Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells.

Oxidative stress and inflammatory responses have been identified as key elements of neuronal cell apoptosis. In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in human neuroblastoma SH-SY5Y cells treated with fipronil (FPN). Based on the cytotoxic mechanism of FPN, we examined the neuroprotective effects of meloxicam against FPN-induced neuronal cell death. Treatment of SH-SY5Y cells with FPN induced apoptosis via activation of caspase-9 and -3, leading to nuclear condensation. In addition, FPN induced oxidative stress and increased expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) via inflammatory stimulation. Pretreatment of cells with meloxicam enhanced the viability of FPN-exposed cells through attenuation of oxidative stress and inflammatory response. FPN activated mitogen activated protein kinase (MAPK) and inhibitors of MAPK abolished FPN-induced COX-2 expression. Meloxicam also attenuated FPN-induced cell death by reducing MAPK-mediated pro-inflammatory factors. Furthermore, we observed both nuclear accumulation of p53 and enhanced levels of cytosolic p53 in a concentration-dependent manner after FPN treatment. Pretreatment of cells with meloxicam blocked the translocation of p53 from the cytosol to the nucleus. Together, these data suggest that meloxicam may exert anti-apoptotic effects against FPN-induced cytotoxicity by both attenuating oxidative stress and inhibiting the inflammatory cascade via inactivation of MAPK and p53 signaling.

Parents' beliefs and intentions toward supporting physical activity participation for their children with disabilities.

The purpose of this study was to examine validity and reliability evidence of a questionnaire regarding parents' beliefs and intentions toward supporting physical activity (PA) participation of their children with disabilities (CWD). A total of 220 parents of CWD in South Korea completed a questionnaire that was developed using the theory of planned behavior (TPB). Exploratory factor analysis revealed that behavioral, control, and normative beliefs accounted for 31.13%, 20.45%, and 19.63% of the total variance of the intention, respectively. Reliability of entire scale was .85 using Cronbach's alpha. Reliabilities of the 3 beliefs were .86, .82, and .87, respectively. Standard multiple-regression analysis indicated that behavioral and normative beliefs significantly predicted parents' intention, p < .01. Intention was a significant predictor of parents' behavior, p < .01. The results of this study indicated that the TPB can be useful to examine parental support for PA participation of their CWD.

An outbreak of food borne illness due to methomyl pesticide intoxication in Korea.

On February 21, 2013, 6 elderly people collapsed abruptly after eating bean sprout bibimbab (boiled rice mixed with bean sprouts and seasoned with soybean sauce) at a countryside restaurant in the Chungbuk Province, Korea. Minutes after eating the meal, all of the patients lapsed into a state of stupor. Respiratory arrest developed in 2 patients; and one of two patients died of cardiac arrest. The autopsy identified methomyl and methanol in the deceased patient's gastric contents and in the remaining soybeanbean sauce seasoning. Five of the 6 patients ingested one spoonful of the soybeanbean sauce seasoning and survived, while one patient who died of cardiac arrest, ingested approximately two spoons. Symptoms of toxicity presented quickly in the subjects and progressed rapidly, including chest tightness, an unusual sensation in the pit of the stomach, dizziness, ataxia, and finally, collapse. Three patients who drank ethanol with the meal experienced only mild toxic symptoms. Our analysis of the clinical observations in these cases suggests that ingestion of methomyl pesticide and the additive toxicity of methanol may have been responsible for the intoxication.

A case of acute prochloraz-manganese complex intoxication treated with extracorporeal elimination.

BACKGROUND/AIM: We treated a patient with critical manganese intoxication with vigorous extracorporeal elimination. In this article, we describe the clinical characteristics and treatment modalities of the patient. PATIENT: A 65-year-old man was brought to the emergency room (ER) 5.5 h after ingesting prochloraz-manganese complex. He experienced circulatory collapse and went into a coma without self-breathing on arrival at the ER. Mechanical ventilation was initiated and hemoperfusion, hemodialysis and continuous venovenous hemodiafiltration were performed with the help of norepinephrine. MEASUREMENT AND RESULT: The manganese levels on the first, second and fourth hospital days were 34.1, 23.6 and 12.5 µg/l, respectively. He recuperated from the shock state within 7 hospital days. After 4 critical weeks, the patient regained full consciousness. CONCLUSION: Rigorous extracorporeal elimination by hemoperfusion, hemodialysis and continuous venovenous hemodiafiltration was an effective treatment modality for patients with acute manganese intoxication.

