A case report: white cord syndrome following anterior cervical discectomy and fusion: importance of prompt diagnosis and treatment.

BACKGROUND: Objective: White cord syndrome is extremely rare and search of the literature has revealed very few cases. Postoperative MR scan revealed hyperintense intrinsic cord signal changes within cord ischemia and edema. It is thought to be caused by reperfusion injury of the spinal cord. This is called white cord syndrome. This report is very rare case of 'White Cord Syndrome' with paraplegia after anterior cervical discectomy and fusion (ACDF). CASE PRESENTATION: A 49-year-old woman presented with neck pain lasting for several months and second and third finger radiating pain. Severe cervical herniated intervertebral disc findings could be identified at C6-7 level on C-spine MRI. ACDF C6-7 surgery was performed. Immediately after the operation, physical examination revealed paraplegia and emergency MRI was performed. On MR images, T2 high signal myelopathy suspected as reperfusion injury at C6-7 level, and emergency surgery was performed under diagnosis of white cord syndrome. After the emergency operation, the paraplegic problem was gradually resolved. Before discharge, motor power and sensory deficit of bilateral lower extremity were fully recovered. CONCLUSION: Surgeons should explain the possibility of white cord syndrome before cervical decompression surgery and should perform a neurological examination immediately after surgery. We recommend that the importance of early recognition and prompt treatment of white cord syndrome.

Induction of Heat Shock Proteins and Antioxidant Enzymes in 2,3,7,8-TCDD-Induced Hepatotoxicity in Rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, α-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (α-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

Clinical Characteristics of Elderly People with Osteoporotic Vertebral Compression Fracture Based on a 12-Year Single-Center Experience in Korea.

In an aging human population, osteoporotic vertebral compression fracture (OVCF) frequently occurs. We conducted this retrospective study to analyze the clinical characteristics of elderly people with OVCF who underwent percutaneous vertebroplasty or kyphoplasty over a 12-year period at a single medical center in Korea. Between 2007 and 2019, A total of 868 patients (n = 868) were treated at our institution. We assessed 600 of these patients as eligible for study purposes and divided them into three groups: Group A (spine and hip T-scores ≤-2.5; n = 332); Group B (spine T-scores ≤-2.5; n = 189); and Group C (hip T-scores ≤-2.5; n = 79). The baseline characteristics of the patients included age, sex, body mass index (BMI), past history of steroid use, alcohol consumption, use of osteoporosis therapy, smoking, and treatment for OVCF. We compared these characteristics between the three groups. We found that the mean patient age was significantly higher in Group A, compared with Group B, and significantly lower in Group B, compared with Group C. We also found significant differences in the male-to-female ratio and mean body mass index between the three groups. In conclusion, we suggest that special attention should be paid to factors closely associated with spine and hip T-scores when evaluating elderly people with OVCF and determining appropriate treatment.

Posterior pelvic ring injury of straddle fractures: Incidence, fixation methods, and clinical outcomes.

Straddle fracture, a superior and inferior ramus fracture of both sides, is generally treated conservatively. However, posterior pelvic ring injury is often associated with straddle fracture, leading to unstable pelvic bone fracture that requires surgical treatment. The present study reports the clinical and radiological outcomes of straddle fracture with posterior pelvic ring injury. This study included 73 patients (41 men, 32 women) with a straddle fracture injury. The injury mechanism, injury severity score (ISS), accompanying injuries, presence of posterior pelvic ring injury, and fixation methods for the pelvic fracture were analyzed, and outcomes were evaluated functionally and radiologically. Of the 73 patients, 56 (77%) had a posterior pelvic ring injury and 7 died. In 43 patients, the posterior pelvic ring injuries constituted unstable pelvic injury and were treated surgically. The fixation method was determined based on the severity of the posterior pelvic injury. The patients' mean ISS was 24.7 points. Radiological evaluation of surgical outcomes in 43 patients revealed the outcomes as anatomic in 20, nearly anatomic in 14, moderate in 5, and poor in 4, whereas functional evaluation revealed the outcomes as excellent in 21, good in 9, fair in 7, and poor in 6. Posterior pelvic ring fracture can accompany straddle fractures, which may lead to pelvic injury instability. Thus, special attention is required for patients with a straddle fracture.

Neuroglobin protects PC12 cells against oxidative stress.

Neuroglobin (Ngb) is a newly discovered globin in the vertebrate brain that exhibits neuroprotection against hypoxic/ischemic injury. Hypoxic/ischemic brain injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS), and antioxidants or ROS scavengers promote cell survival. Therefore, Ngb may serve as a scavenger of toxic reactive species, such as hydrogen peroxide. To examine the anti-oxidative role of neuroglobin, PC12 cells were transfected with wild type and mutant (H64 V/H96A) Ngb for 48 h and then treated with H2O2 (0.1, 0.2 and 0.4 mM) for 6 h. Ngb siRNA decreased the H2O2-induced Ngb expression and exacerbated H2O2-induced cell injury. Transient transfection of Ngb induced dose-dependent increases in Ngb protein expression and did not alter SOD, GPX, and catalase activities. Overexpression of wild type Ngb, but not of mutant Ngb, significantly attenuated H2O2-induced ROS/RNS accumulation and lipid peroxidation, decreased H2O2-induced mitochondrial dysfunction and apoptosis, and promoted overall cell survival. Thus, Ngb plays a protective role against oxidative stress, which appears to be primarily mediated by intrinsic Ngb antioxidant properties.

