Transpedicular Intravertebral Cage Augmentation Using Expandable Cage in Kummell Disease: Technical Note and Case Series.

OBJECTIVE: To demonstrate the surgical techniques for transpedicular intravertebral cage augmentation (TPICA) using an expandable cage for Kummell disease, which requires posterior surgical stabilization, and provide the preliminary surgical outcomes. METHODS: Six consecutive patients undergoing TPICA surgery using an expandable cage with a minimum 6-month follow-up were evaluated. Radiographic analysis to evaluate the local kyphosis angle, restoration ratio of anterior vertebral height of the index vertebra, and clinical outcomes including the Oswestry Disability Index, EuroQol 5-dimension instrument, and visual analog scale for back and leg pain, were compared between the preoperative and final follow-ups. RESULTS: All patients showed improvements in all clinical outcomes and were able to walk independently without support at the last follow-up. In radiographic evaluation, the mean preoperative restoration ratio of anterior vertebral height was 41.2 ± 15.6%, which increased postoperatively to 70.3 ± 20.5% (1.70 times) and 62.4 ± 20.0% at the last follow-up (1.51 times). The mean preoperative local kyphosis angle was 10.5 ± 14.8 and was corrected to 6.0 ± 10.0 at the last follow-up. A slight loss of correction was observed between the postoperative period and the last follow-up; however, there was no clinical significance. CONCLUSIONS: Expandable cages in TPICA may allow easier surgical manipulation for cage insertion around the pedicle entrance, minimizing damage to the fractured vertebral body's end plates while achieving satisfactory height restoration compared to static cages, and may also provide wider indications for TPICA surgery.

Short chain fatty acids facilitate protective immunity by macrophages and T cells during acute fowl adenovirus-4 infection.

Short chain fatty acids (SCFAs) are major gut metabolites that are involved in the regulation of dysfunction in immune responses, such as autoimmunity and cytokine storm. Numerous studies have reported a protective action of SCFAs against infectious diseases. This study investigated whether SCFAs have protective effect for immunity during fowl adenovirus-4 (FAdV-4) infection. We examined whether SCFA mixture (acetate, propionate, and butyrate) administration could protect against intramuscular challenge of a virulent viral strain. SCFA treatment promoted MHCII-expressing monocytes, the active form of T cells, and effector molecules in both peripheral and lymphoid tissues. It also boosted the production of immune molecules involved in pathogen elimination by intraepithelial lymphocytes and changed the intestinal microbial composition. We suggest that gut metabolites influence the gut microbial environment, and these changes stimulate macrophages and T cells to fight against the intramuscular challenge of FAdV-4.

ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions.

Endoplasmic reticulum stress is closely associated with the onset and progression of inflammatory bowel disease. ERdj5 is an endoplasmic reticulum-resident protein disulfide reductase that mediates the cleavage and degradation of misfolded proteins. Although ERdj5 expression is significantly higher in the colonic tissues of patients with inflammatory bowel disease than in healthy controls, its role in inflammatory bowel disease has not yet been reported. In the current study, we used ERdj5-knockout mice to investigate the potential roles of ERdj5 in inflammatory bowel disease. ERdj5 deficiency causes severe inflammation in mouse colitis models and weakens gut barrier function by increasing NF-κB-mediated inflammation. ERdj5 may not be indispensable for goblet cell function under steady-state conditions, but its deficiency induces goblet cell apoptosis under inflammatory conditions. Treatment of ERdj5-knockout mice with the chemical chaperone ursodeoxycholic acid ameliorated severe colitis by reducing endoplasmic reticulum stress. These findings highlight the important role of ERdj5 in preserving goblet cell viability and function by resolving endoplasmic reticulum stress.

Critical diagnostic and cancer stem cell markers in neoplastic cells from canine primary and xenografted pulmonary adenocarcinoma.

It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.

Pulmonary toxicity of sodium dichloroisocyanurate after intratracheal instillation in sprague-dawley rats.

