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.

Safety and Efficacy Assessment of Red Ginseng Oil (RXGIN) in Men with Lower Urinary Tract Symptoms in a Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of red ginseng oil (RXGIN) in men with lower urinary tract symptoms. MATERIALS AND METHODS: Men aged between 40 and 75 years with a total International Prostate Symptom Score (IPSS) of 8 to 19 points were recruited from April 2020 to December 2020. Subjects were randomly assigned to either the RXGIN group or the control group in a 1:1 ratio and received either RXGIN or placebo daily for 12 weeks. For the primary outcome, changes in IPSS scores at 6 and 12 weeks from baseline were analyzed. The secondary outcomes were changes in International Index of Erectile Function (IIEF), maximum urinary flow rate, and post-void residual volume at weeks 6 and 12 compared to baseline. Urine analysis and blood tests were additionally performed for safety assessment. RESULTS: A total of 88 subjects (RXGIN group, 46; control group, 42) completed the study. The total IPSS and IPSS subscores (residual urine sensation, frequency, intermittency, urgency, weak stream, straining, nocturia, and quality of life) were significantly improved in the RXGIN group compared to the control group at weeks 6 and 12. Total IIEF and sexual desire were significantly improved in the RXGIN group at week 6 and week 12, respectively, but there were no significant changes in the level of serum testosterone or dihydrotestosterone. The serum prostate-specific antigen showed significant decrease at weeks 12. No serious adverse events leading to discontinuation of the study drug were observed in the RXGIN group. CONCLUSIONS: Red ginseng oil (RXGIN) appears to be safe and effective in improving lower urinary tract symptoms in men and may also improve some aspects of sexual function.

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.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial.

Background: To evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methods: From November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12-19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. Results: A total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. Conclusions: CAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.

Impact of age and metabolic syndrome-like components on prostate cancer development: a nationwide population-based cohort study.

BACKGROUND: Because of the contradictory results, more epidemiologic data is needed to determine if metabolic syndrome is a risk factor for developing prostate cancer. This study investigated whether metabolic syndrome-like components affect the incidence of prostate cancer in a Korean population. METHODS: Men over 50 years of age who underwent health examinations in 2009 were followed until December 2015 (n=1,917,430) using National Health Insurance System data. Subjects were divided into three groups according to the number of metabolic syndrome-like components. The predictive accuracy of age for prostate cancer was assessed by the Youden index and multivariate adjusted Cox regression analysis was used to analyze the effect of metabolic syndrome-like components on prostate cancer development. RESULTS: The risk of prostate cancer increases with age, and the best cutoff age for prostate cancer detection was 62 years (the maximum value of the Youden index). When stratified by the number of metabolic syndrome-like components, the age with the highest Youden index of each group is still 61 or 62 years. In multivariate adjusted Cox regression analysis, there was no statistically significant difference in the incidence rate among the non-component group, the group with 1 or 2 components, and the group with ≥3 components. CONCLUSIONS: The current study found that there was no statistically significant association between metabolic syndrome and prostate cancer development in a Korean population. However, results of this study should be interpreted with consideration due to several limitations including the diversity of definitions of metabolic syndrome components.

How Much Reliable Is the Current Belief on Grade Group 1 Prostate Cancer?

