• Journal of Microbiology and Biotechnology
• /
• 제32권6호
• /
• pp.816-823
• /
• 2022

The rapid spread of superbugs leads to the escalation of infectious diseases, which threatens public health. Endolysins derived from bacteriophages are spotlighted as promising alternative antibiotics against multi-drug resistant bacteria. In this study, we isolated and characterized the novel Salmonella typhimurium phage PBST08. Bioinformatics analysis of the PBST08 genome revealed putative endolysin ST01 with a lysozyme-like domain. Since the lytic activity of the purified ST01 was minor, probably owing to the outer membrane, which blocks accessibility to peptidoglycan, antimicrobial peptide cecropin A (CecA) was fused to the N-terminus of ST01 to disrupt the outer membrane. The resulting CecA::ST01 has been shown to have increased bactericidal activity against gram-negative pathogens including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Enterobacter cloacae and the most affected target was A. baumannii. In the presence of 0.25 µM CecA::ST01, A. baumannii ATCC 17978 strain was completely killed and CCARM 12026 strain was wiped out by 0.5 µM CecA::ST01, which is a clinical isolate of A. baumannii and resistant to multiple drugs including carbapenem. Moreover, the larvae of Galleria mellonella could be rescued up to 58% or 49% by the administration of CecA::ST01 upon infection by A. baumannii 17978 or CCARM 12026 strain. Finally, the antibacterial activity of CecA::ST01 was verified using 31 strains of five gram-negative pathogens by evaluation of minimal inhibitory concentration. Thus, the results indicate that a fusion of antimicrobial peptide to endolysin can enhance antibacterial activity and the spectrum of endolysin where multi-drug resistant gram-negative pathogens can be efficiently controlled.

• Archives of Pharmacal Research
• /
• 제9권2호
• /
• pp.81-86
• /
• 1986

The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.

• 생약학회지
• /
• 제30권1호
• /
• pp.40-47
• /
• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural hesperetin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Hesperetin inhibited plaque formations of HSV-1 and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-2 with selectivity index (SI) of 9.8 than on HSV-1 with SI of 8.4. The combined antiherpetic effects of hesperetin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of hesperetin with acyclovir on HSV-1 and HSV-2 showed synergistic effects with CI values of $0.29{\sim}0.73$ for 50%, 70%, 90% effective levels and those with vidarabine showed partially synergistic or additive effects with CI values of $0.83{\sim}1.33$.

• 대한간호학회지
• /
• 제15권2호
• /
• pp.5-15
• /
• 1985

This study was conducted for the purpose of fin-ding out the variance explaining the medical facilities utilization behavior, which is defined adaptation behavior Process by focal, contextual, residual stimuli in Roy's Adaptation Model. What kinds of characteristics can explain adaptation behavior in Roy's Model? And which is the relative importance of input variables? For this analysis, stepwise multiple regression and path analysis was used. The data come from the 1981 Baseline Household Interview Survey in remote rural area. The findings of the analysis can be summarized as follows: First, Total variance of independant variables for adaptation behavior, that is medical facilities utilization including clinic, drug store, health center, herb medicine was shown 16.2 percent. The most important variable which explain the dependent variable was the occurance of illness with the Ra of value 0.112. The illness symptom, living level, regular care source was shown important variables with relatively high the R²value and significant beta coefficient. Second, in the path analysis of variables which is selected important variables, the occurance of illness was shown variable which has the highest direct effect which 0.297 path coefficient. Also the education level of household was shown variable which has the highest indirect effect through living level and the occurance of illness in causal model. Third, This analysis suggests that the occurance of illness belonging focal stimuli are more influenced than others. To sum up, It is seem to the occurance of illness, illness symptom belonging focal stimuli have high explanation ability through direct effect, education level of household among contextual stimuli have explanation ability through indirect effect.

• 약학회지
• /
• 제20권1호
• /
• pp.63-69
• /
• 1976

Prednisolone tablet product design problem was structured as constrained optimization problem and subsequently solved by multiple regression analysis and Lagrangian method of optimixation. Prednisolone was the drug chosen and anhydrous lactose and corn starch were the adjuvants. The effect of anhydrous lactose and corn starch concentrations on tablet hardness, volume, disintegration time and in vitro release rate was studied. The concentrations of anhydrous lactose and corn starch used in this experiment were 30-60 percent and 5-30 percent, respectively. A full second-order (quadratic) model with all possible two-factor interactions was employed. To obtain the values of anhydrous lactose and corn starch which miniumize the in vitro : release time (t$_{60%}$) subject to the constraint on tablet hardness, disintegration time and volume, we solved the Lagrange function. Multiple correlation coefficients for the regression models were correlated at less than 0.05 level and it was found that the optimum concentrations of anhydrous lactose and corn starch were 45 percent and 21 percent, respectively.

