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1.
CA Cancer J Clin ; 73(1): 72-112, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35916666

RESUMO

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.


Assuntos
Carcinoma , Neoplasias do Seio Maxilar , Melanoma , Neoplasias Nasais , Seios Paranasais , Humanos , Carcinoma/diagnóstico , Neoplasias do Seio Maxilar/diagnóstico , Neoplasias do Seio Maxilar/patologia , Cavidade Nasal/patologia , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/epidemiologia , Neoplasias Nasais/terapia , Seios Paranasais/patologia
2.
BMC Surg ; 24(1): 125, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664803

RESUMO

BACKGROUND: The ideal treatment of terrble triad injuries and whether fixation of coronoid process fractures is needed or not are still debated. Therefore, we aimed to investigate if terrible triad injuries necessitate coronoid fracture fixation and evaluate if non-fixation treatments have similar efficacies and outcomes as fixation-treatments in cases of terrible triad injuries. METHODS: From August 2011 to July 2020, 23 patients with acute terrible triad injuries without involvement of the anteromedial facet of the coronoid process were included to evaluate the postoperative clinical and radiological outcomes (minimum follow-up of 20 months). According to the preoperative height loss evaluation of the coronoid process and an intraoperative elbow stability test, seven patients underwent coronoid fracture fixation, and the other eight patients were treated conservatively. The elbow range of motion (ROM), Mayo Elbow Performance Score (MEPS), and modified Broberg-Morrey score were evaluated at the last follow-up. In addition, plain radiographs were reviewed to evaluate joint congruency, fracture union, heterotopic ossification, and the development of arthritic changes. RESULTS: At the last follow-up, the mean arcs of flexion-extension and supination-pronation values were 118.2° and 146.8° in the fixation group and 122.5° and 151.3° in the non-fixation group, respectively. The mean MEPSs were 96.4 in the fixation group (excellent, nine cases; good, tow cases) and 96.7 in the non-fixation group (excellent, ten cases; good, two cases). The mean modified Broberg-Morrey scores were 94.0 in the fixation group (excellent, sevev cases; good, four cases) and 94.0 in the non-fixation group (excellent, ten cases; good, tow cases). No statistically significant differences in clinical scores and ROM were identified between the two groups. However, the non-fixation group showed a significantly lower height loss of the coronoid process than the fixation group (36.3% versus 54.5%). CONCLUSIONS: There were no significant differences in clinical outcomes between the fixation and non-fixation groups in terrible triad injuries.


Assuntos
Lesões no Cotovelo , Articulação do Cotovelo , Fixação Interna de Fraturas , Amplitude de Movimento Articular , Fraturas da Ulna , Humanos , Masculino , Adulto , Feminino , Fraturas da Ulna/cirurgia , Fraturas da Ulna/diagnóstico por imagem , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Amplitude de Movimento Articular/fisiologia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/fisiopatologia , Articulação do Cotovelo/cirurgia , Estudos Retrospectivos , Adulto Jovem , Resultado do Tratamento , Seguimentos
3.
Am J Hematol ; 98(6): 900-912, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36965007

RESUMO

There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina , Atividades Cotidianas , Estudos Retrospectivos , Temozolomida/uso terapêutico , Linfoma/terapia , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/patologia
4.
Endocr Pract ; 29(2): 141-147, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36252779

