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1.
BMC Musculoskelet Disord ; 23(1): 679, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842588

RESUMO

BACKGROUND: Several physical examination tests and signs have been described to aid in the diagnosis of subscapularis (SSC) tear, but have limitations and variable sensitivity. This study aimed to introduce a novel test for detecting a leading-edge tear of the subscapularis (LETS), the most important tendinous portion of SSC. METHODS: A total of 233 patients who underwent arthroscopic repair for anterior and superior cuff tears between January 2018 to September 2019 were retrospectively reviewed. The provocative test we have coined as the "scissors sign" and the other related clinical tests (i.e., belly press, belly off, Napoleon, lift off, internal rotation lag, bear hug tests) were performed preoperatively. Whether the patient has a LETS or the complete tear of the SSC (CTS) was confirmed by arthroscopic findings. Sensitivity, specificity, and areas under the receiver operating characteristic curve were calculated for each test. RESULTS: In patients who had LETS with or without supraspinatus tear, the scissors sign showed the highest sensitivity (91.4%) with a specificity of 81.6%, positive predictive value (PPV) of 80.2%, and negative predictive value (NPV) of 92.1%. In patients with isolated LETS, the scissors sign also showed the highest sensitivity (90.3%) with a specificity of 81.6%, PPV of 57.1%, and NPV of 96.8%. The scissors sign for the complete tear of the subscapularis (CTS) with or without supraspinatus tear and the isolated CTS had a sensitivity of 73.1 and 75%, respectively. CONCLUSIONS: The scissors sign is a novel provocative test that can be helpful in the diagnosis of subscapularis tears, especially LETS, with its high sensitivity and diagnostic accuracy. In combination with other tests, the scissors sign will be a good screening tool.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Artroscopia , Humanos , Imageamento por Ressonância Magnética , Exame Físico , Estudos Retrospectivos , Lesões do Manguito Rotador/diagnóstico , Lesões do Manguito Rotador/cirurgia , Ruptura
2.
J Orthop Sci ; 27(6): 1257-1262, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34696922

RESUMO

BACKGROUND: Femoral revision surgery in patients with substantial bone loss is challenging. Impaction bone grafting using a cemented stem can be a good solution for reconstruction of the femur with poor bone stock and extensive bone loss. This study aimed to evaluate the mid-to-long-term clinical and radiographic results of impaction bone grafting using a cemented stem for Paprosky IV femoral bone defects. METHODS: Thirteen patients (13 hips) who underwent revision total hip arthroplasty with impaction bone grafting using a cemented stem and were followed up for at least 5 years were enrolled in this study. In all patients, a sufficient amount of fresh frozen bone of good quality was used. When cortical segmental defects were present, peripheral reinforcement with metal mesh and strut allograft was performed. The average follow-up duration was 11.1 (range, 5.3-15.1) years. The clinical and radiographic outcomes were reviewed at the final follow-up. RESULTS: The average Harris hip score was 82.5 (range, 79-94), and the average University of California, Los Angeles activity score was 5.6 (range, 4-8) at the final follow-up. Radiographic assessment revealed an average femoral component subsidence level of 0.67 (range, 0.05-2.81) mm. There were no complications, except one case (7.6%) of periprosthetic fracture. CONCLUSIONS: Impaction bone grafting using a cemented stem yielded excellent mid-to-long-term outcomes. It is a reliable technique for Paprosky IV femoral bone defects, and even when severe femoral cortical bone defects are present, long-term stability can be obtained using a metal mesh and/or strut allograft.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Transplante Ósseo/métodos , Falha de Prótese , Artroplastia de Quadril/métodos , Fêmur/cirurgia , Reoperação , Aloenxertos , Seguimentos , Resultado do Tratamento
3.
Materials (Basel) ; 14(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34771809

RESUMO

The purpose of this study was to predict the adhesive behavior of steel and carbon-fiber-reinforced plastic (CFRP) hybrid parts based on the cohesive zone model (CZM). In this study, the steel sheet and CFRP were joined by epoxy resin in the CFRP prepreg during the curing process, which could generate delamination at their interface because of the springback of steel or the thermal contraction of the CFRP. First, double cantilever beam (DCB) and end-notched flexure (ENF) tests were performed to obtain various adhesion properties such as the critical energy release rate of mode I, mode II (GI, GII), and critical stress (σmax). A finite element (FE) simulation was performed to predict delamination using CZM, which was also used to describe the interfacial behavior between the steel sheet and the CFRP. Finally, a U-shape drawing test was performed for the steel/CFRP hybrid parts, and these results were compared with analytical results.