Species Composition, Abundance, and Seasonal Dynamics of Perilla Seed Bugs (Heteroptera: Lygaeidae) in Weeds and Perilla Fields in Korea.

Perilla seed bugs (Nysius sp.) are considered to be the emerging pests causing nutritional and yield losses in perilla and cereal crops. A survey of perilla seed bugs on weeds and perilla crops was conducted over the course of 2 yr in Korea to determine the species composition, abundance, and seasonal dynamics of perilla seed bugs. Three species of Heteroptera (Nysius plebeius, Nysius hidakai, and Nysius inconspicuus), nymphs of Nysius species, and several parasitoid species were collected from weeds and perilla crops. Nysius hidakai was the most abundant perilla seed bugs. In 2019, adult perilla seed bugs, nymphs of perilla seed bugs, and parasitoid species were more abundant in weed species than in perilla crops. An early peak with a greater number of adult perilla seed bug (N. hidakai) was observed in weeds in 2020. However, an identical peak with a similar number of perilla seed bug (N. hidakai) was found in perilla crops in both years. Peak perilla seed bugs densities were observed in the 4th week of June, 2020 in weeds. Parasitoid species from Aphidiidae (1), Braconidae (11), Eulophidae (7), Figitidae (5), Ichneumonidae (7), Platygastridae (1), and Pteromalidae (5) subfamilies were collected. Perilla seed bugs seem to be a serious and increasingly important pest in several field crop species including perilla crops grown on the southern Korean peninsula. Monitoring and early detection of insect species are vital to predicting seasonal colonization and population build-up of perilla seed bugs on perilla crops from a climate change perspective, and essential for developing appropriate management techniques. Thus, continuous monitoring of perilla seed bugs in alternative weed hosts is needed to protect perilla crops from perilla seed bug infestation.

Effects of lifestyle modifications on C-reactive protein: contribution of weight loss and improved aerobic capacity.

High-sensitivity C-reactive protein (hs-CRP) is associated with an increased risk of cardiovascular disease and the development of type 2 diabetes mellitus. We analyzed the effects of lifestyle modifications including exercise training on hs-CRP in 47 overweight and obese adults. Subjects were divided into a lifestyle modification group (n=23) (exercise and diet instruction) and a control group (n=24) who did not participate in any lifestyle modification. After 3 months, body weight (80.8+/-11.5 to 73.5+/-10.7 kg, P<.01), total cholesterol (217+/-38.4 to 178.0+/-25.6 mg/dL, P<.01), low-density lipoprotein cholesterol (151.3+/-34.9 to 116.7+/-27.8 mg/dL, P<.01), Vo(2)peak (30.3+/-5.1 to 37.1+/-6.9 mL/[kg . min], P<.01), and log hs-CRP (0.75+/-0.4 to 0.56+/-0.3 mg/dL, P=.01) were significantly improved in the lifestyle modification group, but there was no significant improvement in the control group. Changes in log hs-CRP were associated with changes in Vo(2)peak (r=-0.41, P=.004) and changes in weight loss (r=0.42, P=.004). In stepwise multiple regression analysis, weight loss (P=.034) and improved Vo(2)peak (P=.039) were independent predictors of the changes in hs-CRP. When grouped into quartiles according to decreasing weight and increasing Vo(2)peak, levels of changes in log hs-CRP improved across quartiles of weight loss (P<.05) and improved Vo(2)peak (P<.01). Thus, lifestyle changes including regular exercise training in overweight and obese adults decreased hs-CRP, and this was associated with weight loss and improved Vo(2)peak.

Pulmonary Proteome and Protein Networks in Response to the Herbicide Paraquat in Rats.