In water, sodium dichloroisocyanurate (NaDCC), a source for chlorine gas generation, releases free available chlorine in the form of hypochlorous acid, a strong oxidizing agent. NaDCC has been used as a disinfectant in humidifiers; however, its inhalation toxicity is a concern. Seven-week-old rats were exposed to NaDCC doses of 100, 500, and 2500 µg·kg-1 body weight by intratracheal instillation (ITI) to investigate pulmonary toxicity. The rats were sacrificed at 1 d (exposure group) or 14 d (recovery group) after ITI. Despite a slight decrease in body weight after exposure, there was no statistically significant difference between the control and NaDCC-treated groups. A significant increase in the total protein level of the bronchoalveolar lavage fluid (BALF) was observed in the exposure groups. Lactate dehydrogenase leakage into the BALF increased significantly (p < 0.01) in the exposure groups; however, recovery was observed after 14 d. The measurement of cytokines in the BALF samples indicated a significant increase in interleukin (IL)-6 in the exposure group and IL-8 in the recovery group. Histopathological examination revealed inflammatory foci and pulmonary edema around the terminal bronchioles and alveoli. This study demonstrated that ITI of NaDCC induced reversible pulmonary edema and inflammation without hepatic involvement in rats.

Acute Toxicity in the Rat Lung Induced by Intratracheal Instillation of Glycolic Acid.

BACKGROUND/AIM: Inhalation toxicity tests of glycolic acid, which is used in many household products, have been reported, but the pulmonary toxicity of glycolic-acid has not been confirmed. Here, the lung damage caused by glycolic acid was investigated in rats. MATERIALS AND METHODS: An intratracheal instillation test was performed with glycolic acid in male rats. Bronchoalveolar lavage fluid (BALF) and histopathological analysis were conducted to identify the pulmonary toxicities. RESULTS: Intratracheal instillation of glycolic acid caused weight loss in animals and increased the content of lactate dehydrogenase, total protein, polymorphonuclear neutrophils, and inflammatory cytokines in BALF. In addition, pulmonary edema, alveolar/interstitial inflammation, and necrosis and desquamation of bronchial/bronchiolar epithelia were confirmed via histopathological examination. CONCLUSION: Exposure to glycolic acid can be harmful and toxic to the lungs.

Comprehensive pulmonary toxicity assessment of cetylpyridinium chloride using A549 cells and Sprague-Dawley rats.

Cetylpyridinium chloride (CPC), a quaternary ammonium compound and cationic surfactant, is used in personal hygiene products such as toothpaste, mouthwash, and nasal spray. Although public exposure to CPC is frequent, its pulmonary toxicity has yet to be fully characterized. Due to high risks of CPC inhalation, we aimed to comprehensively elucidate the in vitro and in vivo toxicity of CPC. The results demonstrated that CPC is highly cytotoxic against the A549 cells with a half-maximal inhibitory concentration (IC50 ) of 5.79 µg/ml. Following CPC exposure, via intratracheal instillation (ITI), leakage of lactate dehydrogenase, a biomarker of cell injury, was significantly increased in all exposure groups. Further, repeated exposure of rats to CPC for 28 days caused a decrease in body weight of the high-exposure group and the relative weights of the lungs and kidneys of the high recovery group, but no changes were evident in the histological and serum chemical analyses. The bronchoalveolar lavage fluid (BALF) analysis showed a significant increase in proinflammatory cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α levels. ITI of CPC induced focal inflammation of the pulmonary parenchyma in rats' lungs. Our study demonstrated that TNF-α was the most commonly secreted proinflammatory cytokine during CPC exposure in both in vitro and in vivo models. Polymorphonuclear leukocytes in the BALF, which are indicators of pulmonary inflammation, significantly increased in a concentration-dependent manner in all in vivo studies including the ITI, acute, and subacute inhalation assays, demonstrating that PMNs are the most sensitive parameters of pulmonary toxicity.

In Vitro and In Vivo Evaluation of the Toxic Effects of Dodecylguanidine Hydrochloride.

