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1.
Biomaterials ; 238: 119829, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058868

RESUMO

Magnesium (Mg)-based metals can be used as next-generation fracture internal fixation devices due to their specific properties. We used vascularized bone grafting fixed by degradable pure Mg screws and obtained satisfactory results in the treatment of osteonecrosis of the femoral head. However, the mechanical properties of these screws make them weaker than those made of traditional metals. In particular, one of the main challenges of using screws made of Mg-based metals is their application in fixation at important weight-bearing sites in the human body. Femoral neck fracture is a common clinical injury. In this injury, the large bearing stress at the junction requires a fixation device with extremely high mechanical strength. Surgery and appropriate internal fixation can accelerate the healing of femoral neck fractures. Traditional internal fixation devices have some disadvantages after surgery, including stress shielding effects and the need for secondary surgery to remove screws. On the basis of previous work, we developed high-strength pure Mg screws for femoral neck fractures. In this study, we describe the first use of high-purity Mg to prepare large-size weight-bearing screws for the fixation of femoral neck fractures in goats. We then performed a 48 weeks follow-up study using in vivo transformation experiments. The results show that these biodegradable high-purity Mg weight-bearing screws had sufficient mechanical strength and a degradation rate compatible with bone repair. Furthermore, good bone formation was achieved during the degradation process and reconstruction of the bone tissue and blood supply of the femoral head and femoral neck. This study provides a basis for future research on the clinical transformation of biodegradable high-purity Mg weight-bearing screws.

2.
Surg Technol Int ; 35: 406-409, 2019 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-31687779

RESUMO

Tantalum rod implantation with vascularized bone transplantation has been reported to be an effective method for the treatment of osteonecrosis of the femoral head (ONFH). However, long-term follow-up results were unclear. Sixty-five patients (71 hips) with ONFH treated with this technique were retrospectively reviewed. According to the Association Research Circulation Osseous (ARCO) classification, 21 hips were stage II, 30 were stage III, and 15 were stage IV. Sixty-one patients (66 hips) were followed for more than 10 years. Fifteen hips had to be converted to total hip arthroplasty (THA), the proportion of THA conversion surgery over 10 years postoperative was 4.76% for stage II, 16.7% for stage III, and 60% for stage IV, respectively. The 10-year joint-preserving success rate of the entire group was 77.2%. The Harris Hip Score (HHS) in the patients not receiving THA therapy increased from a mean of 51.35 points (ranged from 32 to 62 points) to 90.12 points (ranged from 72 to 99 points). The technique of tantalum rod implantation with vascularized bone grafting was an effective joint-preserving method for the treatment of ARCO stage II-III ONFH.


Assuntos
Transplante Ósseo , Necrose da Cabeça do Fêmur , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/cirurgia , Seguimentos , Humanos , Estudos Retrospectivos , Análise de Sobrevida , Tantálio , Resultado do Tratamento
3.
JBJS Essent Surg Tech ; 9(2): e20, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31579538

RESUMO

Background: The goal of a vascularized bone flap transfer is to replace the necrotic bone of the femoral head, restore the blood supply, and provide new bone and mechanical support for the femoral head. Description: The major steps of the procedure that are demonstrated in this article are: (1) using the anterolateral approach to the hip, the incision is made; (2) the interval between the rectus femoris and vastus lateralis is split, the transverse branch of the lateral femoral circumflex artery is identified, and the pedicle is isolated and protected; (3) the vascularized bone flap is harvested from the greater trochanter; (4) necrotic bone is debrided through a bone window made at the junction of the femoral neck and head; (5) the cancellous bone from the greater trochanter is implanted, and the vascularized bone flap is positioned and fixed; and (6) the wound is closed in layers. Complications are rare, and full weight-bearing is allowed after 3 months postoperatively. Alternatives: Free vascularized fibular graft. Rationale: Compared with a free vascularized fibular grafting technique, vascularized bone-grafting of the greater trochanter has the advantages of being less invasive, incurring lower donor-site morbidity, and not requiring any microsurgical technique because there is no vascular anastomosis.