RESUMO

OBJECTIVE: To review the epidemiology, presentation, diagnosis, and management of head and neck paragangliomas. METHODS: A literature review of english language papers with focus on most current literature. RESULTS: Paragangliomas (PGLs) are a group of neuroendocrine tumors that arise in the parasympathetic or sympathetic ganglia. Head and neck PGLs (HNPGLs) comprise 65% to 70% of all PGLs and account for 0.6% of all head and neck cancers. The majority of HNPGLs are benign, and 6% to 19% of all HNPGLs develop metastasis outside the tumor site and significantly compromise survival. PGLs can have a familial etiology with germline sequence variations in different susceptibility genes, with the gene encoding succinate dehydrogenase being the most common sequence variation, or they can arise from somatic sequence variations or fusion genes. Workup includes biochemical testing to rule out secretory components, although it is rare in HNPGLs. In addition, imaging modalities, such as computed tomography and magnetic resonance imaging, help in monitoring in surgical planning. Functional imaging with DOTATATE-positron emission tomography, 18F-fluorodeoxyglucose, or 18F-fluorohydroxyphenylalanine may be necessary to rule out sites of metastases. The management of HNPGLs is complex depending on pathology, location, and aggressiveness of the tumor. Treatment ranges from observation to resection to systemic treatment. Similarly, the prognosis ranges from a normal life expectancy to a 5-year survival of 11.8% in patients with distant metastasis. CONCLUSION: Our review is a comprehensive summary of the incidence, mortality, pathogenesis, presentation, workup and management of HNPGLs.


Assuntos
Neoplasias de Cabeça e Pescoço , Paraganglioma Extrassuprarrenal , Humanos , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Paraganglioma/diagnóstico , Paraganglioma/epidemiologia , Paraganglioma/genética , Paraganglioma/terapia , Paraganglioma Extrassuprarrenal/diagnóstico , Paraganglioma Extrassuprarrenal/epidemiologia , Paraganglioma Extrassuprarrenal/genética , Paraganglioma Extrassuprarrenal/terapia , Succinato Desidrogenase/genética , Tomografia Computadorizada por Raios X
5.
J Korean Med Sci ; 38(16): e128, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37096311

RESUMO

BACKGROUND: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. METHODS: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. RESULTS: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. CONCLUSION: Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.


Assuntos
Pré-Eclâmpsia , Trofoblastos , Recém-Nascido , Gravidez , Humanos , Feminino , Trofoblastos/metabolismo , Placenta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Leucócitos Mononucleares/metabolismo , Nucleosídeo Difosfato Quinase D/metabolismo
6.
BMC Surg ; 23(1): 193, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37407984

RESUMO

BACKGROUND: Anatomical total shoulder arthroplasty (aTSA) has been used to manage degenerative diseases such as primary osteoarthritis. An increase in the use of this procedure has led to several developments in humeral and glenoid components to improve patient outcomes. This study aimed to compare clinical and radiological outcomes of the newly-introduced convertible metal-backed glenoid components with cemented polyethylene glenoid components in aTSA, and to determine whether the new component would be comparable to a conventional one for reducing the burden of future revision or conversion surgeries. METHODS: Medical records of fifty patients who underwent aTSA with at least two years of follow-up were retrospectively reviewed. Eighteen patients received convertible metal-backed glenoid components with vitamin E1-coated liner (MB group), while thirty-two patients received conventional cemented polyethylene glenoid components (PE group). Pre- and postoperative clinical and radiological outcomes (acromion-greater tuberosity angle [AGA] and humeral lateral offset [LO]) at final follow-up were assessed. Radiolucent lines (RLLs) and loosening around the humeral and glenoid components were also evaluated. RESULTS: Clinical outcomes improved after surgery in both groups (all p < 0.001). The arc of rotation measured by AGA improved postoperatively in both groups (all p < 0.001), and AGA and LO were not different according to the type of glenoid components (all p > 0.05). Overall complication rates including RLLs of PE and MB groups were 43.8% (14/32) and 16.7% (3/18), respectively (p = 0.031). Although the PE group had more RLLs than did the MB group (p < 0.05), related symptoms and/or glenoid implant loosening were not observed in both groups. Subscapularis failure occurred in two patients in the PE group and in one in the MB group. CONCLUSION: The convertible metal-backed glenoid implant with vitamin E1-coated liner may be a good alternative for considering the potential for an easier conversion to reverse total shoulder arthroplasty.


