• Biomolecules & Therapeutics
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• 제17권2호
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• pp.205-210
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• 2009

The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.84-88
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• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

• Journal of Korean Neurosurgical Society
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• 제53권6호
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• pp.349-355
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• 2013

Objective : Recently, microscope-integrated near infrared indocyanine green videoangiography (ICG-VA) has been widely used in cerebrovascular surgery because it provides real-time high resolution images. In our study, we evaluate the efficacy of intraoperative ICG-VA during cerebrovascular surgery. Methods : Between August 2011 and April 2012, 188 patients with cerebrovascular disease were surgically treated in our institution. We used ICG-VA in that operations with half of recommended dose (0.2 to 0.3 mg/kg). Postoperative digital subtraction angiography and computed tomography angiography was used to confirm anatomical results. Results : Intraoperative ICG-VA demonstrated fully occluded aneurysm sack, no neck remnant, and without vessel compromise in 119 cases (93.7%) of 127 aneurysms. Eight clipping (6.3%) of 127 operations were identified as an incomplete aneurysm occlusion or compromising vessel after ICG-VA. In 41 (97.6%) of 42 patients after carotid endarterectomy, the results were the same as that of postoperative angiography with good patency. One case (5.9%) of 17 bypass surgeries was identified as a nonfunctioning anastomosis after ICG-VA, which could be revised successfully. In the two patients of arteriovenous malformation, ICG-VA was useful for find the superficial nature of the feeding arteries and draining veins. Conclusion : ICG-VA is simple and provides real-time information of the patency of vessels including very small perforators within the field of the microscope and has a lower rate of adverse reactions. However, ICG-VA is not a perfect method, and so a combination of monitoring tools assures the quality of cerebrovascular surgery.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.165-172
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• 1999

In the present work , the transport mechanism of a capsaicin derivative, DA-5018, through blood-brain barrier (BBB) has been investigated to evaluate the feasibility of potential drug development. The result of pharmacokinetic parameters obtained from the intravenous injection of plasma volume marker,$[3^H]RSA$ and $[{14}^C]DA-5018$, indicated that both AUC, area under the plasma concentration curve and VD, volume of distribution in brain of $[3^H]RSA$ agreed with those reported ($1620{\pm}10 $percentage injected dose minute per milliliter (%IDmin/ml) and $12.0{\pm}0.1{\mu}l/g$, respectively). Elimination half-life and AUC of $[{14}^C]DA-5018$is corrected by the PHLC analysis, 19.6$\pm$1.2 min and 7.69$\pm$0.85% IDmin/ml, respectively. The metabolic rate of $[{14}^C]DA-5018$was very rapid. The blood-brain barrier permeability surface area (PS) product of $[{14}^C]DA-5018$ was calculated to be 0.24$\pm$0.05 $\mu$l/min/g. The result of internal carotid artery perfusion and capillary depletion suggested that [14C]DA-5018 pass through BBB with the time increasingly. Investigation of transport mechanism of $[{14}^C]DA-5018$ using agonist and antagonist suggested that vanilloid (capsaicin) receptor did not exist in the BBB, and nutrient carrier system in the BBB has no effect on the transport of DA-5018. In conclusion, despite the fact that penetration of DA-5018 through BBB is significant, the intact drug found in the brain tissue is small because of a rapid metabolism. Therefore, for the central analgesic effect of DA-5018, the method to increase the metabolic stability in plasma and the brain permeability should be considered.

• 한국환경보건학회지
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• 제44권6호
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• pp.524-538
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• 2018