4.
JBJS Essent Surg Tech ; 9(1): e5, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31086723

RESUMO

Background: Osteonecrosis of the femoral head often affects young active adults and leads to destruction of the hip joint and severe arthritis1-4. Despite improvements in hip arthroplasty design and techniques, it is unlikely that prosthetic replacements will endure for life. Alternatively, various head-preserving procedures have been used to avert or delay the need for a total hip arthroplasty5-11. Vascularized iliac bone flap transfer is a joint-preserving procedure that can be considered for younger patients with early or middle-stage osteonecrosis of the femoral head. Description: The major steps of the procedure include (1) an anterior approach to the affected hip, (2) creation of a bone flap from the iliac crest pedicled with the ascending branch of the lateral circumflex femoral artery, (3) obtaining cancellous bone from the iliac crest, (4) exposure of the anterior aspect of the femoral neck, (5) creation of a 2 × 2-cm window at the junction of the femoral head and neck, (6) debridement and removal of the necrotic bone, (7) implantation of the cancellous bone and vascularized bone flap, (8) fixation of the bone flap, and (9) layer-by-layer wound closure. Complications are rare, and full weight-bearing is allowed at 6 months postoperatively. Alternatives: Alternatives to the procedure include core decompression, nonvascularized bone-grafting, free vascularized fibular grafting, and vascularized greater trochanter grafting. Rationale: Various femoral head-preserving procedures have been reported. Core decompression is an effective femoral head-preserving procedure and is recommended as the first surgical treatment option for symptomatic small to medium-sized precollapse lesions. However, outcomes are poor when a patient has a large lesion or femoral head collapse. The advantage of vascularized iliac bone flap transfer is that it allows femoral head decompression, restores blood supply, and provides structural support. Thus, this procedure can be performed in patients with later osteonecrosis stages before hip osteoarthritis has progressed.

5.
J Arthroplasty ; 34(8): 1585-1592, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31031157

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) often affects young, active adults and leads to the destruction of the hip joint and disabling arthritis. Several procedures have been developed to prevent conversion to total hip arthroplasty (THA), especially in young patients who have a high rate of hip revision surgery. The aim of this long-term follow-up is to analyze the results of vascularized iliac bone flap transfer for ONFH treatment. METHODS: We retrospectively reviewed 856 patients (1006 hips) who accepted hip-preserving surgery with vascularized iliac bone grafting due to ONFH (Ficat and Arlet stages II-IV) from January 1985 to December 2012 at our hospital. Radiographic assessment was performed with the Ficat and Arlet system, clinical assessment was performed with the Harris Hip Score system, and quality of life was evaluated with the 36-Item Short Form Survey. The hips included 575 stage II hips, 382 stage III hips, and 49 stage IV hips. We defined clinical failure as conversion to THA or any other hip-preserving surgery because of hip symptoms. RESULTS: A total of 856 patients (1006 hips) were eventually followed up with an average time of 15 years (range 5-25). In total, 75 patients were lost to follow-up, and 105 hips were converted to THA. The average Harris Hip Score was 87.43 ± 6.42 points at the last follow-up, representing a great improvement compared to the 66.42 ± 6.52 points obtained preoperatively. The Kaplan-Meier survival analysis showed no difference in the 15-year survival rate between patients with stages II and III disease (using THA as an end point). However, the survival rate was lower for patients with stage IV disease than that for patients with stages II and III disease. The survival rate for patients in the glucocorticoid group was lower than that for patients in the idiopathic, alcoholic, and trauma groups. The Physical Component Summary scores ranged from 78 ± 10 to 85 ± 14 postoperatively compared to 30 ± 14 to 55 ± 15 preoperatively, and the postoperative Mental Component Summary scores (range from 34 ± 11 to 59 ± 12) were significantly higher than the preoperative scores (range from 72 ± 11 to 90 ± 10), representing great improvement in patient quality of life. Postoperative complications occurred in 86 patients (4.5%) during the follow-up, including 23 patients with deep venous thrombosis, 16 patients with meralgia paresthetica (which resolved), and 47 patients with secondary wound healing. CONCLUSION: The vascularized iliac bone flap grafting technique yields significant improvement (particularly in the precollapse disease stages in young patients) for restoration of the biomechanical support of the collapsed femoral head and reconstruction of the blood supply to the osteonecrotic area. This procedure allows these patients to avoid or delay the need for THA surgery.