Paraquat (PQ) has been one of the most widely used herbicides in the world. PQ, when ingested, is toxic to humans and may cause acute respiratory distress syndrome. To investigate molecular perturbation in lung tissues caused by PQ, Sprague Dawley male rats were fed with PQ at a dose of 25 mg/kg body weight for 20 times in four weeks. The effects of PQ on cellular processes and biological pathways were investigated by analyzing proteome in the lung tissues in comparison with the control. Among the detected proteins, 321 and 254 proteins were over-represented and under-represented, respectively, in the PQ-exposed rat lung tissues in comparison with the no PQ control. All over- and under-represented proteins were subjected to Ingenuity Pathway Analysis to create 25 biological networks and 38 pathways of interacting protein clusters. Over-represented proteins were involved in the C-jun-amino-terminal kinase pathway, caveolae-mediated endocytosis signaling, cardiovascular-cancer-respiratory pathway, regulation of clathrin-mediated endocytosis, non-small cell lung cancer signaling, pulmonary hypertension, glutamate receptor, immune response and angiogenesis. Under-represented proteins occurred in the p53 signaling pathway, mitogen-activated protein kinase signaling pathway, cartilage development and angiogenesis inhibition in the PQ-treated lungs. The results suggest that PQ may generate reactive oxygen species, impair the MAPK/p53 signaling pathway, activate angiogenesis and depress apoptosis in the lungs.

Health status and related factors in farmers by SF-12.

OBJECTIVES: This study was performed to understand farmers' health status by general characteristic, and to find out the related factors. METHODS: All the 984 subjects were interviewed by means of a structured questionnaire and SF-12. Among them, only 812 were eligible for analysis. Statistical methods used included frequency, t-test, ANOVA, binary logistic regression with SPSS 19.0. RESULTS: In binary logistic regression, marital status, smoking, regular exercise and monthly day off were associated with physical component score. Marital status, smoking and score of pesticide protective device wearing were associated with mental component score. CONCLUSIONS: This study suggests that effort to develop health promotion programs for workers of agricultural industry considering these results can improve their perceived health status.

Agricultural pesticide usage and prioritization in South Korea.

This study aims to review agricultural pesticide usage and trends and to identify hazardous pesticides for regulation, in terms of public health, in South Korea. The authors collected data on usage and trends of agricultural pesticides through agriculture-related databases. Criteria from the US Environmental Protection Agency classification for carcinogenicity, World Health Organization classification for acute toxicity, and European Union prioritization list for endocrine-disrupting chemicals were used for the hazard categorization of identified individual active ingredients. Pesticides to be prioritized among all pesticides used in South Korea between 2007 and 2011 were selected by taking into account the volume of usage, toxicity, and epidemiological evidence. Annual agricultural use of pesticides has increased rapidly from the 1970s to 1990s in South Korea, but has declined since 2001. The quantity of pesticides used in 2011 was reported as 19,131 tons, and was comprised of 34.7% insecticides, 28.0% fungicides, and 27.1% herbicides. The 50 pesticides with the greatest volume of usage accounted for 82.6% of the total volume of pesticides used between 2007 and 2011, with the most-used active ingredient being machine oil, followed by mancozeb and then paraquat. Organophosphates were the most used among the top 50 pesticides. A total of 24 pesticides were selected for recommendation of intensive regulation in South Korea. In conclusion, the authors described the usage and trends of overall agricultural pesticides, which would serve as a fundamental step forward in managing pesticide in terms of public health. Intensive efforts are required for the prevention of potential health effects from the 24 identified pesticides.

Comparison of international guidelines of dermal absorption tests used in pesticides exposure assessment for operators.