4.
Geriatr Orthop Surg Rehabil ; 12: 21514593211015104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178416

RESUMO

PURPOSE: To introduce the principles and procedure of percutaneous elastic intramedullary nailing (PEIN) as a treatment for symptomatic incomplete atypical femoral fracture (SIAFF). METHODS: From October 2014 to April 2019, 6 cases of SIAFF were treated with PEIN. Two pre-bent 4-mm stainless-steel nails were used to apply compressive force to the fracture site. The antegrade method was used for proximal fractures and the retrograde method for middle and distal femoral fractures. The femoral bowing angle in the coronal and sagittal planes, and the time required for callus formation and union, were evaluated on plain radiographs in both planes. Thigh pain, tenderness, and complications were also assessed. RESULTS: The mean operating time was 65.00 ± 22.64 min. No case progressed to complete atypical fracture. In one case, fracture occurred around the point of nail entry after the patient fell from a chair on postoperative day 7. The incomplete fracture lines were united in 5 cases, after excluding one case with a complication. The time taken to confirm endocortical callus formation, fracture line disappearance, and clinical union was 2.11 ± 0.53, 6.45 ± 4.10, and 6.45 ± 3.65 months, respectively. CONCLUSIONS: PEIN is a quick, simple but effective treatment for SIAFF that considers the fracture mechanism and is applicable to cases with severe femoral bowing. LEVEL OF EVIDENCE: Level IV, case series.

5.
Materials (Basel) ; 14(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799688

RESUMO

Residual stress may influence the mechanical behavior and durability of drawn materials. Thus, this study develops a multiple reduction die (MRD) that can reduce residual stress during the drawing process. The MRD set consists of several die tips, die cases, and lubricating equipment. All the die tips of the MRD were disposed of simultaneously. Finite element analysis of the drawing process was performed according to the reduction ratio of each die tip, and the variables in drawing process with the MRD were optimized using a deep neural network to minimize the residual stress. Experiments on the drawing process with the conventional die and MRD were performed to evaluate the residual stress and verify the effectiveness of the MRD. The results of X-ray diffraction measurements indicated that the axial and hoop residual stresses on the surface were dramatically reduced.

6.
Arthroscopy ; 37(9): 2769-2779, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33892075

RESUMO

PURPOSE: To compare clinical and radiographic results of arthroscopic rotator cuff repair (ARCR) with biceps rerouting (BR) and those of conventional repair for semirigid, large-to-massive rotator cuff tear. METHODS: We prospectively collected data of 111 patients who underwent either ARCR + BR (n = 59, group 1) or only ARCR (n = 52, group 2) for semirigid, large-to-massive rotator cuff tear between January 2016 and December 2018. We comparatively analyzed both groups with respect to preoperative factors including concomitant lesions of the long head of the biceps tendon (LHBT). Univariate logistic regression analysis was performed to identify predictive variables for occurrence of retear after ARCR + BR. RESULTS: Mean age of groups 1 and 2 were 62.8 and 63.7 years, respectively (P = .484). Mean follow-up period in groups 1 and 2 were 15.1 and 25.1 months, respectively (P = .102). Mean range of motion and functional scores improved significantly (P < .05) and comparably (P > .05) in both groups. In total, 11 (18.6%) and 25 (48.1%) patients from groups 1 and 2, respectively, showed retear of the repaired rotator cuff at final follow-up (P < .01). Of 45 group 1 patients who showed less than 50% partial tearing of the LHBT preoperatively, 6 (13.3%) experienced retear. Comparatively, of 14 patients with partial tearing involving more than 50% of the LHBT, 5 (35.7%) suffered postoperative retear. If the patients had partial tear involving more than 50% of LHBT preoperatively, the odds ratio (OR) to have retear was 4.222 (P = .037). Wider (OR, 1.445, P = .047) and thinner (OR, 0.166, P = .019) LHBT were the prognostic factors to have retear. Three (5.1%) group 1 patients showed the Popeye deformity at final follow-up. CONCLUSIONS: ARCR + BR for semirigid, large-to-massive rotator cuff tears effectively improved clinical and structural outcomes as also shown in the conventional repairs. However, the retear rate was significantly lower in patients who underwent ARCR + BR than those treated conventionally. Partial tearing involving more than 50% of the LHBT and wide and/or thin tendon morphology were significant risk factors for postoperative occurrence of retear. LEVEL OF EVIDENCE: Level III, retrospective therapeutic comparative trial.