6.
Stem Cell Res Ther ; 10(1): 72, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837004

RESUMO

BACKGROUND: The body is unable to repair and regenerate large area bone defects. Moreover, the repair capacity of articular cartilage is very limited. There has long been a lack of effective treatments for osteochondral lesions. The engineered tissue with biphase synthetic for osteochondral repair has become one of the hot research fields over the past few years. In this study, an integrated biomanufacturing platform was constructed with bone marrow mesenchymal stem cells (BMSCs)/porous tantalum (pTa) associated with chondrocytes/collagen membranes (CM) to repair large osteochondral defects in load-bearing areas of goats. METHODS: Twenty-four goats with a large osteochondral defect in the femoral heads of the left hind legs were randomly divided into three groups: eight were treated with chondrocytes/CM-BMSCs/pTa, eight were treated with pure CM-pTa composite, and the other eight goats were untreated. The repair effect was assessed by X-ray, gross observation, and histomorphology for 16 weeks after the operation. In addition, the biocompatibility of chondrocytes/CM-BMSCs/pTa was observed by flow cytometry, CCK8, immunocytochemistry, and Q-PCR. The characteristics of the chondrocytes/CM-BMSCs/pTa were evaluated using both scanning electron microscopy and mechanical testing machine. RESULTS: The integrated repair material consists of pTa, injectable fibrin sealant, and CM promoted adhesion and growth of BMSCs and chondrocytes. pTa played an important role in promoting the differentiation of BMSCs into osteoblasts. Three-dimensional CM maintained the phenotype of chondrocytes successfully and expressed chondrogenic genes highly. The in vivo study showed that after 16 weeks from implantation, osteochondral defects in almost half of the femoral heads had been successfully repaired by BMSC-loaded pTa associated with biomimetic 3D collagen-based scaffold. CONCLUSIONS: The chondrocytes/CM-BMSCs/pTa demonstrated significant therapeutic efficacy in goat models of large osteochondral defect. This provides a novel therapeutic strategy for large osteochondral lesions in load-bearing areas caused by severe injury, necrosis, infection, degeneration, and tumor resection with a high profile of safety, effectiveness, and simplicity.

7.
Mol Med Rep ; 19(5): 3505-3518, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896852

RESUMO

Transforming growth factor ß1 (TGF­ß1) has been suggested to be a candidate cytokine in the field of bone tissue engineering. Cytokines serve important roles in tissue engineering, particularly in the repair of bone damage; however, the underlying molecular mechanisms remain unclear. In the present study, the effects of TGF­ß1 on the osteogenesis and motility of hFOB1.19 human osteoblasts were demonstrated via the phenotype and gene expression of cells. Additionally, the role of the phosphatidylinositol 3­kinase/protein kinase B/mammalian target of rapamycin/S6 kinase 1 (PI3K/AKT/mTOR/S6K1) signalling pathway in the effects of TGF­ß1 on osteoblasts was investigated. It was demonstrated using Cell Counting Kit­8 and flow cytometry assays that the proliferation of human osteoblasts was promoted by 1 ng/ml TGF­ß1. In addition, alkaline phosphatase activity, Alizarin red staining, scratch­wound and Transwell assays were conducted. It was revealed that osteogenesis and the migration of cells were regulated by TGF­ß1 via the upregulation of osteogenic and migration­associated genes. Alterations in the expression of osteogenesis­ and migration­associated genes were evaluated following pre­treatment with a PI3K/AKT inhibitor (LY294002) and an mTOR/S6K1 inhibitor (rapamycin), with or without TGF­ß1. The results indicated that TGF­ß1 affected the osteogenesis and mineralisation of osteoblasts via the PI3K/AKT signalling pathway. Furthermore, TGF­ß1 exhibited effects on mTOR/S6K1 downstream of PI3K/AKT. The present study demonstrated that TGF­ß1 promoted the proliferation, differentiation and migration of human hFOB1.19 osteoblasts, and revealed that TGF­ß1 affected the biological activity of osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway. Our findings may provide novel insight to aid the development of bone tissue engineering methods for the treatment of bone injury.


Assuntos
Osteoblastos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Linhagem Celular , Movimento Celular , Proliferação de Células , Humanos , Modelos Biológicos , Osteogênese , Serina-Treonina Quinases TOR
8.
Mater Sci Eng C Mater Biol Appl ; 99: 1123-1132, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889646

RESUMO

Osteonecrosis of the femoral head (ONFH) results in collapse of the femoral head and rapid destruction of the hip joint. The repair of post-collapse articular cartilage and subchondral bone is challenging. We interrupted the blood supply to the femoral head and established a full-thickness articular defect animal model after ONFH was determined via X-ray. Porous tantalum and a Bio-Gide collagen membrane, co-cultured with bone marrow mesenchymal stem cells (BMSCs) in vitro, were implanted into the defect zone to repair the full-thickness articular defect. Hyaline cartilage was detected on top of the tantalum near the edge of the defect 12 weeks post-operatively. Porous tantalum and a Bio-Gide collagen membrane with BMSCs may repair full-thickness articular defects if the blood supply can be reconstructed in the post-collapse stage of ONFH.