Assuntos
Artroplastia do Ombro , Prótese Articular , Osteoartrite , Articulação do Ombro , Humanos , Polietileno , Articulação do Ombro/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Osteoartrite/cirurgia , Desenho de Prótese , Seguimentos
7.
BMC Musculoskelet Disord ; 23(1): 42, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012506

RESUMO

BACKGROUND: Surgical fixation using hook plates is widely used in the treatment of acromioclavicular (AC) joint dislocations. The purpose of this study was to evaluate the incidence and shape of subacromial erosions after removal of the hook plate in type 5 AC joint dislocations. Further, we evaluated the effect of the shape of the subacromial erosion on the rotator cuff. METHODS: We retrospectively reviewed 30 patients who underwent hook plate fixation for type 5 AC joint dislocations at our hospital between December 2010 and December 2018. Patients with a follow-up of at least 1 year were included. Clinical outcomes were assessed using the final follow-up Constant-Murley, Korean Shoulder, and visual analog scores. To ensure that the appropriate reduction was well maintained, the coracoclavicular distances of the injured and contralateral sides were evaluated at the last follow-up. Computed tomography was performed to investigate the presence and shape of the subacromial erosion after hook plate removal at 4 months after surgery. Ultrasonography was performed to investigate the presence of rotator cuff lesions at the last follow-up. Clinical and radiological outcomes were compared between groups divided according to the presence and types of subacromial erosions. RESULTS: Subacromial erosion was observed in 60% of patients (18/30): 13, 2, and 3 simple groove, cave, and marginal protrusion types, respectively. Four patients showed reduction loss at the final follow-up. There were no significant differences in clinical and radiological outcomes between the groups with and without subacromial erosion. Moreover, there were no significant differences between groups according to the types of subacromial erosion. There were no rotator cuff lesions, such as partial tears, in the injured shoulders. CONCLUSIONS: Hook plate fixation may induce subacromial erosions. However, the subacromial erosions caused by the hook plate did not affect the clinical outcomes of type 5 AC joint dislocations. Moreover, regardless of its shape, the subacromial erosion did not affect the clinical outcomes nor cause rotator cuff lesions after plate removal.


Assuntos
Articulação Acromioclavicular , Luxações Articulares , Placas Ósseas , Clavícula , Humanos , Estudos Retrospectivos , Manguito Rotador , Resultado do Tratamento
8.
Acta Orthop Belg ; 88(4): 739-747, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36800658

RESUMO

Although various surgical techniques have been reported for the treatment of advanced Kienböck's disease (Lichtman stage IIIB and above), the ap- propriate operative treatment is still being debated. This study compared the clinical and radiological outcomes of combined radial wedge and shortening osteotomy (CRWSO) and scaphocapitate arthrodesis (SCA) in the treatment of advanced Kienböck's disease (above type IIIB) with a minimum of 3 years of follow-up. We analyzed the data from 16 and 13 patients who underwent CRWSO and SCA, respectively. The average follow-up period was 48.6±12.8 months. Clinical outcomes were evaluated using the flexion-extension arc, grip strength, Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH), and Visual Analogue Scale (VAS) for pain. The following radiological parameters were measured: ulnar variance (UV), carpal height ratio (CHR), radioscaphoid angle (RSA), and Stahl index (SI). Osteoarthritic changes in the radiocarpal and midcarpal joints were evaluated using computed tomography (CT). Clinically, both groups showed significant improvements in the grip strength, DASH, and VAS at final follow-up. However, regarding the flexion-extension arc, the CRWSO group showed a significant improvement, while the SCA group did not. Radiologically, compared to the preoperative values, the CHR results improved at final follow-up in the CRWSO and SCA groups. There was no statistically significant difference in the degree of CHR correction between the 2 groups. By the final follow-up visit, none of the patients in either group had progressed from Lichtman stage IIIB to stage IV. Considering restoration of wrist joint range of motion, CRWSO may be a good alternative for limited carpal arthrodesis for advanced Kienböck's disease.