Assuntos
Lesões do Manguito Rotador , Artroscopia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Tendões
7.
J Shoulder Elbow Surg ; 30(8): e482-e492, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33359399

RESUMO

BACKGROUND: Studies on the effects of manipulation under anesthesia (MUA) for primary stiff shoulder when different comorbidities are present are lacking. Our aim was to assess how comorbidities influence the recovery speed and clinical outcomes after MUA. METHODS: Between April 2013 and September 2018, 281 consecutive primary stiff shoulders in the frozen phase treated with MUA were included in this study. We investigated the comorbidities of patients and divided them into the control (n = 203), diabetes mellitus (DM) (n = 32), hyperlipidemia (n = 26), and thyroid disorder (n = 20) groups. The range of motion (ROM) and clinical scores for each group before MUA and 1 week, 6 weeks, and 3 months after MUA were comparatively analyzed. We identified the ROM recovery time after MUA and the responsiveness to MUA. Then, subjects were subdivided into early and late recovery groups based on their recovery time and into successful and nonsuccessful MUA groups based on their responsiveness to MUA. RESULTS: Significant improvements in ROM and clinical scores at 3 months after MUA were observed in all groups. Significant differences in ROM among the 4 groups were also observed during follow-up (P < .05). The DM group had significantly lower ROM values, even at 3 months after MUA, compared with the control group. The ROM recovery speed after MUA was slowest in the DM group, followed by the thyroid disorder, hyperlipidemia, and control groups. Most (90.6%) of the DM group experienced late recovery. The proportion of nonsuccessful MUA was higher in the DM and thyroid disorder groups than that in the control and hyperlipidemia groups (P = .004). During follow-up, there were no differences among groups regarding the visual analog scale, University of California at Los Angeles shoulder, and Constant scores. CONCLUSION: The ROM recovery speed and responsiveness to MUA for primary stiff shoulder were poorer for the DM and thyroid disorder groups than for the control group. In particular, compared with any other disease, outcomes were poorer when the comorbidity was DM. If patients have comorbidities, then they should be informed before MUA that the comorbidity could affect the outcomes of treatment.


Assuntos
Anestesia , Bursite , Articulação do Ombro , Bursite/epidemiologia , Bursite/terapia , Comorbidade , Humanos , Manipulação Ortopédica , Amplitude de Movimento Articular , Ombro , Resultado do Tratamento
8.
Materials (Basel) ; 14(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375714

RESUMO

The multi-stage roll die forming (RDF) process is a plastic forming process that can manufacture a transmission part with a complex shape, such as a drum clutch, by using a die set with rotational rolls. However, it is difficult to satisfy dimensional accuracy because of spring-back and unfilling. The purpose of this study is to design a multi-stage RDF process for the manufacturing of a drum clutch to improve dimensional accuracy using an artificial neural network (ANN). Finite element (FE) simulation of the multi-stage RDF process is performed to predict the dimensional accuracy according to various clearances for each stage. Moreover, the ANN is used to determine the relationship between the clearance and dimensional accuracy of the drum clutch to reduce the number of FE simulation. The results of the FE simulation and ANN are used to determine the optimal clearance for each stage of the RDF process. Finally, the drum clutch is fabricated using the determined conditions. The experimental results are in good agreement with the results of FE simulation from the aspect of outer diameter, inner diameter, thickness of outer tooth, thickness of inner tooth, and face thickness of tooth.