Assuntos
Cartilagem Articular/patologia , Colágeno/farmacologia , Necrose da Cabeça do Fêmur/terapia , Membranas Artificiais , Células-Tronco Mesenquimais/citologia , Tantálio/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Técnicas de Cocultura , Necrose da Cabeça do Fêmur/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Osteogênese/efeitos dos fármacos , Fenótipo , Coelhos
9.
Orthopedics ; 42(2): e210-e215, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668885

RESUMO

The authors investigated changes in the blood supply of necrotic femoral heads using digital subtraction angiography (DSA). Digital subtraction angiography was used to evaluate the blood perfusion of osteonecrosis of the femoral head of 81 patients (81 hips). Necrotic hips were grouped according to the Association Research Circulation Osseous staging classification. Five parameters were assessed to evaluate the intraosseous blood supply of the necrotic femoral heads. The authors chose the most effective images retrospectively and measured the following parameters: the blood vessel diameter ratio between the medial circumflex femoral artery (MCFA) and the deep femoral artery (DFA) (MCFA/DFA); the blood vessel diameter ratio between the lateral circumflex femoral artery (LCFA) and the DFA (LCFA/DFA); the ratio between the MCFA extending length and the width of the femoral neck (A); the number of vessels that reach or exceed line I (a, horizontal line through the junction of the upper femoral head and neck); and the number of vessels that reach or exceed line II (b, the boundary between the femoral head and neck). Significantly negative correlation with Association Research Circulation Osseous stage II to IV necrosis was found for A, a, and b. These parameters were significant (P<.05). Compared with the length and distribution of the vessels, differences in width (MCFA/DFA and LCFA/DFA) were not statistically significant in patients with Association Research Circulation Osseous stage II to IV necrosis. The relative length of the MCFA and the number of vessels above line I and line II are related to the severity of osteonecrosis of the femoral head, as revealed by DSA. Evaluation of blood supply by DSA can be used as one element to predict the fate of precollapsed femoral head. [Orthopedics. 2019; 42(2):e210-e215.].


Assuntos
Angiografia Digital , Artéria Femoral/diagnóstico por imagem , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Int Orthop ; 43(5): 1083-1087, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29876626

RESUMO

OBJECTIVE: This study aims to investigate the early diagnosis and treatment of steroid-induced osteonecrosis of the femoral head. PATIENTS AND METHODS: From January 2010 to January 2014, a total of 350 patients, who required the use of large amounts of hormones, were enrolled into the study. These patients were followed up every three months after starting the hormone therapy. A total of 62 cases were screened, among which nine cases were asymptomatic. Furthermore, 38 patients were diagnosed as stage I and were given low-molecular weight heparin (LMWH) and vasodilator drugs. Moreover, 22 cases were diagnosed as stage IIa/b and underwent core decompression. In addition, two cases were diagnosed as stage IIc and underwent pedicled bone transplantation. During the follow-up period, ARCO staging was used for radiological evaluation, the HHS score was applied to evaluate for clinical efficacy, and SPSS 22.0 statistical software was used for the data analysis. RESULTS: A total of 60 patients were followed up for 24 months. Among these patients, 38 patients were diagnosed with ARCO stage I and underwent systematic therapy. No progress was found in 29 cases (76.3%). Furthermore, three cases progressed to stage IIb (7.8%), four cases progressed to stage IIc (10.5%), two cases progressed to stage III and IV, respectively (2.6%), and 16 cases (80%) did not progress after core decompression. In the 16 cases at stage IIa and four cases at stage IIb, and four cases (20%) progressed in stage III. The HHS score of stage I was 80.42 ± 3.25 before follow-up, while the HHS score was 86.46 ± 8.54 after follow-up, and the difference was statistically significant (P < 0.05). Furthermore, the HHS score of patients with stage IIa/b was 70.38 ± 4.62 before follow-up, while the HHS score was 80.28 ± 6.72 after follow-up, and the difference was statistically significant (P < 0.01). CONCLUSION: MRI remains as the most effective method for the non-invasive diagnosis of osteonecrosis, at present. Enhanced MRI may be able to detect early osteonecrosis, but further research is needed. Drug treatment and core decompression can achieve satisfactory results at the early stage.