The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be the most cytotoxic (IC50: 0.39 µg/mL), as determined by the water soluble tetrazolium salts (WST) assay. An acute inhalation study for DGH was conducted using Sprague-Dawley rats at 8.6 ± 0.41, 21.3 ± 0.83, 68.0 ± 3.46 mg/m3 for low, middle, and high exposure groups, respectively. The levels of lactate dehydrogenase, polymorphonuclear leukocytes, and cytokines (MIP-2, TGF-ß1, IL-1ß, TNF-α, and IL-6) in the bronchoalveolar lavage fluid increased in a concentration-dependent manner. Histopathological examination revealed acute inflammation with necrosis in the nasal cavity and inflammation around terminal bronchioles and alveolar ducts in the lungs after DGH inhalation. The LC50 of DGH in rats after exposure for 4 h was estimated to be >68 mg/m3. Results from the inhalation studies showed that DGH was more toxic in male rats than in female rats. Overall, DGH was found to be the most cytotoxic chemical among guanidine-based chemicals. Exposure to aerosols of DGH could induce harmful pulmonary effects on human health.

Balanced adhesion and cohesion of chitosan matrices by conjugation and oxidation of catechol for high-performance surgical adhesives.

Catechol-conjugated chitosan (CCs), used as tissue adhesive, wound dressing, and hemostatic materials, has been drawing much more attention. However, most CCs tissue adhesives exhibit poor adhesion strength, and few studies on optimization of cohesion and adhesion strength of CCs derivatives have been conducted. This work focused on the balance between cohesion and adhesion strength of catechol-conjugated chitosan (CCs) derivatives via different mechanisms of chemical and enzymatic conjugation. CCs derivatives were characterized regarding its mechanical property, cytotoxicity, platelet adhesion and wound healing test. Mechanical properties could be optimized by the degree of catechol substitution, pH and the presence of oxidizing agent, resulting in that the highest value of adhesive shear strength to the porcine tissue is 64.8 ± 5.7 kPa. In addition, CCs derivatives exhibit decreased toxicity and promoted in vivo wound healing effects as comparing to a commercially available adhesive (Dermabond®). All the results demonstrate that CCs derivatives can be used as well-optimized tissue adhesives as well as a hemostat.

Plasmacytoid dendritic cells regulate colitis-associated tumorigenesis by controlling myeloid-derived suppressor cell infiltration.

Toll-like receptor (TLR)3 and TLR7 are important for stimulating plasmacytoid dendritic cells (pDCs), which secrete type I interferon. Mice deficient for TLR3 and TLR7 (TLR3-/-TLR7-/-) reportedly exhibit deteriorated colitis because of impaired pDCs. However, the role of pDCs in tumorigenesis-associated inflammation progression has not been studied. We treated wild-type or TLR3-/-TLR7-/- mice with dextran sulfate sodium (DSS) and/or azoxymethane (AOM) and examined colon mucosa, measured body weight and colon length of mice, and examined pDC and myeloid-derived suppressor cell (MDSC) accumulation. Further, we depleted pDCs in AOM/DSS-treated wild-type mice by treating them with anti-PDCA-1 antibodies. We found that MDSCs significantly increased, while pDCs decreased in TLR3-/-TLR7-/- mice. Moreover, TLR3-/-TLR7-/- mice developed colitis-associated colon cancer following AOM/DSS treatment. Additionally, we showed that a defect in TLR7 of pDCs is responsible for the aggravation of colitis-associated colon cancer. Further, we showed that TLR7 ligand mitigates colitis-associated colon cancer. Collectively, our results demonstrate that gut pDCs play a crucial role in reducing colorectal cancer development via the regulation of infiltrating MDSCs.

In Vivo Toxicity and In Vitro Solubility Assessment of Pre-Treated Struvite as A Potential Alternative Phosphorus Source in Animal Feed.

