Downregulating STAT1/caspase‐3 signaling with fludarabine to alleviate progression in a rat model of steroid‐induced avascular necrosis of the femoral head

2018 ◽  
Vol 33 (4) ◽  
pp. e22265 ◽  
Author(s):  
Jian Lin ◽  
Weihui Qi ◽  
Kai Chen ◽  
Yingzhao Yan ◽  
Xiaobin Li ◽  
...  
2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Heng-feng Yuan ◽  
Jian-feng Pan ◽  
Shuo Li ◽  
Chang-an Guo ◽  
Shu-hao Liu ◽  
...  

This research was designed to investigate the protective effects of TSPN on steroid-induced avascular necrosis of the femoral head (ANFH) and the likely mechanisms of those effects. As an in vivo study, TSPN was shown to be protective against steroid-induced ANFH due to the upregulation of VEGF-A. Furthermore, TSPN attenuated the apoptosis of osteocytes and reduced the expression of Caspase-3 relative to the model group. As an in vitro study, TSPN exerted a concentration-dependent protective effect against apoptosis in MC3T3-E1 cells. Moreover, TSPN (at a dose of 100 μg/mL) significantly reversed the dexamethasone-induced augmentation of Caspase-3 expression and activity. Therefore, our study demonstrated that TSPN had a protective effect against steroid-induced ANFH that was related to the upregulation of VEGF-A and the inhibition of apoptosis and Caspase-3 activation.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jie Han ◽  
Yuan Chai ◽  
Xiao-yun Zhang ◽  
Feng Chen ◽  
Zhi-wei Xu ◽  
...  

Background. Clinically, the traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). The present study aimed to investigate the mechanisms underlying the therapeutic effect of Gujiansan. Methods. A rat model of SANFH was established by the injection of dexamethasone (DEX) at a high dosage of 25 mg/kg/d. Then, Gujiansan was intragastrically administered for 2 weeks, 4 weeks, and 8 weeks, and histological examination of the femoral head was performed. The expression levels of related mRNAs and proteins were analyzed by qRT-PCR, Western blotting, and immunohistochemistry, and the levels of bone biochemical markers and cytokines were detected with ELISA kits. Results. Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and time-dependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. In addition, Gujiansan increased the levels of bone formation- and bone resorption-specific markers (osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase-5b (TRACP-5b), N-terminal telopeptides of type I collagen (NTX-1), and C-terminal telopeptide of type I collagen (CTX-1)) and decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and CRP) in a dose- and time-dependent manner. Conclusions. Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ultimately ameliorates SANFH.


1999 ◽  
Vol 41 (2) ◽  
pp. 381
Author(s):  
Hae Woong Jeong ◽  
Jeong Hee Yoon ◽  
Chang Soo Kim

2020 ◽  
Vol 63 (2) ◽  
pp. 18-23
Author(s):  
Alejandro Jardón Gómez ◽  
Ana Cristina King ◽  
Carlos Pacheco Díaz

The clinical presentation of a proximal femoral fracture is completely different between young and adult patients. Unlike closed proximal femoral fractures, the incidence of exposed fractures is found in the young population between 15 and 30 years of age. Osteonecrosis of the femoral head is one the complications we can find in this type of fractures. Avascular necrosis (AVN or osteonecrosis) is defined as the interruption of blood supply to the femoral head due to trauma, infectionalcohol or steroid use, resulting in bone necrosis, joint collapse and osteoarthrosis. The treatment will depend on the clinical presentation, age of the patient and when the diagnosis is made. This is a case report of a 16-year-old patient with a gunshot wound on the hip. Surgical cleansing and closed reduction plus internal fixation with a nail in the center of the spine were performed. A 3-year clinical and radiographic follow up was made, observing the evolution of the fracture and the subsequent avascular necrosis that the patient presented. Key words: Proximal femoral fracture; hip; avascular necrosis (AVN, osteonecrosis); open fracture; osteoarthritis.


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Catarina Borges Cardoso ◽  
Sheila Canevese Rahal ◽  
Maria Jaqueline Mamprim ◽  
Hugo Salvador Oliveira ◽  
Alessandra Melchert ◽  
...  

Background: The avascular necrosis of the femoral head is a development disease caused by ischemic necrosis, which is mainly observed in young dogs. The etiology of the disease remains controversial. The diagnosis requires imaging exams such as MRI and radiographs. Thus, the aim of the current study was to retrospectively assess a population of dogs with avascular necrosis of the femoral head in order to feature the disease, as well as to analyze the radiographic appearance of the lesion at the moment of patient consultation.Materials, Methods & Results: The signalment factors of dogs (breed, gender, age and body mass), the affected hind limb, the radiographic appearance of the lesion, the clinical signs at the moment of patient consultation, the time of occurrence and the type of treatment were evaluated. The disease was radiographically classified according to the previously described items. Forty-three cases of avascular necrosis of the femoral head were identified, 97.67% presented lameness and pain during palpation of the hip joint; and 54.34%, were 1 week to 4 months old. Females represented 58.13% of the sample, and 65.11% of them weighed from 2.6 to 4.9 kg. Based on the radiographic classification, 4.34% were Grade 1; 32.60%, Grade 2; 8.69%, Grade 3; 19.56%, Grade 4; and 34.78%, Grade 5. The femoral head and neck ostectomy was performed in 42 hind limbs (91.30%); 42.85% of the dogs reached total functional recovery and 26.19% required physiotherapy and rehabilitation.Discussion: The present sample was composed of 25 dogs, which were 6-to-11-month old at the moment of patient consultation, but 17 dogs were 12-to-36-month old at this time; only one dog was older than 36 months. It may be associated with the non-recognition of clinical signs by the owners, rather than with the late-onset form of the disease. With respect to the breed, pinscher, Yorkshire, poodle, Lhasa apso, pug were most frequently observed. However, 7 dogs were crossbreed. Such group differed from that of a review involving 188 cases encompassing West Highland white terrier, Cairn terrier and poodle as the most commonly affected breeds. No sex predilection was found in a study comprising 188 cases, but in another study comprising 14 dogs, female predilection was observed. Likewise, the females represented 58.13% of cases in the present study; and 41.86% of the participants were male. The mean body mass of the dogs in the current study was 4.33 kg, which matches the small breed dogs, which are most affected by the disease. Clinical signs of non-weightbearing lameness or an intermittent subtle lameness are common in the avascular necrosis of the femoral head. Lameness of the affected hind limb was observed in 69.76% of the cases in the present study, but 2.32% showed no lameness. Occasionally, the avascular necrosis of the femoral head is bilaterally found in 12% to 16.5% of the cases. Only 3 out of the 43 cases assessed in the present study were bilateral. Since the lesions were more frequent in Grades 2 and 5, there is less chance of success through the conservative treatment. Thus, the femoral head and neck ostectomy was the surgical procedure performed in 42 hind limbs. The procedure is used to provide pain relief and to reduce the signs of lameness. In conclusion, the population assessed in the present study was composed of small size dogs, mean body mass 4.33 kg, no sex predilection, mostly presenting unilateral lesions and higher Grade 2 and Grade 5 radiographic lesion frequency.Keywords: radiographic, joint, canine, hip.


2020 ◽  
pp. 561-569
Author(s):  
Angeliki Chandrinou ◽  
◽  
Anna Korompeli ◽  
Eirini Grammatopoulou ◽  
Konstantina Gaitanou ◽  
...  

Introduction: The treatment of avascular necrosis of the femoral head (AVNFH) is based on invasive (e.g., core decompression) and non-invasive methods (e.g., hyperbaric oxygen therapy – HBO2). The purpose of the present study is to evaluate the effect of HBO2 on the quality of life (QoL) of patients with AVNFH. Methods: This was a prospective observational non-controlled study of patients with AVNFH treated by HBO2. It was conducted, with the use of Steinberg scale, on 73 patients with AVNFH Stage I or II who were treated with HBO2. Patients’ QoL was assessed with EuroQol-5D-5L (EQ), Harris Hip Score (mHHS), MAHORN (MHOT), and VAS, in three different phases: before HBO2; after the completion of the first phase (20 HBO2 sessions, up to two months); and after the completion of the second phase (20 HBO2 sessions, up to two months after the first phase). A reassessment was made on the completion of each phase. Ratings were also made after the completion of each phase, over the first five months of follow-up. Results: All 73 patients (67.1% males, 32.9% females, mean age: 40.34, SD ± 9.99) participated in the study. Steinberg scale, mean EQ (F (1, 57) = 25.18, η2 = .306 and F (1, 43) = 43.402, η2 = .502); mHHS (F (1, 61) = 67.13, η2 = .524) and F (1, 43) = 31.84, η2 = .425); MHOT (F (1, 61) = 11.68, η2 = .161) and F (1, 43) = 98.01, η2 = .695); and VAS (F (1, 53) = 24.11, η2 = .313) and F (1, 39) = 45.61, η2 = .539), improved between the first and second measurements and between the second and third measurement accordingly (p < .01). Conclusions: HBO2 treatment does not induce alteration of quality of life and is well tolerated and accepted by patients.


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