Assuntos
Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/terapia , Cabeça do Fêmur/cirurgia , Adolescente , Adulto , Angiografia Digital , Anticoagulantes/administração & dosagem , Transplante Ósseo , Descompressão Cirúrgica , Diagnóstico Precoce , Feminino , Cabeça do Fêmur/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/classificação , Seguimentos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vasodilatadores , Adulto Jovem
11.
Medicine (Baltimore) ; 97(38): e12400, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30235709

RESUMO

The aim of this study was to investigate the relationship between femoroacetabular impingement (FAI) and superior retinacular artery interruption using plain radiographs and digital subtraction angiography (DSA).Sixty-one patients included in this study were divided into 2 groups based on the superior retinacular artery integrity as evaluated on DSA images. Group A included intact arteries: 33 patients (24 men, 9 women,); group B included interrupted arteries: 28 patients (21 men, 7 women). The parameters of abnormal radiographic findings thought to be associated with FAI, including positive crossover or figure-of-eight sign of acetabulum, lateral center edge angle (LCEA) >40°, Tönnis angle <0°, positive posterior wall sign, alpha angle >50°, and coxa profunda, were evaluated in all patients through plain radiographs.The cross-over sign (Group A: 0, Group B: 8, P = .0035), LCEA (Group A: 1, Group B: 7, P = .0190), Tönnis angle (Group A: 3, Group B: 13, P = .0026), and alpha angle (Group A: 7, Group B: 17, P = .0039) differed significantly between both groups. However, there were no statistically significant differences in posterior wall sign (Group A: 9, Group B: 12, P = .3143) or coxa profunda (Group A: 12, Group B: 8, P = .7096).Patients with interrupted blood supply of the superior retinacular arteries displayed more parameters of abnormal radiographic findings associated with FAI thereby indicating potential correlation between FAI and the interruption of superior retinacular arteries.


Assuntos
Angiografia Digital/métodos , Impacto Femoroacetabular/diagnóstico por imagem , Artéria Femoral/diagnóstico por imagem , Acetábulo/irrigação sanguínea , Acetábulo/diagnóstico por imagem , Adulto , Estudos Cross-Over , Feminino , Impacto Femoroacetabular/patologia , Artéria Femoral/patologia , Quadril/irrigação sanguínea , Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia/métodos , Estudos Retrospectivos , Adulto Jovem
12.
Int J Clin Pharmacol Ther ; 56(8): 387-392, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29882510

RESUMO

BACKGROUND: Tetramethylpyrazine, isolated from Ligusticum wallichii Franch., is widely used for the treatment of cerebrovascular and cardiovascular diseases in China. OBJECTIVE: To assess and compare the pharmacokinetic characteristics and bioequivalence of two tetramethylpyrazine phosphate (TMPP) tablets in healthy Chinese male subjects. MATERIALS AND METHODS: 20 healthy male subjects were randomly divided into two groups according to a two-period crossover design test. A single oral dose of 200 mg test or reference tablets was given with a 7-day washout period under fasting conditions. Blood samples were taken at scheduled time points, and the concentration of TMPP was measured by LC-MS. Drug And Statistical Software-Version 2.0 was used to calculate the pharmacokinetic parameters and assess bioequivalence of the two formulations. RESULTS: 20 subjects were enrolled in the study, and none dropped out. The main pharmacokinetic parameters of test and reference formulations were as follows: T1/2 was (1.79 ± 0.82) hours and (1.64 ± 0.52) hours, tmax was (0.76 ± 0.37) hours and (0.94 ± 0.44) hours, Cmax was (961.14 ± 309.64) ng/mL and (1,059.09 ± 350.69) ng/mL, AUC0-12h was (1,744.69 ± 643.49) ng×h/mL and (1,726.32 ± 494.11) ng×h/mL, AUC0-∞ was (1,756.95 ± 643.63) ng×h/mL and (1,740.16 ± 504.89) ng×h/mL, respectively. The relative bioavailability of TMPP tablets was 102.4 ± 26.0%, and no serious adverse events were reported. CONCLUSION: This single-dose study in healthy Chinese male fasted subjects showed that the TMPP test and reference tablets were bioequivalent.
.