Apart from using as fertilizer for plants, the application of struvite may be expanded to animal feed industries through proper pre-treatment. This study aimed to investigate the safety and efficacy of using pre-treated struvite (microwave irradiated struvite (MS) and incinerated struvite (IS)) in animal feeds. For safety assessment, an in vivo toxicity experiment using thirty female Sprague Dawley rats (average body weight (BW) of 200 ± 10 g) was conducted. The rats were randomly divided into five groups, including a control. Based on the BW, MS and IS were applied daily by oral administration with 1 and 10 mg kg-1-BW (MS1 and MS10; IS1 and IS10) using dimethyl sulfoxide (DMSO) as a vehicle. A series of jar tests were conducted for four hours to check the solubility of the MS and IS at different pH (pH 2, 4, and 5) and compared to a commercial P source (monocalcium phosphate, MCP, control). The toxicity experiment results showed no significant differences among the treatments in BW and organ (liver, kidney, heart, and lung) weight of rats (p > 0.05). There were no adverse effects on blood parameters and the histopathological examination showed no inflammation in the organ tissues in MS and IS treated groups compared to the control. In an in vitro solubility test, no significant difference was observed in ortho-phosphate (O-P) solubility from the MCP and MS at pH 2 and 4 (p > 0.05), while O-P solubility from MS at pH 5 to 7 was higher than MCP and found to be significantly different (p < 0.05). O-P solubility from IS was the lowest among the treatments and significantly different from MCP and MS in all the experiments (p < 0.05). The results of this study not only suggest that the struvite pre-treated as MS could be a potential alternative source of P in animal feed but also motivate further studies with more stringent designs to better examine the potential of struvite application in diverse fields.

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats.

BACKGROUND/AIM: The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats. MATERIALS AND METHODS: We conducted acute (~458 mg/m3) and sub-acute (~49.5 mg/m3) inhalation tests to identify the potential toxicities of glycolic acid. RESULTS: Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period. CONCLUSION: The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the end of a 28-day inhalation test in male rats.

Inhalation toxicity of benzalkonium chloride and triethylene glycol mixture in rats.

Benzalkonium chloride (BAC), a disinfectant, and triethylene glycol (TEG), an organic solvent/sanitizer, are frequently combined in commercially available household sprays. To assess the respiratory effect of this combination, Sprague-Dawley rats were exposed to an aerosol containing BAC (0.5%, w/v) and TEG (10%, w/v) for up to 2 weeks in a whole-body inhalation chamber. BAC (4.1-4.5 mg/m3, sprayed from 0.5% solution) promoted pulmonary cell damage and inflammation as depicted by the increase in total protein, lactate dehydrogenase, polymorphonuclear leukocytes, and macrophage inflammatory protein-2 in the bronchoalveolar lavage fluid, whereas TEG (85.3-94.5 mg/m3, sprayed from 10% solution) did not affect the lung. Rats exposed to the BAC/TEG mixture for 2 weeks showed severe respiratory symptoms (sneezing, wheezing, breath shortness, and chest tightness), but no lung damage or inflammation was observed. However, significant ulceration and degenerative necrosis were observed in the nasal cavities of rats repeatedly exposed to the BAC/TEG mixture. The mass median aerodynamic diameters of the aqueous, BAC, TEG and BAC/TEG aerosols were 1.24, 1.27, 3.11 and 3.24 µm, respectively, indicating that TEG-containing aerosols have larger particles than those of the aqueous and BAC alone aerosols. These results suggest that the toxic effects of BAC and BAC/TEG aerosols on the different respiratory organs may be associated with the difference in particle diameter, since particle size is important in determining the deposition site of inhaled materials.

Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems.

