• Journal of Ginseng Research
• /
• v.43 no.4
• /
• pp.562-571
• /
• 2019

Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.1
• /
• pp.30-36
• /
• 2019

Numerous studies have reported that enteric neurons involved in controlling neurotransmitter secretion and motility in the gut critically contribute to the progression of gut inflammation. Clostridium difficile toxins, which cause severe colonic inflammation, are also known to affect enteric neurons. Our previous study showed that C. difficile toxin A directly induces neural cell toxicities, such as viability loss and apoptosis. In the current study, we attempted to identify a potent inhibitor of toxin A-induced neural cell toxicity that may aid in managing toxin A-induced gut inflammation. In our recent study, we found that the Korea dung beetle-derived antimicrobial peptide CopA3 completely blocked neural cell apoptosis caused by okadaic acid or 6-OHDA. Here, we examined whether the antimicrobial peptide CopA3 inhibited toxin A-induced neural cell damage. In neuroblastoma SH-SY5Y cells, CopA3 treatment protected against both apoptosis and viability loss caused by toxin A. CopA3 also completely inhibited activation of the pro-apoptotic factor, caspase-3. Additionally, CopA3 rescued toxin A-induced downregulation of neural cell proliferation. However, CopA3 had no effect on signaling through ROS/p38 $MAPK/p27^{kip1}$, suggesting that CopA3 inhibits toxin A-induced neural cell toxicity independent of this well-characterized toxin A pathway. Our data further suggest that ability of CopA3 to rescue toxin A-induced neural cell damage may also ameliorate the gut inflammation caused by toxin A.

• Journal of Applied Biological Chemistry
• /
• v.62 no.1
• /
• pp.19-23
• /
• 2019

The chemical compositions of the essential oil of Valeriana officinalis roots obtained by steam distillation method were analyzed by GC-MS. The 16 constituents were identified in the V. officinalis oil, and the most abundant compounds were patchouli alcohol (18.69%) and ${\beta}$-gurjunene (15.26%). Acaricidal effects of the V. officinalis oil were evaluated against Tyrophagus putrescentiae, Haemaphysalis longicornis larva and H. longicornis nymph by contact bioassay. The $LD_{50}$ values against T. putrescentiae, H. longicornis larva and H. longicornis nymph were 28.01, 178.26 and $207.98{\mu}g/cm^2$, respectively. Agar disc diffusion bioassay showed the antibacterial activity of the V. officinalis oil against foodborne pathogens, especially L. monocytogenes. These results showed that the essential oil of V. officinalis roots derived from USA has a potential for development as acaricide and antimicrobial.

• Journal of Gynecologic Oncology
• /
• v.29 no.6
• /
• pp.97.1-97.12
• /
• 2018

Objective: Women with cervical cancer (CC) found to have positive surgical margins, positive lymph nodes, and/or parametrial invasion receive a survival benefit from postoperative chemoradiotherapy (CRT) vs. radiation therapy (RT) alone. However, older women may not benefit to the same extent, as they are at increased risk of death from non-oncologic causes as well as toxicities from oncologic treatments. This study sought to evaluate whether there was a survival benefit of CRT over RT in elderly patients with cervical cancer. Methods: The National Cancer Database was queried for patients ${\geq}70$ years old with newly diagnosed IA2, IB, or IIA CC and positive margins, parametrial invasion, and/or positive nodes on surgical resection. Statistics included logistic regression, Kaplan-Meier overall survival (OS), and Cox proportional hazards modeling analyses. Results: Altogether, 166 patients met inclusion criteria; 62 (37%) underwent postoperative RT and 104 (63%) underwent postoperative CRT. Younger patients and those living in areas of higher income were less likely to receive CRT, while parametrial invasion and nodal involvement were associated with an increased likelihood (p<0.05 for all). There were no OS differences by treatment type. Subgroup analysis by number of risk factors, as well as each of the 3 risk factors separately, also did not reveal any OS differences between cohorts. Conclusion: In the largest such study to date, older women with postoperative risk factor(s) receiving RT alone experienced similar survival as those undergoing CRT. Although causation is not implied, careful patient selection is paramount to balance treatment-related toxicity risks with theoretical outcome benefits.

• Journal of Gastric Cancer
• /
• v.20 no.4
• /
• pp.395-407
• /
• 2020

Purpose: A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer. Materials and Methods: A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality. Results: All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%-72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%-85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%-89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%-82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24-31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%-66.1%). Conclusions: Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment.

• Biomolecules & Therapeutics
• /
• v.29 no.4
• /
• pp.399-409
• /
• 2021

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

• Journal of the Korean Society of Marine Environment & Safety
• /
• v.27 no.1
• /
• pp.119-126
• /
• 2021

In this study, the variability in paralytic shellfish poisoning (PSP) by the toxic dinoflagellate Alexandrium catenella (Group I) was analyzed under a variety of water temperatures and salinities. This dinoflagellate experienced optimum growth at temperatures and salinities of 20~30℃ and 20~30 psu, respectively. These findings indicate that A. catenella is an eurythermal and euryhaline organism. High toxin contents and toxicities were observed at low temperatures (10 and 15℃), where they were associated with low growth rates; salinity did not have any significant impact on toxicity parameters. Therefore, it is likely that A. catenaella contributes to the rapid intoxication of commercial bivalve when temperatures are ≤15℃. To better estimate PSP caused by A. catenalla, we suggest that the influence of various environmental factors controlling PSP should persist with other A. catenella stains and commercial bivalves.