• Laboraroty Animal Research
• /
• 제34권4호
• /
• pp.248-256
• /
• 2018

O-2-$^{18}F$-fluoroethyl-l-tyrosine ($[^{18}F]FET$) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of $[^{18}F]FET$ for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only $[^{18}F]FET$ uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that $[^{18}F]FET$ PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, $[^{18}F]FET$ uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson's correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that $[^{18}F]FET$ PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

• 한국병원경영학회지
• /
• 제24권2호
• /
• pp.12-22
• /
• 2019

Purposes: The purpose of this study was to examine the association between risk behaviors and smoking in Korean adolescents. Methods: This study used data from online survey of youth health behavior in 2017. Data from a total of 54,411 people (27,139 male, 27,272 female) were included in the analysis. chi-square test, simple logistic regression, multiple logistic regression were performed using SAS 9.4. Findings: Multiple logistic regression analysis showed that risk behaviors such as drinking alcohol experience, sexual experience, drug use experience and high caffeine energy drinks intake experience had a significant effect on smoking. Adolescents with drinking experience were more likely to smoking than those who had no experience(OR=8.58, 95% CI: 7.67~9.60). Adolescents with sexual experience were more likely to smoking than those who had no experience(OR=4.47, 95% CI: 3.91~5.11). Adolescents with drug use experience were more likely to smoking than those who had no experience(OR=2.32, 95% CI: 1.63~3.32). Also, adolescents with high-caffeine energy drinks intake experience were more likely to smoking than those who had no experience(OR=1.37, 95% CI: 1.23~1.53). Practical Implications: All the risk behaviors were significantly associated with smoking rates. Results of this study suggest that physicians and health workers in medical institutions and health centers should simultaneously serve education and consultation for the smoking cessation as well as for the prevention of risk behaviors.

• 한국수정란이식학회:학술대회논문집
• /
• 한국수정란이식학회 2002년도 국제심포지엄
• /
• pp.109-109
• /
• 2002

In recent reports, the multiple reproductive defects such as cryptorchidism, hypospadias, epididymal cysts, low sperm counts, and testicular cancers are increased in humans, and these changes were doubted by the chemicals with estrogenic or antiandrogenic activities in our environment. To compare the effects of neonatal exposure of di (n-butyl) phthalate and flutamide on the development of reproductive organs and to identify the specific mechanisms of these abnormalities related to the male reproducton, Sprague-Dawley neonate male rats were injected subcutaneously during 5-14 days after birth with corn oil (control), flutamide (0.05, 0.1, and 0.5 mg/animal) and DBP (5, 10, and 20 mg/animal). Animals were killed at 31 (immature) and 42 (pubertal) days of age respectively and blood was collected from abdominal aorta for serum testosterone analysis. Testes, epididymides, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscle (LABC), cowpers glands and glans penis were weighed. Expression of steroid hormone receptors (AR and ER) was examined in the testes and ventral prostate. At 31 days of age, ventral prostate, seminal vesicles, LABC, and cowpers glands significantly decreased in the flutamide (0.5 mg/animal) and DBP (20 mg/animal), but serum testosterone levels were not changed. Flutamide slightly delayed the testes descent at the high dose (0.5 mg/animal), but DBP did not show any significant effect on the testes descent at all doses. DBP and flutamide decreased the expression of AR protein in the testes but did not affect the expression of ERa and ER protein in the testes. At 42 days of age, ventral prostate, seminal vesicles, and cowpers glands weights were still significantly decreased at the high dose of flutamide (0.5 mg/animal) and DBP (20 mg/animal), but the weights of testes and epididymides were not different. Serum testosterone decreased significantly in DBP treated animals and slightly, not significantly, in flutamide group. While DBP still significantly decreased the expression of AR protein in testis, flutamide recovered from downregulation of AR protein and did not affect the expression of ERa and ER protein in the testes. Based on these results, flutamide and DBP have shown several similar patterns in reproductive abnormalitis, but some marked differences which may be caused by different acting mechanism.

• Journal of Pharmaceutical Investigation
• /
• 제35권4호
• /
• pp.287-293
• /
• 2005

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, Amaryl tablet (Handok & Aventis Korea, reference drug) and Mepiril tablet (Myungmoon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (glibenclamide) to human plasma, plasma samples were extracted using 1mL of methyl tertiary butyl ether. Compounds extracted were analyzed by reverse-phase HPLC with multiple reaction monitoring (MRM) mode analyte detection. This method for determination glimepiride proved accurate and reproducible, with a limit of quantitation of 2 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the glimepiride dose of 2 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of glimepiride were monitored by a LC-MS/MS for over a period of 12 hr after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Amaryl/Mepiril were log 0.9583-log 1.1357 and log 1.0570-log 1.2376, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Taken together, our study demonstrated the bioequivalence of Amaryl and Mepiril with respect to the rate and extent of absorption.

• 대한간호학회지
• /
• 제51권4호
• /
• pp.414-429
• /
• 2021

Purpose: This systematic review and meta-analysis analyzed the effects of 2% chlorhexidine bathing on the incidence of hospital-acquired infection (HAI) and multidrug-resistant organisms (MDRO) in adult intensive care units. Methods: PubMed, CINAHL, Cochrane library, and RISS database were systematically searched, and 12 randomized studies were included in the analysis. Comprehensive Meta-Analysis version 3.0 was used to calculate the effect size using the odds ratio (OR) and a 95% confidence interval (CI). Subgroup analysis was performed according to the specific infection and intervention types. Results: In general, 2% chlorhexidine bathing has a significant effect on the incidence of HAI (OR, 0.59; 95% CI, 0.40~0.86) and MDRO (OR, 0.52; 95% CI, 0.34~0.79). Subgroup analyses show 2% chlorhexidine bathing is effective in bloodstream infections (OR, 0.51; 95% CI, 0.39~0.66) but not for urinary tract infections, ventilator-associated pneumonia infections, and Clostridium difficile infections. Moreover, 2% chlorhexidine bathing alone or its combination with other interventions has a significant effect on the incidence of HAI and MDRO (OR, 0.59; 95% CI, 0.38~0.92). Conclusion: This meta-analysis reveals that 2% chlorhexidine bathing significantly reduces the incidence of HAI and MDRO in intensive care units. The effect of 2% chlorhexidine bathing on pediatric patients or patients at general wards should be further assessed as a cost-effective intervention for infection control.