Assuntos
Extratos Vegetais/farmacocinética , Pirazinas/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Disponibilidade Biológica , Estudos Cross-Over , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Comprimidos , Equivalência Terapêutica , Adulto Jovem
13.
Thorac Cancer ; 9(8): 950-955, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29917319

RESUMO

BACKGROUND: Malignant pleural effusion is a common complication of non-small cell lung cancer (NSCLC); however, treatment options remain limited. This study evaluated the safety and efficacy of sequential intrapleural therapy with lobaplatin and erythromycin for NSCLC-mediated malignant pleural effusion. METHODS: Fifty-six patients with NSCLC complicated with malignant pleural effusion were recruited for a prospective single-arm study from December 2014 to 2016; one patient dropped out. In addition to conventional systemic chemotherapy, lobaplatin and erythromycin were intrapleurally injected into subjects. Short and long-term responses were analyzed. The concentration of ultrafilterable platinum in the pleural effusion and plasma were detected at different time points. Incidences of severe adverse reactions were observed. RESULTS: In the 55 evaluable patients, the effective rate of pleural effusion was 81.8% after six weeks of treatment. Six and twelve months after treatment, the effective rates were 60% and 21.8%, respectively, and the one-year survival rate was 83.6%. The concentrations of lobaplatin in pleural effusion and plasma two hours after injecting 50 mg lobaplatin into the thoracic cavity were 13.763 ± 1.523 µg/mL and 1.120 ± 0.164 µg/mL, and 17 hours later were 1.961 ± 0.351 µg/mL and 0.578 ± 0.095 µg/mL, respectively. The rate of severe adverse reactions of the first cycle of systemic chemotherapy combined with lobaplatin and erythromycin did not significantly differ from the rate in the second cycle. CONCLUSION: Intrapleural combination therapy with lobaplatin and erythromycin is a safe and efficient treatment for patients with NSCLC-mediated malignant pleural effusion.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ciclobutanos/administração & dosagem , Eritromicina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Derrame Pleural Maligno/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Ciclobutanos/efeitos adversos , Eritromicina/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Biosci Trends ; 12(2): 201-207, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760359

RESUMO

An economical, rapid, and sensitive method of gas chromatography-mass spectrometry (GC-MS) was developed and validated to determine the presence of six pesticides (dichlorvos, acetochlor, atrazine, chlorpyrifos, α-endosulfan, and ß-endosulfan) in human plasma. The pesticides were extracted with acetonitrile and concentrated using anhydrous sodium sulfate. Then, the target compounds were analyzed and quantified with GC-MS using borneol as an internal standard. Separation was performed on a HP-5MS capillary column (30 m × 0.25 mm × 0.25 µm) with temperature programming. Detection was accomplished under electro-spray ionization (ESI) in selected ion monitoring (SIM) mode. Under optimized conditions, satisfactory linear ranges of 0.05-10 µg/mL were obtained for all of the analyzed pesticides. The linear correlation coefficients were greater than 0.99. The average recovery was between 86.8 and 106.5%. The inter- and intra-day precision ranged from 1.7-14.5% and 4.2-13.8%, respectively. Dichlorvos was unstable in plasma both at room temperature and when frozen. The other five pesticides were stable after storage at - 20°C for 17 days and two freeze-thaw cycles. Thirty-five plasma samples from 15 patients with acute self-poisoning were analyzed using this method. Dichlorvos was found in 13 plasma samples with a mean concentration of 0.289 µg/mL, and atrazine was found in 6 with a mean concentration of 0.261 µg/mL. Acetochlor was found in one plasma sample (0.153 µg/mL). This method is simple, reliable and cost-effective. It takes little time and does not waste solvents, and it can be used to routinely detect six pesticides in patients with acute poisoning.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Praguicidas/sangue , Envenenamento/sangue , Atrazina/sangue , Atrazina/envenenamento , Diclorvós/sangue , Diclorvós/toxicidade , Cromatografia Gasosa-Espectrometria de Massas/economia , Cromatografia Gasosa-Espectrometria de Massas/instrumentação , Humanos , Praguicidas/envenenamento , Envenenamento/diagnóstico , Espectrometria de Massas por Ionização por Electrospray/economia , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos
15.
Clin Lab ; 64(3): 277-285, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29739110