Assuntos
Ossos do Carpo , Osteonecrose , Humanos , Ossos do Carpo/cirurgia , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/cirurgia , Osteotomia/métodos , Artrodese/métodos , Amplitude de Movimento Articular , Osteonecrose/diagnóstico por imagem , Osteonecrose/cirurgia , Força da Mão , Seguimentos
9.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200910

RESUMO

To increase the half-life of growth hormones, we proposed its long-lasting regulation through the ubiquitin-proteasome system (UPS). We identified lysine residues (K67, K141, and K166) that are involved in the ubiquitination of human growth hormone (hGH) using ubiquitination site prediction programs to validate the ubiquitination sites, and then substituted these lysine residues with arginine residues. We identified the most effective substituent (K141R) to prevent ubiquitination and named it AUT-hGH. hGH was expressed and purified in the form of hGH-His, and ubiquitination was first verified at sites containing K141 in the blood stream. Through the study, we propose that AUT-hGH with an increased half-life could be used as a long-lasting hGH in the blood stream.


Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Ubiquitinação , Animais , Citoplasma/metabolismo , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/patologia , Células HEK293 , Meia-Vida , Humanos , Masculino , Camundongos , Células NIH 3T3 , Ratos , Ratos Sprague-Dawley
10.
Cancer ; 126(19): 4270-4272, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32644193

RESUMO

The US Food and Drug Administration granted acalabrutinib approval as the second Bruton tyrosine kinase (BTK) inhibitor to treat patients with chronic lymphocytic leukemia and small lymphocytic lymphoma as monotherapy or in combination with obinutuzumab. This approval was based on 2 phase 3 trials: ELEVATE-TN and ASCEND. There are several concerns with the design of these trials, including suboptimal treatment of patients in the control arm, expansion of the trial population, and lack of data regarding efficacy or tolerability compared with ibrutinib, a first-in-class drug. The Food and Drug Administration approval of acalabrutinib for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma represents concerning drug approval patterns in the United States and a weakness in evidence generation.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Humanos , Estados Unidos , United States Food and Drug Administration
12.
Int Orthop ; 43(6): 1421-1427, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30617613

RESUMO

BACKGROUND: Total elbow arthroplasty (TEA) is considered a successful treatment for several conditions, including rheumatoid arthritis and comminuted fractures. However, failure rates as high as 62% have been reported, with many patients requiring surgical revision. Causes of failure requiring revision can be classified as infected or non-infected. This study evaluated the clinical and radiologic outcomes of TEA revision surgery according to causes of failure. METHODS: Twenty patients undergoing revision TEAs in 2010-2015 were retrospectively evaluated. Mean follow-up was 52.7 months. Patients were categorized into infected and non-infected groups based on radiologic and serologic tests. Clinical outcomes included range of motion (ROM) and Mayo Elbow Performance Score (MEPS), and radiological outcomes included loosening signs on anteroposterior (AP) and lateral plain radiographs at final follow-up. Complications were assessed in both groups. RESULTS: Overall, mean MEPS was 79.7, and mean ROM arc was 97.9° at final follow-up. Nine patients underwent revision due to infection, and 11 due to non-infectious causes. Mean MEPS in these two groups was 75.6 and 83.5, respectively, and mean ROM arc for flexion-extension was 89.4° and 108°, respectively. Two (22%) of the nine patients in the infection group required second revision surgery due to recurrent infection. No patient in the non-infected group underwent second revision surgery. The most frequent complication in the infected group was osteolysis, observed in five patients, including four with symptomatic aseptic loosening and one with non-symptomatic osteolysis. Two patients in the non-infected group demonstrated a non-progressive radiolucent line, which was asymptomatic at final follow-up. CONCLUSION: Revision TEA provided clinical improvement in elbow function and resulted in satisfactory outcomes. Outcomes were worse in the infected than in the non-infected groups. Comorbidities and older age were apparent risk factors for infected TEA.