Hypoxia differentially regulates the expression of neuroglobin and cytoglobin in rat brain.

Neuroglobin (Ngb) and Cytoglobin (Cygb) are new members of the globin family and display heterotopic expression patterns. To examine the effect of different hypoxia profiles on expression of Ngb and Cygb in rodent brain, rats were exposed to either sustained hypoxia (SH; 10% O(2)) or intermittent hypoxia (IH; 10% and 21% O(2) alternating every 90 s) for 1, 3, 7 and 14 days, and mRNA and protein expression of Ngb and Cygb were assessed in brain cortex. SH increased Ngb mRNA and protein expression throughout the exposure, while IH only elicited slight increases in Ngb expression at day 1. Neither SH nor IH elicited increases in Cygb expression. Thus, hypoxic stimulus presentation is a major determinant of the regulation of hypoxic sensitive genes such as Ngb. Furthermore, disparities between Ngb and Cygb responses to hypoxia further suggest that these two globins may play divergent roles in brain.

The flavonoid glabridin attenuates 2-deoxy-D-ribose-induced oxidative damage and cellular dysfunction in MC3T3-E1 osteoblastic cells.

Reducing sugar 2-deoxy-D-ribose (dRib) produces reactive oxygen species (ROS) through autoxidation and protein glycosylation and causes dysfunction of osteoblasts. In the present study, glabridin, a natural flavonoid, was investigated to determine whether it could influence dRib-induced oxidative damage and cellular dysfunction in the MC3T3-E1 mouse osteoblastic cell line. Osteoblastic cells were treated with dRib in the presence or absence of glabridin. Cell viability, apoptosis, ROS production and mitochondrial membrane potential (ΔΨm) were subsequently examined. It was observed that dRib reduced cell survival and ΔΨm, while it markedly increased intracellular levels of ROS and apoptosis. However, pretreatment of cells with glabridin attenuated all the dRib-induced effects. The antioxidant N-acetyl-L-cysteine (NAC) also prevented dRib-induced oxidative cell damage. In addition, treatment with glabridin resulted in a significant elevation of alkaline phosphatase (ALP) activity, collagen contents and osteoblast differentiation genes [ALP, collagen, osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC)] and bone morphogenetic protein (BMP) genes (BMP2, BMP4 and BMP7). In mechanistic studies of the antioxidative potential of glabridin, we found that glabridin activated dRib-induced decreased expression of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B 2 (AKT2) genes, which are master regulators of survival-related signaling pathways. Glabridin also upregulated the gene expression of antioxidant enzymes, superoxide dismutase 1 (SOD1) and glutathione peroxidase 4 (GPX4), which were inhibited by dRib. Taken together, these results suggest that glabridin attenuates dRib-induced cell damage in osteoblastic cells and may be useful for the treatment of diabetes-related bone disease.

Papillary thyroid carcinoma with bone formation.

Bone formation is a rarely encountered finding during histological examination of papillary thyroid carcinoma (PTC). This study aimed to analyze clinicopathological parameters in patients with PTC showing bone formation, to document histological features of bone formation in PTC, and to investigate osteogenic proteins. Bone morphogenic protein (BMP)-9 is known as the most potent osteoinductive protein of the BMP subtypes. Recent research suggests that the activin receptor-like kinase (ALK) 1 is an essential cellular receptor that mediates BMP-9-induced osteogenic signaling. A retrospective review of tumor sections from 567 patients with a diagnosis of PTC was performed. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of ALK1 and BMP-9 in normal thyroid tissue and PTC samples with and without bone formation. Bone formation was found in 13% of patients with PTC. A significant association was seen between bone formation and old age. BMP-9 expression in tumors was increased compared to that in normal thyroid tissues. BMP-9 expression in tumors with bone formation was not significantly different from that in tumors without bone formation. ALK1 expression in tumors with bone formation was increased compared to that in normal thyroid tissue and tumors without bone formation. Our study suggests that upregulation of ALK1 might be an underlying molecular mechanism that explains osteogenesis in PTC.

MicroRNA-199b-5p is involved in the Notch signaling pathway in osteosarcoma.

