Molecular Toxicology of Pyrrolizidine Alkaloids

Pyrrolizidine alkaloids are cytotoxic, carcinogenic, and anti-carcinogenic in vivo and in vitro, and they produce many hazardous effects in humans and animals. Pyrrolizidine alkaloids (PAs) also cross-link with DNA and/or protein. However, whether such cross-linking is important to the toxic action of PAs is not known. In addition, the exact mechanism underlying these DNA cross-links or cytotoxicity is also not clear. In three separate studies, I characterized the nature of PA-induced DNA cross-links and the relationships between PA structures and cross-linking potency. In the first study (Chapter II), I found that cross-linking potency of PA congeners coincided with their abilities to cause cytopathologic effects. Macrocyclic a,p-unsaturated diesters PAs and their pyrrolic metabolites were the most potent inhibitors of colony formation, and inducers of cytopathologic changes and megalocyte formation. The macrocyclic α, β-saturated diester PA and open diesters PAs slightly inhibited colony formation, and slightly changed cell morphology. Retronecine and indicine N-oxide were completely inactive. In the next study (Chapter Ill), I found that pyrrolic macrocyclic metabolites were more potent DNA cross-linkers than their parent compounds as determined by alkaline elution. The pyrroles of the macrocyclic diester PAs were potent DNADNA (inter- and/or intra) cross-linkers in BstEll-digested λ-phage DNA or pBR322 plasmid DNA but dehydroretronecine and indicine N-oxide were not. I also examined which DNA sequences were more susceptible to PA-induced cross-links by using a series of restriction endonucleases to determine sequence specificity. The most favorable cross-linking site for PAs appeared to be 5\u27d(GG) and 5\u27-d(GA) although other sites, 5\u27-d(CC) or 5\u27-d(CG), might be also preferable cross-linking targets. In the next study (Chapter IV), I characterized the nature of DNA-protein interactions induced by PAs, because I found in previous studies that PA-induced cross-links are largely protein associated. In PA or pyrrolic PA exposed cells, cross-linked proteins with molecular weights 40 - 60 kD were detected. Two-dimensional electrophoretic analysis revealed that these proteins were probably acidic in nature. In an in vitro system utilizing pBR322 or Bst Ell-digested λ-phage DNA. dehydrosenecionine induced DNAprotein cross-links with BSA, indicating that such interactions might be related to amino acid composition of protein. These results confirmed that PA-induced DNA cross-links (DNA-DNA, DNA-protein cross-links) are influenced by three structural features: the C1 ,2 unsaturation of pyrrolizidine ring, α, β-unsaturation, and size of the macrocyclic diester ring. The ability to form cross-links was closely related to the known toxic potencies of these PAs. From this research, I also conclude that DNA crosslinking is the most critical event leading to PA-related diseases and that crosslinking is due to pyrrolic metabolites of PAs, not via a common metabolite as was once thought

Symptom Bother, Physical and Mental Stress, and Health-related Quality of Life in Women with Overactive Bladder Syndrome

PURPOSE: The objective of this study was to identify the relationships among symptom bother, physical and mental stress and health-related quality of life (HRQoL) in women with overactive bladder (OAB) syndrome. METHODS: The participants were 106 women who were diagnosed with OAB (urgency, urge urinary incontinence, frequency, and/or nocturia) at P university hospital. Data were collected from Dec 23, 2011 to Aug 31, 2012. RESULTS: The mean score for symptom bother was 43.1 points, for physical stress, 12.8 which was slightly higher than mental stress (11.8), and for HRQoL, 63.9. For symptom type, there were statistically significant differences in the symptom bother (F=8.67, p<.001) and HRQL (F=3.32, p= .023). The Symptom bother of OAB was positively correlated with physical stress (r=.23, p= .014) and mental stress (r=.33, p<.001) and negatively correlated with the subscales of HRQoL; coping (r=-.66, p<.001), concern (r=-.71, p<.001), sleep (r=-.59, p<.001), and social interaction (r=-.58, p<.001). CONCLUSION: From the results, bother symptom was associated with physical, mental stress and HRQoL. These results suggest that nursing intervention programs for OAB should be developed not only to relieve the symptoms but also to reduce stress and improve the quality of life

Retina-Inspired Carbon Nitride-Based Photonic Synapses for Selective Detection of UV Light

Photonic synapses combine sensing and processing in a single device, so they are promising candidates to emulate visual perception of a biological retina. However, photonic synapses with wavelength selectivity, which is a key property for visual perception, have not been developed so far. Herein, organic photonic synapses that selectively detect UV rays and process various optical stimuli are presented. The photonic synapses use carbon nitride (C3N4) as an UV-responsive floating-gate layer in transistor geometry. C3N4 nanodots dominantly absorb UV light; this trait is the basis of UV selectivity in these photonic synapses. The presented devices consume only 18.06 fJ per synaptic event, which is comparable to the energy consumption of biological synapses. Furthermore, in situ modulation of exposure to UV light is demonstrated by integrating the devices with UV transmittance modulators. These smart systems can be further developed to combine detection and dose-calculation to determine how and when to decrease UV transmittance for preventive health care.

