p38MAPK), upregulated TRAIL receptor DR5, and suppressed survivin. Consequently the high doses of NO donors promoted the apoptosis in hepatocytes. Our data suggest that the iNOS/NO signaling can modulate Akt/survivin and p38MAPK/CHOP pathways to mediate the GCDC-induced the apoptosis in hepatocytes. These signaling pathways may serve as targets for therapeutic intervention in cholestatic liver disease.


Assuntos
Apoptose , Ácido Glicoquenodesoxicólico/farmacologia , Hepatócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/farmacologia , Transdução de Sinais , Amidinas/farmacologia , Animais , Benzilaminas/farmacologia , Western Blotting , Células Cultivadas , Ensaio de Desvio de Mobilidade Eletroforética , Inibidores Enzimáticos/metabolismo , Hepatócitos/metabolismo , Imidazóis/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Nitroprussiato/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , S-Nitroso-N-Acetilpenicilamina/farmacologia , Survivina , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Biochim Biophys Acta ; 1813(8): 1395-403, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21539866

RESUMO

Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) involve many pathophysiologic conditions. The expression of iNOS is regulated at multiple stages. Presently, the regulatory details of iNOS signaling are still unclear. This study aimed to investigate the regulatory role of C/EBPα and C/EBPß in iNOS signaling pathway. By employing the techniques such as EMSA, ChIP assay, site-directed mutagenesis, and siRNA silencing, the relationship between iNOS and C/EBPα/C/EBPß in rat hepatocytes was clarified. iNOS promoter was the direct transcriptional targets of the C/EBPα, C/EBPß, and NF-κB binding proteins. There was the interactive influence between NF-κB and C/EBPα/C/EBPß. The expression of iNOS was modulated by C/EBPα/C/EBPß transcription factors. Moreover, the iNOS expression mediated glycochenodeoxycholate (GCDC)-induced apoptosis in hepatocytes. C/EBPα/C/EBPß binding proteins could affect the GCDC-induced apoptosis through iNOS cascade. These findings indicate that C/EBPα and C/EBPß regulate the iNOS expression, which may further modify cell responses such as apoptosis and cell survival.


Assuntos
Apoptose/fisiologia , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Sítios de Ligação/genética , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas de Transporte/metabolismo , Primers do DNA/genética , Ácido Glicoquenodesoxicólico/farmacologia , Hepatócitos/efeitos dos fármacos , Técnicas In Vitro , Mutagênese Sítio-Dirigida , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Regiões Promotoras Genéticas , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
7.
Biochim Biophys Acta ; 1803(12): 1368-75, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20816704

RESUMO

UNLABELLED: Hepatocytes in primary culture undergo apoptosis upon exposure to glycochenodeoxycholate (GCDC). The signaling mechanisms of GCDC-induced apoptosis remain unclear. To investigate the role of antiapoptotic genes, we compared apoptotic response in primary hepatocytes following GCDC treatment. The hepatocytes from adult Sprague-Dawley rats were cultured in collagen-coated dishes and treated with GCDC in varying concentrations, or the same concentration at different time intervals. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, DNA fragmentation assay, and caspase assays. Expression of apoptosis-related genes and proteins was evaluated by RT-PCR, quantitative real-time PCR (qRT-PCR), and Western blotting, respectively. The DNA-binding property of a nuclear protein was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. An interesting result was that GCDC caused hepatocyte apoptosis to display a biphasic phenomenon at a dosage of 50µM, whereas it was not found at higher dosages such as 200µM. GCDC stimulated the expression of antiapoptotic Survivin, which also presented a biphasic response. The activation of nuclear factor-kappaB (NF-κB) corresponded with the up-regulation of Survivin. The inhibitor of NF-κB, BAY 11-7082, suppressed the expression of Survivin and simultaneously eliminated the biphasic response. The expression of Survivin was transcriptionally mediated by the activation of NF-κB, as shown by EMSA and ChIP assay. CONCLUSIONS: These results demonstrated that a low dosage of GCDC induced the hepatocyte apoptosis to exhibit the biphasic response, which was regulated by the expression of Survivin through NF-κB signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Glicoquenodesoxicólico/toxicidade , Proteínas Associadas aos Microtúbulos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Ratos , Ratos Sprague-Dawley , Survivina
8.
J Shoulder Elbow Surg ; 19(8): 1243-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20558091