• Journal of Dental Anesthesia and Pain Medicine
• /
• v.21 no.2
• /
• pp.113-118
• /
• 2021

Background: Consumers and patients in the last two decades have increasingly turned to various internet search engines including Google for information. Google Trends records searches done using the Google search engine. Google Trends is free and provides data on search terms and related queries. One recent study found a large public interest in "dental anesthesia". In this paper, we further explore this interest in "dental anesthesia" and assess if any patterns emerge. Methods: In this study, Google Trends and the search term "dental pain" was used to record the consumer's interest over a five-year period. Additionally, using the search term "Dental anesthesia," a top ten related query list was generated. Queries are grouped into two sections, a "top" category and a "rising" category. We then added additional search term such as: wisdom tooth anesthesia, wisdom tooth general anesthesia, dental anesthetics, local anesthetic, dental numbing, anesthesia dentist, and dental pain. From the related queries generated from each search term, repeated themes were grouped together and ranked according to the total sum of their relative search frequency (RSF) values. Results: Over the five-year time period, Google Trends data show that there was a 1.5% increase in the search term "dental pain". Results of the related queries for dental anesthesia show that there seems to be a large public interest in how long local anesthetics last (Total RSF = 231) - even more so than potential side effects or toxicities (Total RSF = 83). Conclusion: Based on these results it is recommended that clinicians clearly advice their patients on how long local anesthetics last to better manage patient expectations.

• Journal of Marine Bioscience and Biotechnology
• /
• v.12 no.2
• /
• pp.108-114
• /
• 2020

A variety of shellfish species sold for human consumption are available for purchase in the domestic fish market. The microalgae families inhabit the ocean, where planktons supply the main nutritional resource for the growth of shellfish. Some phytoplanktons produce toxic compounds that are accumulated in shellfish and ultimately cause toxicity in humans. This article reports the cytotoxicity of commercially available shellfish species. Accordingly, hot water extract (HWE) and an aqueous fraction of 50% methanol extract (MEE-AF) showed no significant cytotoxicity on the two cell lines (i.e., HL-60 and Vero cell lines), but 50% methanol extract (MEE) in 3, 6 samples showed 50% cytotoxic effects on HL-60 cells, and 1, 4 samples showed 40%, 20% cytotoxic effects on Vero cells, respectively. In addition, their consequential dichloromethane fractions (MEE-DF) exhibited significant toxicities at the highest concentration (1,000 ㎍/ml) on HL-60 and Vero cells. Since the shellfish samples showed cytotoxicity in the dichloromethane fraction, it is possible that the dichloromethane fraction contains marine toxins. Further research will be needed to identify the toxic components from each sample.

• Journal of The Korean Society of Clinical Toxicology
• /
• v.19 no.2
• /
• pp.133-138
• /
• 2021

Glufosinate-containing herbicides is a non-selective herbicide commonly used worldwide. As the use of them increased gradually since paraquat was banned in 2012, the number of suicides by their ingestion is also increasing continuously. Complications of glufosinate-containing herbicide poisoning include various central nervous system (CNS) toxicities such as convulsions, loss of consciousness, memory impairment, and respiratory depression, which may be accompanied by hemodynamic changes such as bradycardia and hypotension. However, it is very rare that arrhythmias other than bradycardia occurred and Takotsubo cardiomyopathy was combined due to cardiotoxicity. A 71-year-old female patient was transferred to our hospital after ingesting 500 mL of glufosinate-containing herbicide and receiving 5 L of gastric lavage at a local hospital. A few hours later, she presented stuporous mentality, respiratory depression, and convulsions, and was accompanied by hypotension and bradycardia. On the second day of admission, electrocardiogram (ECG) showed bradycardia and QTc prolongation with hemodynamic Instability. Accordingly, we conducted the early treatment with continuous renal replacement therapy (CRRT) and the application of temporary cardiac pacemaker. An echocardiogram demonstrated decreased ejection fraction (EF) and Takotsubo cardiomyopathy on the third day of admission. Then, she was discharged safely with conservative treatment. At the follow-up after 1 year, Takotsubo cardiomyopathy, EF and QTc prolongation were recovered on echocardiogram and ECG. Because cardiac toxicity after glufosinate-containing herbicide poisoning may cause life-threatening consequences, caution is required while treating the patient. Therefore, if electrocardiogram changes are seen in the elderly with a large amount of glufosinate herbicide ingestion, additional cardiac function test through echocardiography should be concerned, and early treatment through CRRT or artificial cardiac pacing should be considered.