Association between shift work and obesity among female nurses: Korean Nurses’ Survey

Background: Shift work has been hypothesized as a risk factor for obesity. In this study, we investigated the association between current shift work and body mass index (BMI) among female nurses in Korea. The relationship between duration of shift work and BMI of the participants was also evaluated. Methods: This cross-sectional survey evaluated participants in the Korean Nurses’ Survey, conducted from October to December 2011, using web-based self-administered questionnaires. A total of 9,989 nurses were included among 10,000 who registered on the survey web site (5,287 shift workers and 4,702 non-shift workers). Current shift workers were divided into tertiles of shift work duration (0.08–3.00 years, n = 1,732; 3.08–6.75 years, n = 1,731; and 6.83–38.00 years, n = 1,686). The BMI thresholds of overweight and obesity were ≥23 kg/m2 and ≥25 kg/m2, respectively. Data were analyzed using SPSS software. Results: Mean participant age was 33.2 ± 8.6 years and the mean BMI was 20.9 ± 2.5 kg/m2. There were statistically significant differences in current smoking status, regular drinking habit, dietary habits, regular exercise, sleep problems and self-perceived health status according to duration of shift work. The overall prevalence of overweight/obesity (18.6%) and obesity (7.4%) increased significantly as shift work duration increased from the lowest to highest tertile (P for trend <0.001). Multivariate logistic regression analysis revealed no association between current shift work and BMI. However, after adjusting for potential confounders, the participants with the longest duration of shift work were 1.63 (95% CI, 1.22–2.17) times more likely to be overweight or obese than those with the shortest duration. There was a significant positive association between obesity and shift work duration in the unadjusted analysis; however, it was attenuated and no longer significant in the multivariate model. Conclusions: The duration of shift work was positively associated with prevalence of overweight/obesity in nurses in Korea. Although these findings need to be confirmed in prospective studies, they suggest that special attention should be paid to female nurses with a long duration of shift work

Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models

<p>Abstract</p> <p>Background</p> <p>In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.</p> <p>Results</p> <p>Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.</p> <p>Conclusion</p> <p>Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.</p

Isolation and Characterization of a Defensin-Like Peptide (Coprisin) from the Dung Beetle, Copris tripartitus

The antibacterial activity of immune-related peptides, identified by a differential gene expression analysis, was investigated to suggest novel antibacterial peptides. A cDNA encoding a defensin-like peptide, Coprisin, was isolated from bacteria-immunized dung beetle, Copris tripartitus, by using differential dot blot hybridization. Northern blot analysis showed that Coprisin mRNA was up-regulated from 4 hours after bacteria injection and its expression level was reached a peak at 16 hours. The deduced amino acid sequence of Coprisin was composed of 80 amino acids with a predicted molecular weight of 8.6 kDa and a pI of 8.7. The amino acid sequence of mature Coprisin was found to be 79.1% and 67.4% identical to those of defensin-like peptides of Anomala cuprea and Allomyrina dichotoma, respectively. We also investigated active sequences of Coprisin by using amino acid modification. The result showed that the 9-mer peptide, LLCIALRKK-NH2, exhibited potent antibacterial activities against Escherichia coli and Staphylococcus aureus

Ubiquitous-Severance Hospital Project: Implementation and Results

OBJECTIVES: The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements. METHODS: Clinical Data Repository (CDR) of u-Severance involved implementing electronic medical records (EMR) as the basis of EHR and the management of individual health records. EHR were implemented with service enhancements extending to the clinical decision support system (CDSS) and expanding the knowledge base for research with a repository for clinical data and medical care information. RESULTS: The EMR system of Yonsei University Health Systems (YUHS) consists of HP integrity superdome servers using MS SQL as a database management system and MS Windows as its operating system. CONCLUSIONS: YUHS is a high-performing medical institution with regards to efficient management and customer satisfaction; however, after 5 years of implementation of u-Severance system, several limitations with regards to expandability and security have been identifiedope

Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019)

Background The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults. Methods This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability. Results The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (p<0.001, p=0.041, and p<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69–3.10; p=0.027–0.038), especially in daughters (OR, 2.04–4.64; p=0.029–0.034). Conclusion HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli