Magnetic resonance imaging and computerised tomography findings in an intraspinal extradural hydatid cyst mimicking tuberculous spondylitis: a case report

Spinal hydatid cyst with thoracic vertebra involvement is rare but serious condition. We present a 63-year old woman with spinal hydatid disease mimicking tuberculous spondylitis. A case study with Computerised Tomography and Magnetic Resonance Imaging diagnostic findings and surgical treatment is reported in this article. Primary spinal hydatid disease should be considered in the differential diagnosis of tuberculous spondylitis in endemic area. Familiarity with typical imaging appearances of spinal hydatid disease may be helpful in making a correct diagnosis and treatment

The proper class generated by weak supplements

We show that, for hereditary rings, the smallest proper classes containing respectively the classes of short exact sequences determined by small submodules, submodules that have supplements and weak supplement submodules coincide. Moreover, we show that this class can be obtained as a natural extension of the class determined by small submodules. We also study injective, projective, coinjective and coprojective objects of this class. We prove that it is coinjectively generated and its global dimension is at most 1. Finally, we describe this class for Dedekind domains in terms of supplement submodules.TUBITAK (107T709

Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis

The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future

Flavopiridol Protects Bone Tissue by Attenuating RANKL Induced Osteoclast Formation.

Bone resorption and homeostasis is carried out by osteoclasts, whose differentiation and activity are regulated by the RANK/RANKL axis. Our previous studies using a mouse model of joint injury show that joint trauma induces local inflammation followed by bone remodeling. The transcription factor cyclin-dependent kinase 9 (CDK9) is the major regulator of inflammation, as CDK9 inhibitor flavopiridol effectively suppress injury-induced inflammatory response. The objective of this study was to investigate the underlying mechanism through which flavopiridol regulates bone resorption. The effects of CDK9 inhibition, by the specific-inhibitor flavopiridol, on bone resorption were determined in vivo using two distinct and clinically relevant bone remodeling models. The first model involved titanium particle-induced acute osteolysis, and the second model was ovariectomy-induced chronic osteoporosis. The effects and mechanism of CDK9 inhibition on osteoclastogenesis were examined using in vitro culture of bone marrow macrophages (BMMs). Our results indicated that flavopiridol potently suppressed bone resorption in both in vivo bone-remodeling models. In addition, CDK9 inhibition suppressed in vitro osteoclastogenesis of BMM and reduced their expression of osteoclast-specific genes. Finally, we determined that flavopiridol suppressed RANKL signaling pathway via inhibition of p65 phosphorylation and nuclear translocation of NF-κB. Summary, CDK9 is a potential therapeutic target to prevent osteolysis and osteoporosis by flavopiridol treatment

Effects of annulus defects and implantation of poly(lactic-co-glycolic acid) (PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degeneration

Abstract Background Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs. Methods New Zealand white rabbits (n = 24) received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter; 4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG) content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5. Results Injured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues. Conclusions Nerve ingrowth was significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible explanations include (i) annular fissures along the defect and early loss of proteoglycan may facilitate the ingrowth process and (ii) biodegradable PLGA/fibrin gel may promote adverse growth of nerves and blood vessels into deeper parts of injured disc. The rabbit annular defect model of disc degeneration appears suitable to investigate the effects of nerve ingrowth in relation to pain generation

Flavopiridol Protects Bone Tissue by Attenuating RANKL Induced Osteoclast Formation

Bone resorption and homeostasis is carried out by osteoclasts, whose differentiation and activity are regulated by the RANK/RANKL axis. Our previous studies using a mouse model of joint injury show that joint trauma induces local inflammation followed by bone remodeling. The transcription factor cyclin-dependent kinase 9 (CDK9) is the major regulator of inflammation, as CDK9 inhibitor flavopiridol effectively suppress injury-induced inflammatory response. The objective of this study was to investigate the underlying mechanism through which flavopiridol regulates bone resorption. The effects of CDK9 inhibition, by the specific-inhibitor flavopiridol, on bone resorption were determined in vivo using two distinct and clinically relevant bone remodeling models. The first model involved titanium particle-induced acute osteolysis, and the second model was ovariectomy-induced chronic osteoporosis. The effects and mechanism of CDK9 inhibition on osteoclastogenesis were examined using in vitro culture of bone marrow macrophages (BMMs). Our results indicated that flavopiridol potently suppressed bone resorption in both in vivo bone-remodeling models. In addition, CDK9 inhibition suppressed in vitro osteoclastogenesis of BMM and reduced their expression of osteoclast-specific genes. Finally, we determined that flavopiridol suppressed RANKL signaling pathway via inhibition of p65 phosphorylation and nuclear translocation of NF-κB. Summary, CDK9 is a potential therapeutic target to prevent osteolysis and osteoporosis by flavopiridol treatment

Association between Modic changes and endplate sclerosis: Evidence from a clinical radiology study and a rabbit model

Purpose: To analyse the presence of endplate sclerosis in patients with various types of Modic changes (MCs) and to confirm the results using a rabbit model. Methods: Participants in the clinical study included 1023 consecutive inpatients with lumbar degenerative disease who attended the Department of Orthopaedics between August 2011 and August 2015. All patients underwent computed tomography (CT) and magnetic resonance imaging of the lumbar spine. In those patients with MCs, endplate sclerosis was evaluated from sagittally reconstructed CT images. In addition to the clinical study, MCs type I, II and III were initiated using a previously developed rabbit model of MCs. Specimens of MCs type I, II and III and normal endplates were harvested, bone mineral density and bone volume/tissue volume of “treated” vertebrae were evaluated using μCT and osteogenic protein expressions of runt-related transcription factor 2 and osteocalcin were assessed using immunohistochemical staining. Measurements were compared between vertebrae with normal endplates and those with different types of MCs. Results: Of 1023 patients, 214 (20.9%) had MCs in one or more endplates; these changes affected 1044 (10.2%) of 10230 endplates. Type I, II and III MCs were seen in 164 (1.6%), 838(8.2%) and 40 (0.4%) endplates, respectively. Of 1044 endplates with MCs, 274 (26.2%) showed evidence of sclerosis on CT images including: 26/164 endplates (15.8%) with type I MCs, 208/838 (24.8%) with type II and 40/40 (100%) with type III. HU (CT value) ratios for sclerotic and nonsclerotic endplates with MCs were 2.0 ± 0.3 and 1.1 ± 0.1, respectively. In the animal study, the bone mineral density, bone volume/tissue volume and expression of runt-related transcription factor 2 and osteocalcin of endplates with type I and II MCs were higher than those of normal endplates and lower than those of endplates with type III MCs. Conclusion: Sclerosis can occur in endplates with any type of MCs. However, the clinical and animal study suggests that sclerosis is greatest in endplates showing type III MCs. The translational potential of this article: The study showed that sclerosis can occur in endplates with MCs type I, II and III. In patients with endplate sclerosis on plain radiographs or CT scans, the endplate can still represent an inflammatory process associated with chronic lower back pain. Keywords: Computed tomography, Endplate sclerosis, Magnetic resonance imaging, Modic change