Objective: This study aimed to identify the size distributions of particulate matter emitted during 3D printing according to operational conditions and estimate particle inhalation exposure doses at each respiratory region. Methods: Four types of printing filaments were selected: acrylonitrile-butadiene-styrene (ABS), polylactic acid (PLA), Laywood, and nylon. A fused deposition modeling (FDM) 3D printer was used for printing. Airborne particles between 10 nm and $10{\mu}m$ were measured before, during, and after printing using real-time monitors under extruder temperatures from 215 to $290^{\circ}C$. Inhalation exposures, including inhaled and deposited doses at the respiratory regions, were estimated using a mathematical model. Results: Nanoparticles dominated among the particles emitted during printing, and more particles were emitted with higher temperatures for all materials. Under all temperature conditions, the Laywood emitted the highest particle concentration, followed by ABS, PLA, and nylon. The particle concentration peaked for the initial 10 to 20 minutes after starting operations and gradually decreased with elapsed time. Nanoparticles accounted for a large proportion of the total inhaled particles in terms of number, and about a half of the inhaled nanoparticles were estimated to be deposited in the alveolar region. In the case of the mass of inhaled and deposited dose, particles between 0.1 and $1.0{\mu}m$ made up a large proportion. Conclusion: The number of consumers using 3D printers is expected to expand, but hazardous emissions such as thermal byproducts from 3D printing are still unclear. Further studies should be conducted and appropriate control strategies considered in order to minimize human exposure.

• 한국물환경학회지
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• 제37권6호
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• pp.501-509
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• 2021

In 2018, total 263 micro and emerging contaminants were selected as target substances by the Ministry of Environment, and 80 of them were first-class substance including endocrine disruptors, residual Pharmaceuticals and Personal Care Products (PPCPs), residual organic pollutants, pesticides and heavy metals. In this study, in order to evaluate the Hazard Quotient (HQ) of the 80 types in the domestic water environment the concentration of discharged effluent and nearby water environment reported by Korean institutes since 2010 was investigated. There were 45 substances reported to be detected, and Measurement Environment Concentration (MEC) were obtained by collectively converting them into water environment concentration. For biotoxicity, half maximal Effective Dose (EC50) to Daphnia magna, a water fleas species widely adopted in Material Safety Data Sheet (MSDS) was applied. As for the biotoxicity level, the Predicted No-Effect Concentration (PNEC) was obtained by applying the Assessment Factor (AF) and the HQ was derived by dividing it from the MEC. As a result of calculating the HQ, more than 1 substances were Cabamazepine, Mefenamic acid, Acetaminophen, Ibuprofen, Nonylphenol, Nickel, Erythromycin, Acetylslic acid, etc. Meanwhile, perfluorinated compounds were identified as hazardous substances in the water env ironment, with 5 out of 14 species included in the 20 ranks of first-class substance.

• Journal of Audiology & Otology
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• 제25권1호
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• pp.27-35
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• 2021

Background and Objectives: This study aimed to evaluate the clinical features and the clinical factors associated with prognosis of sudden sensorineural hearing loss (SSNHL) in diabetic patients. Subjects and Methods: Forty-nine diabetic with unilateral SSNHL were retrospectively included. All patients received systemic high dose steroid therapy within one month after onset and had more than one month of follow-up audiogram. The basic characteristics of the patients, initial and follow-up audiograms, laboratory data, and methods of steroid treatment were collected. Results: Compared to reference values in healthy subjects, 79%, 55%, and 45% of the patients had higher values of mean neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), respectively. Older patients had significantly less degree of hearing loss, but they also had significantly worse hearing thresholds in the unaffected ear. After steroid treatment, less than half patients (47%) showed hearing recovery. Simultaneous intratympanic dexamethasone (ITD) injections with systemic steroid did not confer an additional hearing gain or an earlier recovery rate in diabetic patients with SSNHL. In the multivariate analysis, initial hearing thresholds of affected ear and timing of steroid treatment were significantly associated with hearing prognosis in diabetic patients with SSNHL. Conclusions: Diabetic patients with SSNHL tended to have increased NLR, LMR, and PLR, which are reported to be associated with microvascular angiopathy. Simultaneous ITD injections to improve hearing recovery in diabetic patients with SSNHL seems unnecessary.