9.
J Neurosurg Spine ; : 1-9, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32302980

RESUMO

OBJECTIVE: Maintaining lumbosacral (LS) arthrodesis and global sagittal balance after long fusion to the sacrum remains an important issue in the surgical treatment for adult spinal deformity (ASD). The importance and usefulness of LS fixation have been documented, but the optimal surgical long fusion to the sacrum remains a matter for debate. Therefore, the authors performed a retrospective study to evaluate fusion on CT scans and the risk factors for LS pseudarthrosis (nonunion) after long fusion to the sacrum in ASD. METHODS: The authors performed a retrospective study of 59 patients with lumbar degenerative kyphosis (mean age 69.6 years) who underwent surgical correction, including an interbody fusion of the L5-S1, with a minimum 2-year follow-up. Achievement of LS fusion was evaluated by analyzing 3D-CT scans at 3 months, 6 months, 9 months, 1 year, and 2 years after surgery. Patients were classified into a union group (n = 36) and nonunion group (n = 23). Risk factors for nonunion were analyzed, including patient and surgical factors. RESULTS: The overall fusion rate was 61% (36/59). Regarding radiological factors, optimal sagittal balance at the final follow-up significantly differed between two groups. There were no significant differences in terms of patient factors, and no significant differences with respect to the use of pedicle subtraction osteotomy, the number of fused segments, the proportion of anterior versus posterior interbody fusion, S2 alar iliac fixation versus conventional iliac fixation, or loosening of sacral or iliac screws. However, the proportion of metal cages to polyetheretherketone cages and the proportion of sacropelvic fixation were significantly higher in the union group (p = 0.022 and p < 0.05, respectively). CONCLUSIONS: LS junction fusion is crucial for global sagittal balance, and the use of iliac screws in addition to LS interbody fusion using a metal cage improves the outcomes of long fusion surgery for ASD patients.

10.
Materials (Basel) ; 12(14)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31330997

RESUMO

Mechanical properties, such as strength and stiffness, of laminated carbon fiber reinforced plastic (CFRP) are generally affected by the lay-up method. However, no precise design rules to replace steel products with CFRP have been established that satisfy these properties. Therefore, this study proposes a set of rules to design automotive parts with equivalent bending stiffness through structural analysis and genetic algorithms (GAs). First, the thickness of the CFRP product was determined by comparing the bending deformation of steel products by structural analysis. To minimize the orthotropic characteristics of CFRP, the quasi-isotropic lay-up method was implemented to determine the thickness. Next, the lay-up angle was determined using GAs. The optimized lay-up angle of the CFRP product with minimum bending deformation was determined by population generation, cross-over, mutation, and fitness evaluation. CFRP B-pillar reinforcement was fabricated using the determined conditions and the bending deformation of the single component was evaluated. Finally, the B-pillar assembled with CFRP reinforcement was investigated by the drop tower test.

11.
Taiwan J Obstet Gynecol ; 56(6): 801-805, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29241923

RESUMO

OBJECTIVE: To investigate the role of maternal serum placenta growth factor (PlGF) and quadruple test parameters in predicting the risk of small for gestational age (SGA) infants of mothers without preeclampsia. MATERIALS AND METHODS: We prospectively enrolled 300 pregnant patients who underwent blood sampling at 15-18 weeks gestation and followed them until delivery. Cases with SGA neonate delivery (n = 100) were compared with matched AGA neonate controls (n = 200). The plasma PlGF and quadruple markers were measured by enzyme-linked immunosorbent assay. The results were analyzed with Mann-Whitney U tests, and regression analysis was used to develop a model for the prediction of SGA. RESULTS: Women who delivered SGA neonates had decreased levels of PlGF (median 0.71 MoM versus 0.7 MoM; p < 0.01), hCG (median 0.97 MoM versus 1.06 MoM; p = 0.046) and uE3 (median 0.92 MoM versus 1.04 MoM) compared to the AGA group. AFP, hCG and inhibin-A levels did not differ significantly. A PlGF concentration <0.37 MoM had a sensitivity of 28.0% (95% CI: 19.5-37.9) and a specificity of 89.5% (95% CI: 84.4-93.4) for the prediction of SGA neonates without PE. CONCLUSION: SGA neonates in the absence of PE could potentially be identified at 15-18 weeks of pregnancy.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional/sangue , Testes para Triagem do Soro Materno/métodos , Fator de Crescimento Placentário/sangue , Segundo Trimestre da Gravidez/sangue , Adulto , Aneuploidia , Biomarcadores/sangue , Feminino , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez/genética , Estudos Prospectivos , Análise de Regressão , Sensibilidade e Especificidade , Estatísticas não Paramétricas
12.
IEEE Trans Image Process ; 15(7): 1751-62, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16830899

RESUMO

This paper proposes a mesh-based representation method for the disparity map of stereo images. The proposed method is designed to concentrate mainly on applications of view interpolation and stereo image compression. To obtain high image quality in the view interpolation and compression of stereo images, we formulate the view-interpolation error and prediction error. In the formulation, the view-interpolation and prediction errors depend not only on the accuracy of the disparity map, but also on the gradient of the stereo images. The proposed representation method for the disparity map is based on a triangular mesh structure, which minimizes the formulated interpolation and prediction errors. The experimental results show that the proposed method yields higher quality view-interpolated images and also has better performance in stereo image compression than the conventional methods.


