Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

Substance P and beta-endorphin mediate electro-acupuncture induced analgesia in mouse cancer pain model

<p>Abstract</p> <p>Background</p> <p>Opioid analgesics are generally used to combat the pain associated with cancerous conditions. These agents not only inhibit respiratory function and cause constipation, but also induce other significant side effects such as addiction and tolerance, all of which further contribute to a reduced quality of life for cancer patients. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in a cancer pain mouse model.</p> <p>Methods</p> <p>In order to produce a neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. Magnetic Resonance Imaging (MRI) scanning confirmed the mass of S-180 cancer cells embedded around the sciatic nerve. Mechanical allodynia was most consistently induced in the mouse sarcoma cell line S-180 (2 × 10⁶sarcoma cells)-treated group compared to all the other groups studied. EA stimulation (2 Hz) was administered daily to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation.</p> <p>Results</p> <p>EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation. It also shortened the cumulative lifting duration from 7 days after inoculation, compared to the tumor control. Also, the overexpression of pain peptide substance P in the dorsal horn of the spinal cord was significantly decreased in the EA-treated group compared to the tumor control on Day 9 post inoculation. Furthermore, EA treatment effectively increased the concentration of β-endorphin in blood and brain samples of the mice to a greater extent than that of the tumor control as well as the normal group. The concentration of β-endorphin for EA treatment group increased by 51.457% in the blood and 12.6% in the brain respectively, compared to the tumor control group.</p> <p>Conclusion</p> <p>The findings of this study suggest that a S-180 cancer pain model is useful as a consistent and short time animal model. It also indicated that EA treatment could be used as an alternative therapeutic method for cancer pain due to a consequent decrease in substance P and increase in β-endorphin levels.</p

Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Objective: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration.&nbsp;Methodology: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination.&nbsp;Results: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the ca p. Conclusion: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation

Epileptic nystagmus: A case report and systematic review

AbstractPurposeWe aimed to define the characteristics of epileptic nystagmus and correlate those with other clinical findings in a large number of patients.MethodsWe report a patient with epileptic nystagmus and additionally reviewed the reported clinical features of 36 more patients through a systematic literature search. We analyzed the characteristics of epileptic nystagmus and attempted correlations of those with alertness of the patients and epileptic foci on EEG.ResultsAll 33 patients with unilateral horizontal nystagmus showed nystagmus beating away from the side of ictal discharges. Epileptic nystagmus was preceded by gaze deviation in 21 patients, with contraversive in 19 and ipsiversive in 2. Seizures associated with epileptic nystagmus were mostly focal (25/29, 86.2%) with or without loss of awareness. Ictal discharges originated from the occipital (n=16), parietal (n=9), temporo-occipital (n=6), frontal (n=4), and temporal (n=3) areas, and two patients had multiple epileptic foci. Seizures were usually symptomatic (24/37, 64.9%). The presence of preceding gaze deviation and midline crossing of the nystagmus did not correlate with the ictal onset zone or alertness of the patients. Recording of epileptic nystagmus was available only in 6 patients, and the epileptic nystagmus could be localized to the saccadic areas in two and to the smooth pursuit areas in another two. Two patients showed the features of epileptic nystagmus from both areas.ConclusionEven though the localizing value of epileptic nystagmus seems limited in previous reports, the fast phase of epileptic nystagmus was almost always directed away from the epileptic focus that mostly arose from the posterior part of the cerebral hemisphere

A Toxicological Study of HangAmDan-B in Mice

AbstractThe aim of the study was to define the toxicity of HangAmDan-B (HAD-B) in mice over the short and long term. HAD-B was studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. Doses used in 1 week single oral dose toxicity tests were 0, 0.2, 1, 5, and 25 g/kg/day and those of repeated toxicity test were 0, 0.04, 0.2, 1, and 2 g/kg/day. Blood and urine samples were assayed and their morphology observed. Numerical data were compared using Mann-Whitney U test and analysis of variance. Significantly decreased red blood cell levels in mice from S2-HAD-B, S3-HAD-B, S4-HAD-B, and S5-HAD-B groups were observed in single oral dose toxicity tests. Hemoglobin, hematocrit, and mean cell hemoglobin values in mice from the S4-HAD-B and S5-HAD-B groups were also significantly decreased. No mortalities or significant differences in all factors were observed during the dosing period of the repeated dose toxicity test. Administering 2 g/kg/day of HAD-B in mice over a 5-week period showed no significant hematological changes. However, risk of anemia with more than 5 g/kg/ day administration of HAD-B was found. In general, HAD-B appears to be safe and nontoxic, and a no observed adverse effect level in mice was established at 2 g/kg/ day. This data serves as satisfactory preclinical evidence for the safety of HAD-B should a future clinical trial for HAD-B be launched. Further studies are required to confirm these safety results and to carry out a safety trial in humans