• 대한청각학회지
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• 제25권1호
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• pp.27-35
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• 2021

Background and Objectives: This study aimed to evaluate the clinical features and the clinical factors associated with prognosis of sudden sensorineural hearing loss (SSNHL) in diabetic patients. Subjects and Methods: Forty-nine diabetic with unilateral SSNHL were retrospectively included. All patients received systemic high dose steroid therapy within one month after onset and had more than one month of follow-up audiogram. The basic characteristics of the patients, initial and follow-up audiograms, laboratory data, and methods of steroid treatment were collected. Results: Compared to reference values in healthy subjects, 79%, 55%, and 45% of the patients had higher values of mean neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), respectively. Older patients had significantly less degree of hearing loss, but they also had significantly worse hearing thresholds in the unaffected ear. After steroid treatment, less than half patients (47%) showed hearing recovery. Simultaneous intratympanic dexamethasone (ITD) injections with systemic steroid did not confer an additional hearing gain or an earlier recovery rate in diabetic patients with SSNHL. In the multivariate analysis, initial hearing thresholds of affected ear and timing of steroid treatment were significantly associated with hearing prognosis in diabetic patients with SSNHL. Conclusions: Diabetic patients with SSNHL tended to have increased NLR, LMR, and PLR, which are reported to be associated with microvascular angiopathy. Simultaneous ITD injections to improve hearing recovery in diabetic patients with SSNHL seems unnecessary.

• Archives of Plastic Surgery
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• 제48권4호
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• pp.361-365
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• 2021

Background Pain in the postoperative body contouring patient has traditionally been managed with narcotic medication. In an effort to minimize side effects and prevent addiction, plastic surgeons are searching for novel ways to provide adequate analgesia, one of which is nerve blocks. This study was conducted with a meta-analysis that evaluates the efficacy of these blocks for patients who undergo breast surgery. Methods A search of the PubMed/MEDLINE database for articles including the terms "post-operative analgesia" OR "postoperative pain management" AND "in plastic surgery" OR "in cosmetic surgery" OR "in elective surgery" in February 2019 generated five studies on elective breast augmentation and reduction mammoplasty that reported pain scores and quantities of opioids consumed. Independent samples t-tests, one-way analysis of variance, and a random effects model were implemented for evaluation. Results A total of 317 patients were identified as having undergone body contouring of the breast, about half of which received a nerve block. Pain scores on a 1-10 scale and opioid dose-equivalents were calculated. Those who were blocked had an average score of 2.40 compared to 3.64 for those who did not (P<0.001), and required an average of 5.20 less narcotic doses (P<0.001). Pain relief following subpectoral augmentation was best achieved with type-II blocks as opposed to type-I and type-II with serratus plane (P<0.001). Conclusions The opioid epidemic has extended to all surgical specialties. Implementation of a nerve block seems to be an efficacious and cost-effective mechanism to not only help with post-operative pain, but also lower the need for narcotics, especially in subpectoral augmentation.

• Journal of Veterinary Science
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• 제23권5호
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• pp.64.1-64.9
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• 2022

Background: Fluralaner is a novel drug belonging to the isoxazoline class that acts on external parasites of domestic animals. It is used systemically via drinking water, especially against red poultry mite in layer chickens. Fluralaner is frequently used in layers infected with D. gallinae. However, no study to date has investigated the effects of feed intake and water hardness. Objectives: This study aimed to investigate the effects of variable water hardness and feed intake on the pharmacokinetic profile of fluralaner. Methods: Layer chickens were divided into four groups (n = 8): fed + purified water (Group 1), feed restricted + purified water (Group 2), feed restricted + hard water (Group 3), and feed restricted + soft water (Group 4). After administering a single dose of the drug with drinking water, the blood samples were collected for 21 days. Fluralaner concentrations in plasma samples were determined by liquid chromatography/tandem mass spectrometry. The maximum plasma concentration (C_max), time to reach maximum plasma concentration (t_max), area under the concentration-time curve values (AUC_0-21d), half-life (t_1/2), and other pharmacokinetic parameters were calculated. Results: Although the highest maximum plasma concentration (C_max) was determined in Group 1 (fed + purified water), no statistically significant difference was found in the C_max, t_max, t_1/2, MRT_{0-inf_obs}, Vz/F_obs, and Cl/F_{_obs} parameters between the experimental groups. Conclusions: It was concluded that the feed intake or water hardness did not change the pharmacokinetic profile of fluralaner in layer chickens. Therefore, fluralaner could be used before or after feeding with the varying water hardness in poultry industry.