RESUMO

HYPOTHESIS: This study evaluated the intra-rater and inter-rater correlation of 3 commonly used x-ray image classifications and defined the clinical factors most correlated with a surgical recommendation for a hemiarthroplasty or a reverse total shoulder arthroplasty (RSA) for treatment of rotator cuff tear arthropathy (CTA). We hypothesized that specific radiographic criteria and clinical criteria would be most important and consistently used among experienced shoulder surgeons when determining the best surgical option for a particular patient. METHODS: Four experienced orthopedic surgeons evaluated standard anteroposterior radiographs and the clinical examination of 37 shoulders with CTA. On each reading, they classified the grade of pathology using the Seebauer, Favard, and Hamada classifications. Using radiographic criteria alone, or with the clinical findings, each evaluator determined the recommended prosthetic treatment for each shoulder. RESULTS: Intra-rater correlations for surgical recommendations using radiographic criteria ranged from 0.39 to 1.0 and improved in 3 of 4 evaluators when the clinical examination was included in the clinical decision. The inter-rater reliability using these same criteria were fair, at 0.32 for radiographic and .35 for radiographic and clinical data. The most significant radiographic factors associated with a surgical decision were the degree of humeral head superior migration and the escape of the humeral head from the coracoacromial arch. Clinical factors most associated with the decision for RSA were advanced age, loss of shoulder elevation, superior humeral head escape, and pseudoparalysis of the shoulder. Radiographic findings had a less significant effect on surgical recommendations when clinical factors were included. CONCLUSION: Clinical and radiographic criteria are needed for a decision for hemiarthroplasty or RSA in the treatment of CTA. A treatment algorithm based upon radiographic and clinical criteria is proposed.


Assuntos
Artrite/diagnóstico por imagem , Lesões do Manguito Rotador , Idoso , Idoso de 80 Anos ou mais , Artrite/classificação , Artrite/cirurgia , Artroplastia , Artroplastia de Substituição , Tomada de Decisões , Feminino , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Radiografia , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem
9.
J Bone Joint Surg Am ; 90(11): 2438-45, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18978413

RESUMO

BACKGROUND: Arthritic changes to glenoid morphology can be difficult to fully characterize on both plain radiographs and conventional two-dimensional computer tomography images. We tested the hypothesis that three-dimensional imaging of the shoulder would increase inter-rater agreement for assessing the extent and location of glenoid bone loss and also would improve surgical planning for total shoulder arthroplasty. METHODS: Four shoulder surgeons independently and retrospectively reviewed the preoperative computed tomography scans of twenty-four arthritic shoulders. The blinded images were evaluated with conventional two-dimensional imaging software and then later with novel three-dimensional imaging software. Measurements and preoperative judgments were made for each shoulder with use of each imaging modality and then were compared. The glenoid measurements were glenoid version and bone loss. The judgments were the zone of maximum glenoid bone loss, glenoid implant fit within the glenoid vault, and how to surgically address abnormal glenoid version and bone loss. Agreement between observers was evaluated with use of intraclass correlation coefficients and the weighted kappa coefficient (kappa), and we determined if surgical decisions changed with use of the three-dimensional data. RESULTS: The average glenoid version (and standard deviation) measured -17 degrees +/- 2.2 degrees on the two-dimensional images and -19 degrees +/- 2.4 degrees on the three-dimensional images (p < 0.05). The average posterior glenoid bone loss measured 9 +/- 2.3 mm on the two-dimensional images and 7 +/- 2 mm on the three-dimensional images (p < 0.05). The average anterior bone loss measured 1 mm on both the two-dimensional and the three-dimensional images. However, the intraclass correlation coefficients for anterior bone loss increased significantly with use of the three-dimensional data (from 0.36 to 0.70; p < 0.05). Observers were more likely to locate mid-anterior glenoid bone loss on the basis of the three-dimensional data (p < 0.05). The use of three-dimensional data provided greater agreement among observers with regard to the zone of glenoid bone loss, glenoid prosthetic fit, and surgical decision-making. Also, when the judgment of implant fit changed, observers more often determined that it would violate the vault walls on the basis of the three-dimensional data (p < 0.05). CONCLUSIONS: The use of three-dimensional imaging can increase inter-rater agreement for the analysis of glenoid morphology and preoperative planning. Important considerations such as the extent and location of glenoid bone loss and the likelihood of implant fit were influenced by the three-dimensional data.