RESUMO

BACKGROUND: Therapeutic drug monitoring of vancomycin is very valuable due to the good correlation between trough levels and clinical outcome. Therefore, it is important to accurately determine the concentration of vancomycin in patient plasma for adequate dose-adjustment. The objective of this study was to develop a new liquid chromatography-mass spectrometry (LC-MS) method for determination of vancomycin in patient plasma and compare the results with those obtained from enzyme-multiplied immunoassay technique (EMIT). METHODS: After extraction by simple protein precipitation, vancomycin and bergenin (internal standard) were separated on a C18 column (150×4.6 mm, 5 µm) at 40°C by gradient elution with 0.1% formic acid and acetonitrile as the mobile phase and measured by electrospray ionization source in positive selective ion monitoring mode. Seventy-nine plasma samples from patients with severe infection were analyzed by enzyme-multiplied immunoassay technique and LC-MS method. MedCalc 15.2 software with Bland-Altman analysis and Passing-Bablok regression analysis was used for statistical analysis. RESULTS: The weighted (1/x2) calibration curve of the validated LC-MS was linear within the concentration range of 0.25 - 40 µg/mL. The inter- and intra-day precisions (%RSD) were less than 10.0%. No significant matrix effect was observed in the relevant time ranges. Comparison of the two methods indicated that results of the LC-MS were close to that of EMIT with a correlation coefficient of 0.957. Upon Bland-Altman analysis, the bias amounted to 2.9 µg/mL (95% confidence intervals of -3.4 - 9.2 µg/mL). CONCLUSIONS: The established LC-MS method and EMIT were both suitable for routine TDM of vancomycin.


Assuntos
Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Imunoensaio/métodos , Espectrometria de Massas/métodos , Vancomicina/sangue , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Humanos , /etnologia , Reprodutibilidade dos Testes , Vancomicina/farmacocinética , Vancomicina/uso terapêutico
16.
Int J Biol Macromol ; 116: 106-112, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29729342

RESUMO

The present study aimed to investigate the effects of a purified polysaccharide (SPS) from the safflower in a cellular model of steroid-associated necrosis of the femoral head (SANFH), which was established in primary murine osteoblasts suffering dexamethasone pretreatment. After treatment with SPS (25, 50 and 100 µg/ml), the degree of necrosis induced by dexamethasone was significantly reduced in osteoblasts as evidenced by an increase of cell viability and a decrease of apoptosis in osteoblasts. Furthermore, pretreatment with SPS (25, 50 and 100 µg/ml) significantly attenuated the activation of caspase-3 and cleavage of PARP relative to the model control cells. The addition of caspase-3 inhibitor (Z-DEVD-FMK) in dexamethasone-treated osteoblasts resulted in the inefficiency of SPS for inhibiting cellular apoptosis. Dose-dependent increases in alkaline phosphatase (ALP) activity, collagen synthesis and mineralization were also observed in SPS-treated osteoblasts at 72 h. The present study demonstrates that SPS may alleviate dexamethasone associated osteonecrosis by inhibiting caspsae-3-mediated apoptosis and may provide an alternative treatment for SANFH.


Assuntos
Apoptose/efeitos dos fármacos , Carthamus tinctorius/metabolismo , Caspase 3/metabolismo , Necrose da Cabeça do Fêmur/tratamento farmacológico , Polissacarídeos/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Camundongos , Osteoblastos/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Esteroides/farmacologia
17.
Orthop Surg ; 10(1): 69-74, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29424129

RESUMO

The present study investigates the feasibility of micro perfusion of femoral head specimens from femoral neck fracture patients by the inferior retinacular arteries and performing intraosseous artery quantitative analysis of the femoral head. Twelve femoral neck fracture patients who had undergone conventional hip replacement surgery were included in this study. Femoral head specimen arteries were first dissected and exposed and then perfused by the inferior retinacular arteries and all the femoral heads underwent micro-CT scanning. After micro-CT scanning, a digital 3-D model was reconstructed to quantify the femoral head intraosseous arteries for comparison with a normal femoral head. The artery length density, artery volume density, and artery length/volume ratio were calculated separately and compared with normal femoral head parameters. Micro-CT scanning displayed the epiphyseal arterial network structure and their fine vascular branches in all 12 femoral neck fractures. Blood was supplied from the inferior retinacular artery to the epiphyseal arterial network then to all the fine blood vessels within the femoral head. No statistical differences were observed in femoral heads' intraosseous artery length densities or volume densities between the normal and femoral neck fracture specimens, while the artery length/volume ratio showed a statistical difference, and the ratio increased from 19 to 46. Micro perfusion of the femoral head by the inferior retinacular arteries is possible and can present the epiphyseal network and their fine arterial branches in pathologic conditions to provide a morphological basis for the study of femoral head disease.