Assuntos
Artroplastia de Substituição do Cotovelo , Articulação do Cotovelo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição do Cotovelo/efeitos adversos , Articulação do Cotovelo/diagnóstico por imagem , Prótese de Cotovelo/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Radiografia , Amplitude de Movimento Articular , Reoperação/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
Foot Ankle Surg ; 25(4): 434-440, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30321971

RESUMO

BACKGROUND: The purpose of this study was to compare the clinical and radiographic outcomes between feet with or without postoperative sesamoid reduction of proximal metatarsal chevron osteotomy for moderate to severe hallux valgus deformity. METHODS: All of 110 feet were allocated into two groups (reduction group; 66 feet, non-reduction group; 44 feet) according to the reduction status of sesamoid at 6 months after surgery. The clinical and radiographic results of the two groups were compared preoperatively, 6 months follow-up, and at last follow-up. RESULTS: The overall improvement in clinical outcomes was similar in both groups at average 4-year follow-up. However, the radiographic outcomes and recurrence rate were significantly worse in the sesamoid non-reduction group. CONCLUSIONS: Our results suggested that postoperative incomplete reduction of sesamoid may increase a risk for the recurrence of hallux valgus deformity.


Assuntos
Hallux Valgus/cirurgia , Hallux/cirurgia , Ossos Sesamoides/cirurgia , Adulto , Idoso , Feminino , Hallux/diagnóstico por imagem , Hallux Valgus/diagnóstico por imagem , Humanos , Masculino , Ossos do Metatarso/cirurgia , Pessoa de Meia-Idade , Osteotomia/métodos , Cuidados Pós-Operatórios , Radiografia , Recidiva , Estudos Retrospectivos , Ossos Sesamoides/diagnóstico por imagem , Resultado do Tratamento
15.
J Nanosci Nanotechnol ; 18(2): 1303-1307, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448578

RESUMO

Customized titanium (Ti) meshes were treated with O2 plasma and acrylic acid plasmapolymerization (PPAAc). The optimum conditions for PPAAc were as follows: 20 W, 15 mTorr, and 5 min. Hydroxyapatite formation increased in Ti meshes treated with O2 and PPAAc compared with that in untreated Ti meshes. Moreover, MC3T3-E1 cells exhibited improved cell spreading, attachment, proliferation in PPAAc treated Ti mesh than in untreated Ti mesh. This result revealed that O2 and PPAAc surface treatment on Ti mesh was potential tool for improving the bone formation on the Ti mesh clinically application.

16.
Mol Ther ; 24(9): 1538-49, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27455881

RESUMO

Recovery from ischemic tissue injury can be promoted by cell proliferation and neovascularization. Transient expression of four pluripotency factors (Pou5f1, Sox2, Myc, and Klf4) has been used to convert cell types but never been tested as a means to promote functional recovery from ischemic injury. Here we aimed to determine whether transient in situ pluripotency factor expression can improve neurobehavioral function. Cerebral ischemia was induced by transient bilateral common carotid artery occlusion, after which the four pluripotency factors were expressed through either doxycycline administration into the lateral ventricle in transgenic mice in which the four factors are expressed in a doxycycline-inducible manner. Histologic evaluation showed that this transient expression induced the proliferative generation of astrocytes and/or neural progenitors, but not neurons or glial scar, and increased neovascularization with upregulation of angiogenic factors. Furthermore, in vivo pluripotency factor expression caused neuroprotective effects such as increased numbers of mature neurons and levels of synaptic markers in the striatum. Dysplasia or tumor development was not observed. Importantly, neurobehavioral evaluations such as rotarod and ladder walking tests showed that the expression of the four factors dramatically promoted functional restoration from ischemic injury. These results provide a basis for novel therapeutic modality development for cerebral ischemia.