Assuntos
Artroplastia de Substituição/métodos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Estudos Retrospectivos
10.
J Shoulder Elbow Surg ; 17(4): 575-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18440832

RESUMO

To our knowledge, no independent analysis of the inter-rater agreement of the widely used Walch classification for osteoarthritic glenoid morphology has been performed. The computed tomography scans of 24 shoulders with primary osteoarthritis were used by 4 experienced shoulder surgeons to classify the glenoids independently according to Walch et al. The weighted kappa statistic was calculated to determine the inter-rater and intrarater agreement among observers. The overall inter-rater agreement for the Walch classification was fair (kappa = 0.37) when classified into the 5 types (A1, A2, B1, B2, and C). Agreement for the various subclassifications was as follows: A1, kappa = 0.22; A2, kappa = 0.33; B1, kappa = 0.17; B2, kappa = 0.32; and C, kappa = 0.86. When the classification system was simplified to just the 3 major types (A, B, and C), overall agreement was moderate (kappa = 0.44). Agreement for each type was moderate for A (kappa = 0.59) and B (kappa = 0.59) and almost perfect for C (kappa = 0.89). Overall intrarater agreement was fair (kappa = 0.37). We conclude that only fair agreement was found among experienced shoulder surgeons when classifying arthritic shoulders using the classification system of Walch et al. A glenoid classification scheme that relies more upon glenoid morphology and less upon humeral head position may demonstrate greater observer agreement and, therefore, may offer greater value.


Assuntos
Artrite Reumatoide/classificação , Osteoartrite/classificação , Articulação do Ombro/diagnóstico por imagem , Idoso , Artrite Reumatoide/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoartrite/diagnóstico por imagem , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
11.
J Shoulder Elbow Surg ; 17(2): 328-35, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18218326

RESUMO

The 3-dimensional (3D) shape of the glenoid vault has been defined previously and shown to be a complex, yet consistent, shape in individuals without glenoid pathology. We proposed assessing whether this conserved shape could be used as a template to measure glenoid bone loss in subjects with glenohumeral osteoarthritis. Computed tomography (CT) scans of both shoulders were obtained from 12 subjects with unilateral glenohumeral osteoarthritis. The paired scapulae were reconstructed 3-dimensionally, using a previously developed graphic software package. Two methods of estimating glenoid bone loss were performed. First, using the software, a stereolithography model of the standardized vault shape was implanted into each glenoid and measurements made of the volume of the implant not contained within each vault. Second, direct measurements of the paired glenoid vault volumes were performed. The volume of the nonarthritic glenoid was used as a subject-specific template for normal glenoid vault volume for each pair. The glenoid bone volumes measured by each method were compared and Pearson's correlation coefficient determined. The average measurement of glenoid bone loss using the vault implant was within 0.8% (SD +/- 1.5%) of the measurement made using the contralateral, normal glenoid. For all patients, Pearson's correlation coefficient was .99, indicating a very high correlation between the two methods of measuring bone loss (P < .0001). The intricate, yet consistent 3D shape of the glenoid vault can be used as an accurate and reliable template to measure glenoid bone loss in glenohumeral osteoarthritis.