Benzalkonium chloride (BAC) is a widely used disinfectant/preservative, and respiratory exposure to this compound has been reported to be highly toxic. Spray-form household products have been known to contain BAC together with triethylene glycol (TEG) in their solutions. The purpose of this study was to estimate the toxicity of BAC and TEG mixtures to pulmonary organs using in vitro and in vivo experiments. Human alveolar epithelial (A549) cells incubated with BAC (1-10 µg/mL) for 24 hours showed significant cytotoxicity, while TEG (up to 1000 µg/mL) did not affect cell viability. However, TEG in combination with BAC aggravated cell damage and inhibited colony formation as compared to BAC alone. TEG also exacerbated BAC-promoted production of reactive oxygen species (ROS) and reduction of glutathione (GSH) level in A549 cells. However, pretreatment of the cells with N-acetylcysteine (NAC) alleviated the cytotoxicity, indicating oxidative stress could be a mechanism of the toxicity. Quantification of intracellular BAC by LC/MS/MS showed that cellular distribution/absorption of BAC was enhanced in A549 cells when it was exposed together with TEG. Intratracheal instillation of BAC (400 µg/kg) in rats was toxic to the pulmonary tissues while that of TEG (up to 1000 µg/kg) did not show any harmful effect. A combination of nontoxic doses of BAC (200 µg/kg) and TEG (1000 µg/kg) promoted significant lung injury in rats, as shown by increased protein content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluids (BALF). Moreover, BAC/TEG mixture recruited inflammatory cells, polymorphonuclear leukocytes (PMNs), in terminal bronchioles and elevated cytokine levels, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in BALF. These results suggest that TEG can potentiate BAC-induced pulmonary toxicity and inflammation, and thus respiratory exposure to the air mist from spray-form products containing this chemical combination is potentially harmful to humans.

Location and Correlation of Acetabular Labral Tears and Paralabral Cysts Using Magnetic Resonance Imaging or Magnetic Resonance Arthrography in Patients With Femoroacetabular Impingement.

PURPOSE: To evaluate the prevalence and location of paralabral cysts and the correlation between the type of femoroacetabular impingement (FAI) and acetabular labral tears, as well as the location of the paralabral cysts. METHODS: Patients who received a diagnosis of FAI syndrome using plain radiography, magnetic resonance imaging or magnetic resonance arthrography, or computed tomographic arthrography from 2010 to 2015 were included in this study. The exclusion criteria were patients with arthritis (Tönnis grade 2 or greater) or dysplasia. We identified paralabral cysts and their location, size, configuration. Correlations between the type of FAI and labral tears and paralabral cysts were analyzed using the χ-square test. RESULTS: Among 506 patients with FAI, paralabral cysts were found in 51 patients (55 hips) and were located anterosuperiorly in 40% of cases, posterosuperiorly in 36%, anteroinferiorly in 17%, and posteroinferiorly in 8%. We identified multilocular cysts in 60% of hips and unilocular cysts in 40%. Labral tears were radiographically found in 44 of 55 hips with paralabral cysts (80%); they were located anterosuperiorly in 59% and posterosuperiorly in 41%. Although paralabral cysts were found in the anteroinferior and posteroinferior areas, acetabular labral tears were not identified in the anteroinferior and posteroinferior areas. Classification of the type of FAI showed cam type in 14 of 55 hips (25.5%), pincer type in 16 (29%), mixed type in 7 (13%), labral tears in 15 (27%), and normal findings in 3 (5.5%). No correlation was found between the type of FAI and labral tears (P = .739) or the location of paralabral cysts (P = .228). CONCLUSIONS: Paralabral cysts in patients with FAI most commonly are found in the anterosuperior area and are of the multilocular type. Although paralabral cysts in the anterosuperior and posterosuperior portions are related to labral tears, those in the anteroinferior and posteroinferior portions are not. LEVEL OF EVIDENCE: Level IV, diagnostic case series.

Application of alginate microbeads as a carrier of bone morphogenetic protein-2 for bone regeneration.