Assuntos
Algoritmos , Compressão de Dados/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Fotogrametria/métodos , Técnica de Subtração , Gráficos por Computador , Análise Numérica Assistida por Computador , Processamento de Sinais Assistido por Computador
13.
J Agric Food Chem ; 52(10): 2832-9, 2004 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-15137822

RESUMO

As part of an effort to improve plant-derived foods such as potatoes, eggplants, and tomatoes, the antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells of a series of structurally related individual compounds were examined using a microculture tetrazolium (MTT) assay. The objective was to assess the roles of the carbohydrate side chain and aglycon part of Solanum glycosides in influencing inhibitory activities of these compounds. Evaluations were carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomatine, and their common aglycon tomatidine; the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine. All compounds were active in the assay, with the glycoalkaloids being the most active and the hydrolysis products less so. The effectiveness against the liver cells was greater than against the colon cells. Potencies of alpha-tomatine and alpha-chaconine at a concentration of 1 microg/mL against the liver carcinoma cells were higher than those observed with the anticancer drugs doxorubicin and camptothecin. Because alpha-chaconine, alpha-solanine, and alpha-tomatine also inhibited normal human liver HeLa (Chang) cells, safety considerations should guide the use of these compounds as preventative or therapeutic treatments against carcinomas.


Assuntos
Alcaloides/farmacologia , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias Hepáticas/patologia , Solanina/análogos & derivados , Solanum/química , Alcaloides/química , Humanos , Hidrólise , Solanum lycopersicum/química , Solanina/farmacologia , Relação Estrutura-Atividade , Tomatina/farmacologia , Células Tumorais Cultivadas
14.
Arch Pharm Res ; 26(6): 487-92, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12877560

RESUMO

This study investigated the effects of extremely low frequency magnetic fields (ELF-MFs) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. The mice were exposed to either a sham or 20 G ELF-MFs for 24 hours. Convulsants were then administered i.p. at various doses. The seizure induction time and duration were measured and lethal dose (LD50) and convulsant dose (CD50) of the clonic and tonic convulsion were calculated. The analysis of glutamate, glycine, taurine and GABA of mouse brain was accomplished by HPLC. The mice exposed to ELF-MFs showed moderately higher CD50, LD50 and onset time on the bicuculline-induced seizure. However, the ELF-MFs did not influence them in the NMDA and picrotoxin-induced seizures. After the exposure to MFs exposure, the glutamate level was increased and GABA was decreased significantly in NMDA and picrotoxin-induced seizure. The level of glutamate and GABA were not changed by MFs in bicuculline-induced seizure. These results suggest that ELF-MFs may alter the convulsion susceptibility through GABAergic mechanism with the involvement of the level of glutamate and GABA.


Assuntos
Convulsivantes/toxicidade , Campos Eletromagnéticos , Convulsões/induzido quimicamente , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Campos Eletromagnéticos/efeitos adversos , Camundongos , Camundongos Endogâmicos ICR , Convulsões/metabolismo
15.
Arch Pharm Res ; 26(3): 237-43, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12723938

RESUMO

We investigated the role of ascorbic acid on the redox status in streptozotocin-induced diabetic rats. In the plasma of diabetic rats, the ratio of reduced/total ascorbic acid was significantly decreased as compared with normal control. Ascorbic acid supplementation increased the reduced and total ascorbic acid contents as compared with diabetic control. In the rutin-treatment group, reduced and total contents of ascorbic acid were significantly decreased, however, the ratio of reduced/total contents of ascorbic acid had no difference as compared with diabetic rats. In the insulin-treatment group, this ratio is not significantly different as compared with diabetic control. However, in the insulin plus ascorbic acid treatment group, reduced form and the ratio of reduced/total ascorbic acid were significantly increased as compared with diabetic control. In addition, we measured the contents of malondialdehyde (MDA) in the plasma of diabetic rats. The contents of MDA was increased as compared with normal control, however, in insulin-treatment group, the contents of MDA was decreased as compared with diabetic rats. Ascorbic acid had no effects on the increases of MDA in diabetic rats. In conclusion, plasma ascorbic acid level and its reduced/total ratio reflects the status of the oxidative stress in the diabetic rats. Supplement of ascorbic acid did not correct the ratio of the reduced/ total ascorbic acid. However, supplement of insulin and ascorbic acid corrected the ratio of reduced/total ascorbic acid.