The number of farmers who have suffered from non-fatal acute pesticide poisoning has been reported to vary from 5.7% to 86.7% in South Korea since 1975. Absorption through the skin is the main route of exposure to pesticides for farmers who operate with them. Several in vitro tests using the skins of humans or animal and in vivo tests using laboratory animals are introduced for the assessment of human dermal absorption level of pesticides. The objective of this study is to evaluate and compare international guidelines and strategies of dermal absorption assessments and to propose unique approaches for applications into pesticide registration process in our situation. Until present in our situation, pesticide exposure level to operator is determined just using default value of 10 as for skin absorption ratio because of data shortage. Dermal absorption tests are requested to get exposure level of pesticides and to ultimately know the safety of pesticides for operators through the comparison with the value of AOEL. When the exposure level is higher than AOEL, the pesticide cannot be approved. We reviewed the skin absorption test guidelines recommended by OECD, EFSA and EPA. The EPA recommends assessment of skin absorption of pesticides for humans through the TPA which includes all the results of in vitro human and animal and animal in vivo skin absorption studies. OECD and EFSA, employ a tiered approach, which the requirement of further study depends on the results of the former stage study. OECD guidelines accept the analysis of pesticide level absorbed through skin without radioisotope when the recovery using the non-labeled method is within 80~120%. Various factors are reviewed in this study, including the origin of skin (gender, animal species and sites of skin), thickness, temperature and, etc., which can influence the integrity of results.

Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells.

Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy.

Change in kidney damage biomarkers after 13 weeks of exposing rats to the complex of Paecilomyces sinclairii and its host Bombyx mori larvae.

Complex of Paecilomyces sinclairii and host larvae, Bombyx mori, is a well known health food; however, concerns about nephrotoxicity have been raised. Kidney toxicity was investigated after 13 weeks of administering the complex orally to rats with parameters including blood urea nitrogen (BUN), creatinine, and kidney damage biomarkers, beta-2-microglobulin (ß2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin. Dose-dependent kidney cell karyomegaly and tubular hypertrophy were observed, with higher severity in males. There was a dose-dependent increase in KIM-1 and TIMP-1 levels in kidney and urinary KIM-1, cystatin C, ß2m, and osteopontin levels. KIM-1 and TIMP-1 increased in male kidneys had not recovered by 2 weeks after stopping exposure. Cystatin C in kidney was significantly lowered in all treatment groups at 13 weeks of administration. All the changes were more noticeable in males. These data indicate that the complex damage renal tubule cells with histopathological lesions and changes in biomarker levels. Kidney and urinary KIM-1 and cystatin C were the most markedly affected and early increased indicators among biomarkers tested, whereas BUN and creatinine were not affected.

Antimicrobial activity of the synthetic peptide scolopendrasin ii from the centipede Scolopendra subspinipes mutilans.

The centipede Scolopendra subpinipes mutilans is a medicinally important arthropod species. However, its transcriptome is not currently available and transcriptome analysis would be useful in providing insight into a molecular level approach. Hence, we performed de novo RNA sequencing of S. subpinipes mutilans using next-generation sequencing. We generated a novel peptide (scolopendrasin II) based on a SVM algorithm, and biochemically evaluated the in vitro antimicrobial activity of scolopendrasin II against various microbes. Scolopendrasin II showed antibacterial activities against gram-positive and -negative bacterial strains, including the yeast Candida albicans and antibiotic-resistant gram-negative bacteria, as determined by a radial diffusion assay and colony count assay without hemolytic activity. In addition, we confirmed that scolopendrasin II bound to the surface of bacteria through a specific interaction with lipoteichoic acid and a lipopolysaccharide, which was one of the bacterial cell-wall components. In conclusion, our results suggest that scolopendrasin II may be useful for developing peptide antibiotics.

Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces sinclairii in Rats.

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (ß2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

Physical education teachers' beliefs and intentions toward teaching students with disabilities.

The Theory of Planned Behavior (TpB) measures the effect that individuals' behavioral belief normative belief and control beliefs have on their intentions to perform a specific behavior The purpose of this study was to examine: (a) whether the TpB could predict physical educators' intentions and (b) whether physical educators' intentions and control beliefs could predict their self-reported teaching behavior. A sample of 220 physical educators completed the questionnaire. Stepwise multiple regression analysis revealed that the TpB significantly predicted physical educators' intentions, F(3, 216) = 57.21, p < .01. However, only intention was a significant predictor of physical educators'self-reported behavior in teaching students with disabilities, F(2, 123) = 34.04, p < .01.