Assuntos
Doenças Ósseas/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Articulação do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade
13.
J Bone Joint Surg Am ; 88(6): 1238-44, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16757756

RESUMO

BACKGROUND: Evidence to justify the use of porcine small intestine submucosa to augment repairs of large and massive rotator cuff tears is based on favorable results found in studies of Achilles tendon and infraspinatus tendon repairs in canines. The purpose of this study was to determine the effectiveness of a small intestine submucosal patch to augment the repair of chronic two-tendon rotator cuff tears in humans. METHODS: Thirty shoulders with a chronic two-tendon rotator cuff tear that was completely repairable with open surgery were randomized to be treated with either augmentation with porcine small intestine mucosa or no augmentation. All patients completed a PENN shoulder-score questionnaire preoperatively and at the time of the latest follow-up (at an average of fourteen months). Magnetic resonance imaging showed that nine shoulders had a large tear and twenty-one had a massive tear. All patients underwent a magnetic resonance imaging scan with intra-articular gadolinium one year after the repair to assess the status of the rotator cuff. RESULTS: The rotator cuff healed in four of the fifteen shoulders in the augmentation group compared with nine of the fifteen in the control group (p = 0.11). The median postoperative PENN total score was 83 points in the augmentation group compared with 91 points in the control group (p = 0.07). Healing of the defects in both groups demonstrated a strong correlation with the patients' clinical scores. The median postoperative PENN total score was 96 points in the group with a healed repair and 81 points in the group with a failed repair (p = 0.007). The percentage change between the preoperative and postoperative patient satisfaction scores was 400% in the group with a healed repair, and 50% in the group with a failed repair (p = 0.04). CONCLUSIONS: Augmentation of the surgical repair of large and massive chronic rotator cuff tears with porcine small intestine submucosa did not improve the rate of tendon-healing or the clinical outcome scores. On the basis of these data, we do not recommend using porcine small intestine submucosa to augment repairs of massive chronic rotator cuff tears done with the surgical and postoperative procedures described in this study.


Assuntos
Artroplastia de Substituição , Bioprótese , Lesões do Manguito Rotador , Manguito Rotador/cirurgia , Adulto , Idoso , Animais , Feminino , Seguimentos , Humanos , Mucosa Intestinal , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Recuperação de Função Fisiológica/fisiologia , Manguito Rotador/fisiopatologia , Suínos , Falha de Tratamento
15.
Clin Orthop Relat Res ; 442: 109-14, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16394748

RESUMO

UNLABELLED: A valgus impacted, four-part humerus fracture is an uncommon but important injury to recognize in patients with orthopaedic trauma. Recognizing this fracture pattern and understanding the pathoanatomy of it are essential to providing appropriate care. The treatment options for valgus impacted, four-part humerus fractures range from nonoperative care to hemiarthroplasty. The peer-reviewed literature provides insight into the important factors to consider in deciding how to treat patients with valgus impacted, four-part humerus fractures. Recently, less invasive surgical techniques have been reported as a way to preserve the blood supply to the articular fracture fragment, which decreases the risk of developing avascular necrosis. Even though these techniques are becoming more popular, they are not indicated for all patients. Surgeons must use an individualized approach for each patient with this fracture. Satisfactory results have been reported for the nonoperative and operative techniques used to treat valgus impacted, four-part humerus fractures. However, less invasive procedures may help to achieve a more favorable clinical outcome. Limiting the surgical approach and achieving stabilization with minimal fixation helps to preserve the viability of the humeral head and to prevent postoperative morbidity related to osseous and soft tissue healing. Hemiarthroplasty becomes a reasonable treatment option in older patients with substantial displacement of the fracture fragments and poor bone quality that would not support internal fixation. LEVEL OF EVIDENCE: Therapeutic study, level V (expert opinion). See Guidelines for Authors for a complete description of levels of evidence.