Bone morphogenetic protein-2 (BMP-2) is commonly used to enhance bone regeneration. The potential of BMP-2 for bone regeneration varies according to the concentration and release kinetics on the implanted site. Therefore, it is important to determine appropriate carriers of BMP-2. However, no optimal delivery vehicles have been identified. In the present study, we used alginate microbeads as a delivery vehicle for BMP-2. Alginate microbeads can be implanted onto the disease site through surgery or injection. The objective of this study was to evaluate that the osteoinductive properties of BMP-2 are effective in alginate microbeads as a carrier. In this study, the release kinetics of BMP-2 in alginate microbeads was evaluated using an enzyme-linked immunosorbent assay. BMP-2 released from alginate microbeads induced high alkaline phosphatase activity in canine adipose tissue-derived mesenchymal stem cells. Injection of alginate microbeads with BMP-2 into mouse subcutaneous tissue, as well as surgical implantation into the 5-mm circular calvarial defects in rats, was conducted and the results showed extensive new bone formation. In conclusion, alginate microbeads can be utilized as an effective BMP-2 delivery vehicle for use in orthopedic surgery and as an injectable vehicle for a minimally invasive therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 286-294, 2019.

Potentiation of Sodium Metabisulfite Toxicity by Propylene Glycol in Both in Vitro and in Vivo Systems.

Many consumer products used in our daily lives result in inhalation exposure to a variety of chemicals, although the toxicities of the active ingredients are not well known; furthermore, simultaneous exposure to chemical mixtures occurs. Sodium metabisulfite (SM) and propylene glycol (PG) are used in a variety of products. Both the cytotoxicity and the sub-acute inhalation toxicity of each chemical and their mixtures were evaluated. Assays for cell viability, membrane damage, and lysosome damage demonstrated that SM over 100 µg/ml induced significant cytotoxicity; moreover, when PG, which was not cytotoxic, was mixed with SM, the cytotoxicity of the mixture was enhanced. Solutions of 1, 5, and 20% SM, each with 1% PG solution, were prepared, and the whole body of rats was exposed to aerosols of the mixture for 6 h/day, 5 days/week for 2 weeks. The rats were sacrificed 1 (exposure group) or 7 days (recovery group) after termination of the exposure. The actual concentration of SM in the low-, medium-, and high-exposure groups was 3.91 ± 1.26, 35.73 ± 6.01, and 80.98 ± 5.47 mg/m3, respectively, and the actual concentration of PG in each group was 6.47 ± 1.25, 8.68 ± 0.6, and 8.84 ± 1.77 mg/m3. The repeated exposure to SM and PG caused specific clinical signs including nasal sound, sneeze, and eye irritation which were not found in SM single exposure. In addition, the body weight of treatment group rats decreased compared to that of the control group rats in a time-dependent manner. The total protein concentration and lactate dehydrogenase activity in the bronchoalveolar lavage fluid (BALF) increased. Histopathological analysis of the lungs, liver, and nasal cavity was performed. Adverse effects were observed in the nasal cavity, with squamous cell metaplasia identified in the front of the nasal cavity in all high-exposure groups, which completely recovered 7 days after exposure was terminated. Whereas inhalation of SM for 2 weeks only reduced body weight in the high-dose group, inhalation of SM and PG mixtures for 2 weeks significantly decreased body weight and induced metaplasia of the respiratory epithelium into squamous cells in the medium- and high-dose groups. In conclusion, PG potentiated the toxicity of SM in human lung epithelial cells and the inhalation toxicity in rats.

Exogenous recombinant human thioredoxin-1 prevents acetaminophen-induced liver injury by scavenging oxidative stressors, restoring the thioredoxin-1 system and inhibiting receptor interacting protein-3 overexpression.