Assuntos
Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatologia , Expressão Gênica , Recuperação de Função Fisiológica/genética , Animais , Astrócitos/metabolismo , Contagem de Células , Linhagem Celular , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modelos Animais de Doenças , Genes myc , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Ventrículos Laterais/metabolismo , Ventrículos Laterais/patologia , Camundongos , Camundongos Transgênicos , Neovascularização Patológica/genética , Células-Tronco Neurais/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição SOXB1/genética
17.
J Hand Surg Am ; 42(4): 292.e1-292.e8, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28249791

RESUMO

PURPOSE: This study attempted to evaluate a series of patients with hereditary multiple exostoses (HME) who could not be categorized according to the widely accepted Masada classification and to identify radiographic variables such as radial bowing, ulnar shortening, ulnar variance, radial articular angle, and carpal slip predictive of deformity. METHODS: We retrospectively reviewed data on 102 upper limbs of 53 pediatric patients with HME. Demographics, site of forearm involvement, and radiographic parameters were documented. Patients with exostoses of the forearms were categorized into 6 groups based on location of the exostoses and presence or absence of a dislocated radial head. Proportional ulnar shortening was calculated as the ratio of ulnar length to radial length. RESULTS: According to the Masada classification, 4 limbs were normal, 10 were type I, 2 were type II, and 24 were type III. Sixty-six limbs were unclassifiable. We classified those 66 limbs using a modification of the Masada classification. Of the 106 limbs, 11 (10.3%) had a dislocated radial head. Based on the radiographic analysis, patients with proportional ulnar shortening of less than 0.9 had a higher risk of radial head dislocation than did those with proportional ulnar shortening of 0.9 or greater. Patients with radial bowing greater than 8.1% showed a higher frequency of radial head dislocation than did those with radial bowing of 8.1% or less. Exostoses of both the distal radius and ulna tended to increase the rate of radial head dislocation. A greater amount of negative ulnar variance caused more radial bowing and a greater radioarticular angle. CONCLUSIONS: We propose a new comprehensive forearm classification for patients with HME. Proportional ulnar shortening less than 0.9 and radial bowing 8.1% or greater can be used to predict the risk of radial head dislocation. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.


Assuntos
Exostose Múltipla Hereditária/diagnóstico por imagem , Antebraço/anormalidades , Luxações Articulares/diagnóstico por imagem , Rádio (Anatomia)/diagnóstico por imagem , Deformidades Congênitas das Extremidades Superiores/classificação , Deformidades Congênitas das Extremidades Superiores/diagnóstico por imagem , Adolescente , Adulto , Criança , Pré-Escolar , Exostose Múltipla Hereditária/complicações , Feminino , Antebraço/diagnóstico por imagem , Humanos , Masculino , Rádio (Anatomia)/anormalidades , Estudos Retrospectivos , Ulna/anormalidades , Ulna/diagnóstico por imagem , Articulação do Punho/diagnóstico por imagem , Adulto Jovem
18.
J Virol ; 88(16): 9233-44, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24899196

RESUMO

UNLABELLED: Diacylglycerol acyltransferase-1 (DGAT1) is involved in the assembly of hepatitis C virus (HCV) by facilitating the trafficking of the HCV core protein to the lipid droplet. Here, we abrogated DGAT1 expression in Huh-7.5 cells by using either the transcription activator-like effector nuclease (TALEN) or lentivirus vector short hairpin RNA (shRNA) and achieved complete long-term silencing of DGAT1. HCV entry was severely impaired in DGAT1-silenced Huh-7.5 cell lines, which showed markedly diminished claudin-1 (CLDN1) expression. In DGAT1-silenced cell lines, the forced expression of CLDN1 restored HCV entry, implying that the downregulation of CLDN1 is a critical factor underlying defective HCV entry. The expression of the gene coding for hepatocyte nuclear factor 4α (HNF4α) and other hepatocyte-specific genes was also reduced in DGAT1-silenced cell lines. After DGAT1 gene rescue, CLDN1 expression was preserved, and HCV entry was restored. Strikingly, after DGAT1 silencing, CLDN1 expression and HCV entry were also restored by low-dose palmitic acid treatment, indicating that the downregulation of CLDN1 was associated with altered fatty acid homeostasis in the absence of DGAT1. Our findings provide novel insight into the role of DGAT1 in the life cycle of HCV. IMPORTANCE: In this study, we report the novel effect of complete silencing of DGAT1 on the entry of HCV. DGAT1 was recently reported as a host factor of HCV, involved in the assembly of HCV by facilitating the trafficking of the HCV core protein to lipid droplets. We achieved complete and long-term silencing of DGAT1 by either TALEN or repeated transduction of lentivirus shRNA. We found that HCV entry was severely impaired in DGAT1-silenced cell lines. The impairment of HCV entry was caused by CLDN1 downregulation, and the expression of HNF4α and other hepatocyte-specific genes was also downregulated in DGAT1-silenced cell lines. Our results suggest new roles of DGAT1 in human liver-derived cells: maintaining intracellular lipid homeostasis and affecting HCV entry by modulating CLDN1 expression.