Objective: To evaluate the clinicopathological characteristics of grade group 1 (GG1) prostate cancer in Korean populations. Methods: We retrospectively analyzed 492 consecutive radical prostatectomy specimens from our institution, which included those from 322 men with clinical GG1 and 170 with clinical GG2 tumors between years 2009 and 2018. The incidence of Gleason score (GS) upgrading, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) were evaluated in patients with clinical GG1. In pathological GG1 cases, the distribution of adverse pathological features including EPE, lymphovascular invasion (LVI), perineural invasion (PNI), and biochemical recurrence (BCR) was analyzed. Results: Altogether, 78 (24.2%) out of 322 men in the clinical GG1 group demonstrated upgrading of GS, including 19 men with pathological Gleason score 4 + 3 = 7 and 6 with ≥ pathological Gleason score 4 + 4 = 8 cases. EPE was found in 37 (11.5%) and 22 (8.9%) men in clinical GG1 and pathological GG1 group, respectively. The incidence of LVI and PNI in the pathological GG1 cases was 2.8% (n = 7) and 28.6% (n = 71), respectively. BCR was observed in 4 men in pathological GG1 T2 (n = 226) and 2 men in GG1 T3 (n = 22) group. When we compared the pathological features between pathological GG1 T3 vs. GG2 T2, there was no statistical differences in the incidence of LVI and PNI between the two groups. Conclusions: Contrary to the current concept that GG1 is almost always clinically insignificant, it seems that GG1 still possess its respectable position as a group of cancer with aggressiveness. These findings should be kept in mind when deciding on treatment options for prostate cancer patients in the Asian populations.

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.

Predicting Insignificant Prostate Cancer: Analysis of the Pathological Outcomes of Candidates for Active Surveillance according to the Pre-International Society of Urological Pathology (Pre-ISUP) 2014 Era Versus the Post-ISUP2014 Era.

PURPOSE: To analyze the difference in the prediction accuracy with an active surveillance (AS) protocol between two eras (pre-International Society of Urological Pathology [pre-ISUP]-2014 vs. post-ISUP2014). MATERIALS AND METHODS: We retrospectively analyzed 118 candidates for AS who underwent radical prostatectomy between 2009 and 2017. We divided our patients into two groups (group 1 [n=57], operation date 2009-2015; group 2 [n=61], operation date 2016-2017). Pathologic slides in group 1 were reviewed to distinguish men with cribriform pattern (CP) because the determination of Gleason scores in old era had been based on pre-ISUP2014 classification. Postoperative outcomes in the two eras were analyzed twice: first, all men in group 1 vs. group 2; second, the remaining men after excluding those with CPs in group 1 vs. group 2. RESULTS: The proportion of men with insignificant prostate cancer (iPCa) was significantly lower in group 1 than in group 2 (36.8% vs. 57.4%, p=0.040). After excluding 11 men with CPs from group 1, those remaining (46 men) were compared again with group 2. In this analysis, the proportion of men with iPCa was similar between the two groups (old vs. contemporary era: 41.3% vs. 57.4%, p=0.146). Nine of 11 men with CP had violated the criteria for iPCa in the earlier comparison. CONCLUSIONS: The accuracy of the AS protocol has been affected by the coexistence of CPs and pure Gleason 6 tumors in the pre-ISUP2014 era. We suggest to use only contemporary (post-ISUP2014) data to analyze the accuracy with AS protocols in future studies.

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.

Association between the neutrophil-to-lymphocyte ratio and intravesical prostatic protrusion in men with benign prostatic hyperplasia.

OBJECTIVE: To analyze the association between neutrophil-to-lymphocyte ratio (NLR) and intravesical prostatic protrusion (IPP) in men with benign prostatic hyperplasia. METHODS: Two hundred and fifty men aged >50 years who presented with lower urinary tract symptoms at our institution between 2014 and 2018 were analyzed. Pearson's method was used for analysis of the correlation between NLR and IPP. Multivariate logistic regression analysis was used to identify predictors of IPP. Further analysis according to total prostate volume (TPV) was performed. RESULTS: The NLR correlated positively with IPP (Pearson's r = 0.459, P < 0.001) and was an independent predictor of IPP ≥10 mm (odds ratio, 2.95; 95% confidence interval, 1.59-5.47; P = 0.0006). Among the 142 men with prostates <40 cm3 , mean NLR was 2.50 ± 0.71 in those with IPP ≥10 mm and 1.71 ± 0.57 in those with IPP < 10 mm (P < 0.001). The NLR differed significantly between those with a prostate <40 cm3 and IPP ≥10 mm and those with a larger prostate and IPP < 10 mm (2.50 ± 0.71 vs 2.07 ± 0.77, respectively; P = 0.020). CONCLUSIONS: NLR can be used as a surrogate marker for presence of IPP. Its clinical value would be especially important in men with a small prostate gland but high IPP. The NLR seemed to be more strongly correlated with IPP than with TPV.