Thioredoxin-1 (Trx-1) is a potent therapeutic agent against a variety of diseases because of its actions as an antioxidant and regulator of apoptosis. N-acetyl-p-aminophenol (APAP), commonly known as acetaminophen, generates excessive oxidative stress and triggers hepatocyte cell death, exemplified by regulated necrosis. In the present study, we investigated whether APAP-induced liver injury in a mouse model is associated with "necroptosis," and if pretreatment with recombinant Trx-1 prevents the hepatic injury caused by APAP overdose. We also explored the mechanism underlying the preventive action of Trx-1 against APAP-induced hepatic injury. In a prevention study, C3H/he mice received different doses (0, 10, 50 or 100 mg kg-1 body weight) of recombinant human Trx-1 intraperitoneally, followed by a single oral dose of 300 mg kg-1 of APAP. In this experimental paradigm, liver injury and lethality were markedly decreased in rhTrx-1-pretreated mice. In survival experiments, mice received rhTrx-1 followed by oral administration of a lethal dose of APAP. APAP overdose caused a series of liver toxicity-associated events, beginning with overexpression of c-fos, excessive production of reactive oxygen species and reactive nitrogen species (RNS) and leading to decreased endogenous Trx-1 expression and activation of JNK signaling pathways. Pretreatment with rhTrx-1 inhibited all of these toxicological manifestations of APAP. In addition, rhTrx-1 significantly reduced the expression of RIP-3, a critical necrosome component. Taken together, our findings indicate that rhTrx-1 prevents APAP-induced liver injury through multiple action mechanisms, including scavenging reactive oxygen species and reactive nitrogen species, restoring endogenous Trx-1 levels and inhibiting RIP-3 overexpression.

Repair of rabbit radial bone defects using bone morphogenetic protein-2 combined with 3D porous silk fibroin/ß-tricalcium phosphate hybrid scaffolds.

Our study aimed to investigate the effect of bone morphogenetic protein-2 (BMP-2) bound to silk fibroin and ß-tricalcium phosphate (SF/ß-TCP) hybrid on the healing of critical-size radial defects in rabbits. A 15-mm critical-size defect was induced at mid-diaphysis in the left radius of 20 New Zealand white rabbits (average age, 3.5 months; weight, 2.5-3.0 kg). The animals were randomized into Group 1 (SF/ß-TCP combined with BMP-2), Group 2 (SF/ß-TCP alone), and Group 3 (nothing implanted). Radiographs were obtained every 2 weeks and euthanasia was performed after 8 weeks for visual, radiological, micro-computed tomography (micro-CT), and histological studies. Eight weeks after implantation (SF/ß-TCP combined with BMP-2), radiographs showed that new bone formed on the surface of the implant and had bridged the defect in Group 1. Micro-CT imaging also confirmed the formation of new bone around the implant, and the newly formed bone was quantified. Histological examination revealed newly formed bone in the implanted area. Meanwhile, there was no formation of new bone in Group 3. Among the groups, most active formation of new bones was found in Group 1, while there was no difference between Group 2 and Group 3. Based on these results, we concluded that BMP-2-SF/ß-TCP showed significant improvement in healing of critical-size defects. Therefore, the combination of BMP-2 and SF/ß-TCP would be useful in the field of bone tissue engineering.

The Radiologic Comparison of Operative Treatment Using a Hook Plate versus a Distal Clavicle Locking Plate of Distal Clavicle Fracture.

BACKGROUND: The purpose of this study was to compare the radiologic results of patients who underwent surgery with a hook plate and a locking plate in distal clavicle fractures. METHODS: Sixty patients underwent surgical treatment for Neer type IIa, IIb, III, and V distal clavicle fracture. Twenty-eight patients underwent fracture fixation with a hook plate and 32 with a locking plate. Coracoclavicular distance was measured on standard anteroposterior radiographs before and after the surgery, and union was confirmed by radiograph or computed tomography taken at 6 months postoperatively. Other radiologic complications like osteolysis was also checked. RESULTS: Bony union was confirmed in 59 patients out of 60 patients, and 1 patient in the hook plate group showed delayed union. Coracoclavicular distance was decreased more in the hook plate group after surgery (p<0.01). After 6 weeks of the hook plate removal, the coracoclavicular distance was increased a little compared to before metal removal, but there was no difference compared to the contralateral shoulder. Eleven out of 28 patients (39.3%) showed osteolysis on the acromial undersurface in the hook plate group. CONCLUSIONS: Both the hook plate group and the locking plate group showed satisfactory radiologic results in distal clavicle fractures. Both hook plate and locking plate could be a good treatment option if it is used in proper indication in distal clavicle fracture with acromioclavicular subluxation or dislocation.