MicroRNAs (miRNAs) play important roles in the development, differentiation, and function of different cell types and in the pathogenesis of various human diseases. miRNAs are differentially expressed in normal and cancer cells. The investigation of miRNA expression between healthy subjects and patients with osteosarcoma is crucial for future clinical trials. We performed miRNA microarray analysis on 8 formalin-fixed, paraffin-embedded osteosarcoma tissue samples. We confirmed the results of the microarray analysis using reverse transcription polymerase chain reaction. miRNA profiling of osteosarcoma tissue samples showed that expression of 10 miRNAs had increased 10-fold compared with normal controls. Among the 10 miRNAs, 3 miRNAs (miR-199b-5p, miR-338-3p, and miR-891a) were confirmed to have been up-regulated by reverse transcription polymerase chain reaction. After transfection of 4 osteosarcoma cell lines with miR-199b-5p inhibitor, the expression of Notch pathway components in the transfected cell lines was changed. These results revealed that miR-199b-5p plays a role in Notch signaling in osteosarcoma. Recently, the inhibition of Notch and HES1 signaling has been suggested as a potential therapeutic strategy to prevent metastasis in human osteosarcoma. Taken together with our results, we suggest that miR-199b-5p inhibitor may also be a therapeutic option for osteosarcoma.

Novel Mutation in PRKAR1A in Carney Complex.

A case of Carney complex in a Korean patient is presented. The patient had the characteristics of Carney complex including skin lesions, positive family history, and multiple myxomas including a superficial angiomyxoma in the perianal area. An extensive genetic analysis revealed a novel mutation in the protein kinase A type I-a regulatory subunit (PRKAR1A) gene, but not in the phosphodiesterase type 11A (PDE11A) gene. This is the first case wherein extensive genetic studies were performed in a patient with Carney complex in Korea.

The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells.

Osteoblastic bone formation and osteoclastic bone resorption are in balance to maintain a constant, homeostatically controlled amount of bone. Excessive bone resorption by osteoclasts is involved in the pathogenesis of bone-related disorders. In the present study, we evaluated the inhibitory effects of glabridin, a flavonoid purified from licorice root, on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and its molecular mechanisms in murine osteoclast progenitor RAW264.7 cells. Glabridin significantly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, the formation of multinucleated osteoclasts and resorption-pit formation. In mechanistic studies of the anti-osteoclastogenic potential of glabridin, we found that glabridin inhibited RANKL-induced expression of c-Fos and subsequent expression of NFATc1, which is a master regulator of osteoclastogenesis. Interestingly, glabridin inhibited the RANKL-induced expression of signaling molecules (TRAF6, GAB2, ERK2, JNK1 and MKK7) and osteoclast survival-related signaling pathways such as c-Src, PI3K and Akt2. Glabridin also inhibited the bone resorptive activity of mature osteoclasts by inhibiting osteoclast-associated genes (cathepsin K, MMP-9, CAII, TCIRG1, OSTM1 and CLCN7). Taken together, our data suggest that glabridin holds great promise for use in preventing osteoclastogenesis by inhibiting RANKL-induced activation of signaling molecules and subsequent transcription factors in osteoclast precursors and these findings may be useful for evaluating treatment options in bone-destructive diseases.

Neuroglobin protects neurons against oxidative stress in global ischemia.

Neuroglobin (Ngb) is a recently discovered globin that affords protection against hypoxic/ischemic-induced cell injury in brain. Hypoxic/ischemic injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). In previous studies, we found that Ngb has antioxidative properties, and protects PC-12 cells against hypoxia- and ß-amyloid-induced cell death. To further delineate the potential role of Ngb in protection against cerebral ischemia-reperfusion injury in vivo, we developed a transgenic mouse line that overexpresses Ngb. Hippocampal ischemia-reperfusion injury was induced by a 10-minute bilateral occlusion of the common carotid arteries, and the animal brains were assessed 3 days later. CA1 neural injury was determined by cresyl violet staining. Lipid peroxidation was assessed using a malonyldialdehyde assay kit, whereas ROS/RNS accumulation was determined by Het staining in the CA1 hippocampal region. Hippocampal Ngb mRNA and protein expressions were assessed by reverse transcriptase-PCR and western blotting, respectively. Neuroglobin was successfully overexpressed in the hippocampus of Ngb transgenic mice. After ischemia-reperfusion, CA1 ROS/RNS production and lipid peroxidation were markedly decreased in Ngb transgenic mice compared with wild-type mice. Furthermore, CA1 neuronal injury was also markedly reduced. Thus, Ngb may confer protection against ischemia-reperfusion injury in the brain through its intrinsic antioxidant properties.

Neuroglobin protects PC12 cells against beta-amyloid-induced cell injury.

Excessive accumulation of amyloid beta (Abeta) has been proposed as a pivotal event in the pathogenesis of Alzheimer's disease. Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excess production of reactive oxidative species (ROS) and apoptosis. Neuroglobin (Ngb), a newly discovered globin in vertebrates that exhibits neuroprotective functions, may have a potential role in scavenging ROS. To examine the potential protective role of Ngb in Abeta-induced cytotoxicity, PC12 cells were treated with Abeta (1-42 fragment) for 24h. Abeta treatments increased ROS production in PC12 cells. Overexpression of Ngb but not Ngb mutant in the PC12 cells significantly attenuated Abeta-induced ROS production and lipids peroxidation. Furthermore, overexpression of Ngb also attenuated Abeta-induced mitochondrial dysfunction and apoptosis, and promoted cell survival in PC12 cells. Therefore, Ngb may act as an intracellular ROS scavenger, and such antioxidant properties may play a protective role against Abeta-induced cell injury.