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.

Clinical Outcomes and Factors Influencing These Outcome Measures Resulting in Success After Arthroscopic Transosseous Triangular Fibrocartilage Complex Foveal Repair.

PURPOSE: To analyze postoperative outcomes after arthroscopic transosseous triangular fibrocartilage complex (TFCC) foveal repair and identify factors affecting the clinical outcomes. METHODS: This study retrospectively enrolled patients who were treated for TFCC foveal tears by arthroscopic transosseous TFCC foveal repair. The diagnosis of TFCC foveal tear was made based on medical history, physical examination, and magnetic resonance imaging, with confirmation via arthroscopic examination. Outcome evaluation was completed at a minimum of 2 years postoperatively, and patients were classified into 2 groups according to the minimal clinically important difference of the Patient-Rated Wrist Evaluation. Various factors including age, sex, trauma history, body mass index, symptom duration, hand dominance, ulnar variance, subluxation of the distal radioulnar joint, preoperative pain score, and functional status, as well as the cross-sectional area (CSA) of the pronator quadratus (PQ) muscle, were retrospectively analyzed using both univariate and multivariate analyses. RESULTS: During the study period, 42 patients were treated for TFCC foveal tears. The functional status significantly improved after surgery. Overall, 27 and 15 patients showed good and poor functional outcomes, respectively, which were assessed according to the minimal clinically important difference of the Patient-Rated Wrist Evaluation. On univariate analysis, clinical outcomes were better in male patients (P = .035), younger patients (P = .022), and those with higher CSAs of the PQ muscles (P < .001). However, on multivariable logistic regression analysis, only a higher CSA of the PQ muscle was identified as an independent prognostic factor affecting clinical outcome after TFCC foveal repair (P = .004). CONCLUSION: Arthroscopic transosseous TFCC complex foveal repair led to satisfactory results. However, lower PQ muscle CSA on magnetic resonance imaging was the most independent prognostic factor negatively affecting clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

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.

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.

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.

Suppression of Oxidative Stress of Modified Gongjin-Dan (WSY-1075) in Detrusor Underactivity Rat Model Bladder Outlet Induced by Obstruction.

OBJECTIVE: To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model. METHODS: Rats were randomly allocated to three groups: shamoperated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders. RESULTS: Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05). CONCLUSION: WSY-1075 had beneficial effect on prevention of BOO-DU.

Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo.

Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model. Intranasal administration of gemcitabine significantly lowered pulmonary viral load and inflammation by decreasing proinflammatory cytokines, including TNF-α and IL-1ß, and reduction in the number of lung-infiltrating lymphocytes. Interestingly, we found that the addition of UTP and CTP significantly attenuated the antiviral activity of gemcitabine. Thus the limitation of UTP and CTP by the addition of gemcitabine may inhibit the viral RNA synthesis. These results suggest that gemcitabine, an antineoplastic drug, can be repositioned as an antiviral drug to inhibit HRV infection.

Mineralized deposits in the uterus of a pig without pregnancy loss.

Herein, we describe a case of uterine calcification in the uterus of a pig without pregnancy loss. The recipient underwent cloned embryo transfer and Cesarean section for safe delivery of cloned piglets. During the Cesarean section, 4 white, star-like, (2 × 2 × 2) cm, calcified structures were found within the endometrial cavity. Despite dystrophic calcification around the placenta, healthy cloned piglets were produced successfully. To our knowledge, this is the first reported case of dystrophic calcification occurring within the uterus in a pregnant pig.