Assuntos
Ácido Ascórbico/sangue , Diabetes Mellitus Experimental/sangue , Malondialdeído/sangue , Animais , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley
16.
J Biol Chem ; 277(49): 47073-9, 2002 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-12359727

RESUMO

Nitric oxide (NO) regulates the biological activity of many enzymes and other functional proteins as well as gene expression. In this study, we tested whether pretreatment with NO regulates NO production in response to cytokines in cultured rat hepatocytes. Hepatocytes were recovered in fresh medium for 24 h following pretreatment with the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) and stimulated to express the inducible NO synthase (iNOS) with interleukin-1beta and interferon-gamma or transfected with the human iNOS gene. NO pretreatment resulted in a significant increase in NO production without changing iNOS expression for both conditions. This effect, which did not occur in macrophages and smooth muscle cells, was inhibited when NO was scavenged using red blood cells. Pretreatment with oxidized SNAP, 8-Br-cGMP, NO(2)(-), or NO(3)(-) did not increase the cytokine-induced NO production. SNAP pretreatment increased cytosolic iNOS activity measured only in the absence of exogenous tetrahydrobiopterin (BH(4)). SNAP pretreatment suppressed the level of GTP cyclohydrolase I (GTPCHI) feedback regulatory protein (GFRP) and increased GTPCHI activity without changing GTPCHI protein level. SNAP pretreatment also increased total cellular levels of biopterin and active iNOS dimer. These results suggest that SNAP pretreatment increased NO production from iNOS by elevating cellular BH(4) levels and promoting iNOS subunit dimerization through the suppression of GFRP levels and subsequent activation of GTPCHI.


Assuntos
Biopterinas/análogos & derivados , GMP Cíclico/análogos & derivados , Citocinas/metabolismo , GTP Cicloidrolase/metabolismo , Hepatócitos/metabolismo , Óxido Nítrico Sintase/química , Óxido Nítrico/farmacologia , Penicilamina/análogos & derivados , Animais , Biopterinas/farmacologia , Northern Blotting , Western Blotting , Células Cultivadas , GMP Cíclico/metabolismo , Dimerização , Relação Dose-Resposta a Droga , Ativação Enzimática , Humanos , Masculino , Músculo Liso/citologia , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Penicilamina/metabolismo , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Transfecção
17.
Mol Cells ; 13(2): 194-201, 2002 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-12018840

RESUMO

Caspases and c-Jun N-terminal kinase (JNK) are activated in tumor cells during induction of apoptosis. We investigated the signaling cascade and function of these enzymes in cisplatin-induced apoptosis. Treatment of Jurkat T-cells with cisplatin induced cell death with DNA fragmentation and activation of caspase and JNK. Bcl-2 overexpression suppressed activation of both enzymes, whereas p35 and CrmA inhibited only the DEVDase (caspase-3-like) activity, indicating that the activation of these enzymes may be differentially regulated. Cisplatin induced apoptosis with the cytochrome c release and caspase-3 activation in both wild-type and caspase-8-deficient JB-6 cells, while the Fas antibody induced these apoptotic events only in wild-type cells. This indicates that caspase-8 activation is required for Fas-mediated apoptosis, but not cisplatin-induced cell death. On the other hand, cisplatin induced the JNK activation in both the wild-type and JB-6 cells, and the caspase-3 inhibitor Z-DEVD-fmk did not inhibit this activation. The JNK overexpression resulted in a higher JNK activity, AP-1 DNA binding activity, and metallothionein expression than the empty vector-transfected cells following cisplatin treatment. It also partially protected the cells from cisplatin-induced apoptosis by decreasing DEVDase activity. These data suggest that the cisplatin-induced apoptotic signal is initiated by the caspase-8-independent cytochrome c release, and the JNK activation protects cells from cisplatin-induced apoptosis via the metallothionein expression.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Cisplatino/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Clorometilcetonas de Aminoácidos/metabolismo , Antineoplásicos/farmacologia , Apoptose/fisiologia , Inibidores de Caspase , Inibidores de Cisteína Proteinase/metabolismo , Fragmentação do DNA , Ativação Enzimática , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , Células Jurkat , Metalotioneína/genética , Metalotioneína/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serpinas/genética , Serpinas/metabolismo , Fator de Transcrição AP-1/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
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