Assuntos
Fixação de Fratura/métodos , Fraturas do Ombro/terapia , Artroplastia/métodos , Tomada de Decisões , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Fraturas do Ombro/diagnóstico
16.
HPB (Oxford) ; 8(2): 142-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-18333263

RESUMO

INTRODUCTION: Traditional resections for pancreatic malignancies include distal pancreatectomy with splenectomy and pancrearicoduodenectomy (PD). Alternative resections for benign pancreatic disease are used to minimize the resection of normal pancreatic and splenic parenchyma. This study describes the use of central pancreatectomy (CP) in 10 patients. METHODS: A retrospective chart review of all patients undergoing CP between May 1999 and February 2004 was undertaken. RESULTS: Ten patients (eight female, two male) underwent CP for benign pancreatic disease. Median age was 59 years (range 21-75). Eight patients presented with abdominal pain, two of whom also had weight loss. One patient each presented with hypoglycemia and as an incidental finding. Median operative time was 255 min (range 160-380 min). Proximal pancreatic remnant was stapled in five and oversewn in five. Distal pancreatic remnant was managed with pancreaticojejunostomy in six patients and pancreatjcogastrostomy in four patients. There were no 30-day mortalities. Pancreatic fistula developed in four patients (40%), and all resolved without operative intervention. All patients are alive with no recurrence and no new endocrine or exocrine dysfunction. CONCLUSION: CP has similar morbidity and mortality rates to traditional pancreatic resections and may offer a lower incidence of diabetes and exocrine insufficiency.

18.
J Bone Joint Surg Am ; 87(4): 808-14, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15805211

RESUMO

BACKGROUND: Posterior glenoid bone loss is often seen in association with glenohumeral osteoarthritis. This posterior asymmetric wear can lead to retroversion of the glenoid component and posterior instability after total shoulder arthroplasty. Options for the treatment of this asymmetric wear include eccentric reaming of the so-called high side, bone-grafting, and/or anteverting the humeral component. Although anteverting the humeral component has been advocated by many, it has not been substantiated on the basis of biomechanical data. The purpose of the present study was to determine whether anteverting the humeral component increases the stability of a total shoulder replacement with a retroverted glenoid component. METHODS: A total shoulder arthroplasty was performed in eight human cadaveric shoulders. The glenoid component was placed in 15 degrees of retroversion. Two humeral versions were tested for each specimen: anatomic version and 15 degrees of anteversion relative to anatomic version. The specimens were mounted supine in a custom fixture on a servohydraulic testing system. The humerus was translated posteriorly by one-half of the width of the glenoid. Three positions of humeral rotation were tested for each position of humeral version. Both the energy and the peak load were analyzed as measures of joint stability. RESULTS: There was no significant difference in either energy or peak load between the tests performed with the humeral component in 15 degrees of anteversion and those performed with the component in anatomic version in any of the three rotational positions (p > 0.05). CONCLUSIONS: Although anteverting the humeral component during total shoulder arthroplasty to compensate for glenoid retroversion has been advocated, these data suggest that compensatory anteversion of the humeral component does not increase the stability of a shoulder replacement with a retroverted glenoid component.