Assuntos
Claudina-1/genética , Diacilglicerol O-Aciltransferase/genética , Regulação para Baixo/genética , Hepacivirus/genética , Hepacivirus/patogenicidade , Linhagem Celular Tumoral , Fator 4 Nuclear de Hepatócito/genética , Hepatócitos/virologia , Humanos , Internalização do Vírus
19.
Bioorg Med Chem Lett ; 25(1): 38-42, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25433999

RESUMO

Although collagen pentapeptide (Lys-Thr-Thr-Lys-Ser, KTTKS) has received a great deal of attention owing to its collagen biosynthesis-stimulating effects, its enzymatic instability in the skin is an obstacle to effective topical application. PEGylation is a useful approach for improving the chemical and biological stability of peptides. However, the polydispersity of poly(ethylene glycol) (PEG) produces conjugates with different molecular sizes, which may create difficulties in chemical characterization and purity control, and in variability of biological properties. To overcome these difficulties, monodisperse PEG was site-specifically conjugated to the N-terminal amine of KTTKS to produce a single molecular conjugate, enabling more complete chemical characterization and more exact product specifications. PEG-KTTKS conjugates prepared using monodisperse PEG with two different molecular weights, monodisperse PEG220 and PEG572, were characterized by mass spectrometry. These monodisperse PEG-KTTKS conjugates showed no cytotoxicity (1-100 µM) and stimulated collagen biosynthesis in human skin fibroblasts. They also had high stability against proteolytic enzymes in rat skin. This study demonstrates the usefulness of monodisperse PEG for preparing chemically defined conjugates and suggests that monodisperse PEG-KTTKS would be a good candidate for use as a collagen biosynthesis-stimulating agent.


Assuntos
Colágeno/biossíntese , Colágeno/síntese química , Oligopeptídeos/síntese química , Polietilenoglicóis/síntese química , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Colágeno/farmacologia , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Oligopeptídeos/farmacologia , Polietilenoglicóis/farmacologia , Ratos
20.
J Clin Med ; 13(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673473

RESUMO

Treatment of a comminuted proximal humerus fracture (PHF) in elderly patients with severe osteoporosis is challenging, often leading to arthroplasty (such as hemiarthroplasty or reverse shoulder arthroplasty) as the treatment of choice. However, arthroplasty does not always guarantee favorable outcomes. In contrast, the use of intramedullary fibular strut allografts provides additional reduction stability during locking plate fixation; however, to our knowledge, there is limited literature on the use of fibular strut allografts, including the fibular head. Here we aim to report the advantages of using a fibular strut containing the fibular head in severe osteoporotic PHFs. We present the case of an 88-year-old female patient with severe osteoporosis diagnosed with a left PHF accompanied by severe metaphyseal comminution following a fall from a chair. Rather than shoulder arthroplasty, we performed osteosynthesis using a fibular strut allograft containing the fibular head. At the one-year follow-up after surgery, we observed excellent bony union and a favorable functional outcome without major complications, such as reduction loss. The novel use of a fibular strut allograft containing the fibular head could be promising for PHFs with severe metaphyseal comminution, potentially avoiding the need for arthroplasty.

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