Assuntos
Fraturas do Colo Femoral/patologia , Cabeça do Fêmur/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias/diagnóstico por imagem , Artérias/patologia , Artroplastia de Quadril , Meios de Contraste , Estudos de Viabilidade , Feminino , Fraturas do Colo Femoral/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Humanos , Imagem Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Microtomografia por Raio-X
18.
Microsurgery ; 38(8): 882-888, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29214678

RESUMO

PURPOSE: We present the results of a study on the anatomy of the ascending branch of the lateral circumflex femoral artery (AB-LCFA) and the use of the pedicled iliac bone flap transfer perfused by AB-LCFA combined with external fixation for the treatment of the nonunion of upper femoral shaft fractures. METHODS: The orientation, diameter, length, and distribution of the AB-LCFA from 40 lower limbs of adult cadavers were dissected and measured. From 2000 to 2012, 13 patients with nonunion of upper femoral shaft fractures underwent pedicled iliac bone flap transfer perfused by the AB-LCFA combined with external fixation. The time of bone fracture union was recorded based on X-ray examination. The functional results of the femoral shaft were evaluated by the Klemm classification. RESULTS: The lateral circumflex femoral artery (LCFA) divided into ascending, transverse, and descending branches in 32 specimens (80%). The diameter of the AB-LCFA at the origin was 3.15 ± 0.9 mm and the length of the AB-LCFA was 8.51 ± 3.06 cm. The postoperative course of the procedure was uneventful in all 13 patients. The average follow-up was 15 months. Bone union was achieved in all patients and the average union time was 5.3 months. 12 patients achieved excellent or good functional results based on the Klemm classification. CONCLUSION: The AB-LCFA has a consistent orientation and abundant blood flow. The transfer of the iliac crest bone flap perfused by the AB-LCFA while combined with external fixation could be an option for treating the nonunion of upper femoral shaft fractures.


Assuntos
Fraturas do Fêmur/cirurgia , Fixação de Fratura/métodos , Fraturas não Consolidadas/cirurgia , Ílio/transplante , Retalhos Cirúrgicos , Adulto , Cadáver , Fixadores Externos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
Clin Pharmacol Drug Dev ; 7(3): 256-262, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28371488

RESUMO

This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t½ , 103.5 ± 18.8 and 105.8 ± 21.3 hours; Tmax , 0.7 ± 0.5 and 1.3 ± 0.8 hours; Cmax , 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC0∼360 , 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0 ng·mL-1 ·h; AUC0∼∞ , 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL-1 ·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin.


Assuntos
Anticoagulantes/sangue , Grupo com Ancestrais do Continente Asiático , Espectrometria de Massas em Tandem/normas , Varfarina/sangue , Adulto , Anticoagulantes/farmacologia , Grupo com Ancestrais do Continente Asiático/genética , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Masculino , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Equivalência Terapêutica , Varfarina/farmacologia
20.
Biomed Res Int ; 2017: 1624074, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201897

RESUMO

Steroid-associated osteonecrosis of the femoral head remains a challenging problem in orthopedics worldwide. One pathomechanism is ischemia of the femoral head, as a result of thrombus formation and vasoconstriction. The present study investigates the effects of combination prevention with enoxaparin and EGb 761 on steroid-associated ONFH in rabbits. Rabbits were randomly divided into 5 groups (control group, model group, enoxaparin group, ginkgo group, and combination group). With the exception of the control group, the groups of rabbits were modeled with lipopolysaccharide and methylprednisolone acetate. Starting with modeling, the enoxaparin group and ginkgo group were injected with 1 µg/kg/day enoxaparin subcutaneously and orally given 40 mg/kg/day EGb 761 for 4 weeks, respectively; the combination group received both treatments. After modeling for 6 weeks, the hematology data indicated prolonged PT and APTT in the three prevention groups. The micro-CT examination revealed higher bone density and better structure; histomorphometry revealed significant pathological changes. Immunohistochemistry revealed higher expression of BMP-2 and VEGF, thus revealing better osteogenesis and angiogenesis activities. Among the three prevention groups, the combination group had the most efficient results. In conclusion, the combined prevention with an anticoagulant and a vasodilator has the potential to decrease the incidence of steroid-associated ONFH in rabbits.


Assuntos
Anticoagulantes/administração & dosagem , Necrose da Cabeça do Fêmur/tratamento farmacológico , Osteonecrose/tratamento farmacológico , Vasodilatadores/administração & dosagem , Animais , Proteína Morfogenética Óssea 2/genética , Modelos Animais de Doenças , Enoxaparina/administração & dosagem , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/patologia , Ginkgo biloba/química , Humanos , Lipopolissacarídeos/administração & dosagem , Osteogênese/efeitos dos fármacos , Osteonecrose/induzido quimicamente , Osteonecrose/genética , Osteonecrose/patologia , Coelhos , Esteroides/efeitos adversos , Trombose/tratamento farmacológico , Trombose/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Vasoconstrição/efeitos dos fármacos
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