Assuntos
Artroplastia de Substituição/métodos , Instabilidade Articular/prevenção & controle , Osteoartrite/cirurgia , Articulação do Ombro/cirurgia , Idoso , Artroplastia de Substituição/efeitos adversos , Fenômenos Biomecânicos , Cadáver , Humanos , Instabilidade Articular/etiologia , Instabilidade Articular/fisiopatologia , Prótese Articular , Luxação do Ombro/etiologia , Luxação do Ombro/prevenção & controle
19.
J Biol Chem ; 280(25): 23490-5, 2005 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-15767249

RESUMO

The accumulation of glycochenodeoxycholate (GCDC) induced hepatocyte apoptosis in cholestasis. However, many hepatocytes still survived GCDC-induced apoptosis. The molecular mechanism for the survival of hepatocytes remains unclear. In the present study, isolated rat hepatocytes were cultured in William's E medium and treated with 50 microM GCDC. DNA, RNA, cell lysate, and nuclear proteins were collected at different intervals for DNA fragmentation assay, reverse transcription PCR, Western blotting, and gel mobility shift assay, respectively. GCDC-induced active caspases were detected as early as 2 h by Western blotting and kinetic caspase assay, whereas hepatocyte apoptosis was found at 4 h by DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling assay. When GCDC was removed, the increased caspases as well as NF-kappaB could be restored to control level. A1/Bfl-1 and inducible nitric oxide synthase (iNOS) were up-regulated in 2 h of GCDC stimulation. After GCDC was removed, hepatocytes decreased expression of A1/Bfl-1, but not iNOS, to the control level. NF-kappaB activation coincided with the change of A1/Bfl-1. Survivin, cIAP1, cIAP2, XIAP, and A1/Bfl-1, but not iNOS, were down-regulated by pan-caspase inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone. In addition, benzyloxycarbonyl-VAD-fluoromethyl ketone inhibited release of cytochrome c and suppressed NF-kappaB activation. Our data suggested that caspase pathway is an important regulatory factor during hepatocyte apoptosis. GCDC-induced caspase response is reversible, which may activate anti-apoptotic genes to protect hepatocytes from apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Hepatócitos/efeitos dos fármacos , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose/genética , Sequência de Bases , Inibidores de Caspase , Inibidores de Cisteína Proteinase/farmacologia , Primers do DNA , Ativação Enzimática , Hepatócitos/citologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
J Shoulder Elbow Surg ; 14(1): 85-90, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15723018

RESUMO

Preoperative evaluation for a total shoulder arthroplasty includes 2-dimensional analysis of the glenoid through either standard radiographs or computed tomography (CT) images. Recent evidence suggests that these 2-dimensional images may actually misrepresent the 3-dimensional (3D) anatomy of the glenoid. Because 3D reconstructions of CT images allow 3D visualization and analysis of the scapula as a free body, we hypothesized that they can reflect the true anatomy of the glenoid more accurately. To test this hypothesis, we obtained various glenoid morphometric measurements from excised cadaveric scapulae as well as their respective 3D CT images. On average, the glenoid version angles measured from the 3D CT images were within 1.0 degrees +/- 0.7 degrees (mean +/- SD) of those from the actual specimen (95% confidence limit, <2.2 degrees for all observers). These measurements from the 3D CT images showed high interobserver and intraobserver reliability (interobserver and intraobserver correlation coefficients, 0.983 and 0.978, respectively). Similarly, measured glenoid surface width and length from the 3D CT images were within 1.8 +/- 1.2 mm and 1.4 +/- 1.1 mm, respectively, of those from the actual specimen. In addition, we were able to estimate the glenoid surface area as well as the glenoid vault volume from the 3D CT images. These values were 8.67 +/- 2.73 cm2 and 11.86 +/- 5.06 cm3, respectively. The mean glenoid vault volume with respect to its surface area was 1.35 +/- 0.24 cm3/cm2 (range, 1.06-1.91 cm3/cm2). These data suggest that 3D CT images can accurately reflect the true anatomy of the glenoid and that they can provide valuable information regarding the glenoid surface and vault. As such, 3D CT images may prove to be a useful tool during the preoperative evaluation for a total shoulder arthroplasty, particularly in patients with significant glenoid bone loss.


Assuntos
Imageamento Tridimensional , Articulação do Ombro/anatomia & histologia , Articulação do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Antropometria , Cadáver , Humanos , Variações Dependentes do Observador
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