• Title/Summary/Keyword: Drug Distribution

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Complexation of Amphotericin B With Egg Phosphatidylcholine Liposomes

  • Kim, Jin-Chul;Lee, Eun-Ok;Yang, Ji-Won;Choe, Tae-Boo;Kim, Jong-Duk
    • Archives of Pharmacal Research
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    • v.18 no.2
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    • pp.84-89
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    • 1995
  • The complexation and physical characteristics of egg phosphatidylcholine (PC) liposome containing amphotericin B(AmB) were investigated through circular dichrosim(CD) spectra, the size distribution, the turbidity change, and the calcein release. CD spectra of AmB-containing egg PC mxture exhibited a positive peak around 330 nm indicative of complexation of AmB and four negative peaks. The positive peak increased up to $2.2{\;}millidegree/{\mu}g$ AmB as AmB contents increased up to 12% (w/w), suggesting that AmB-phospholipid complexation was promoted by the antibiotics. The effective diameter of liposomesa by dynamic light scattering decreased from 450 nm to 220 nm as the amount of AmB in liposomes increased from o to 30% (w/w). The complexation may be responsible for the reduction in size. On the other hand, at around 1 mN deoxycholate (DOC), the reltive turbidities of 5 and 10% (w/w) AmB-containing liposome suspension were less than 1 probably due to the soblubilization of the complex, while those of pure PC liposome suspension were larger than 1 at the same concentration. Deoxycholate-induced release of liposomes, indicating the intercalation of the drug into the bilayers. Therefore, it is concluded that in AmB/eggPC/water system, AmB-phospholipid complexcoexists with AmB-containing liposomes.

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Bioavailability of Microspheres Containing Felodipine (필로디핀이 함유된 미립구의 생체이용률)

  • 양재헌;나성범;김영일;김남순
    • YAKHAK HOEJI
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    • v.44 no.5
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    • pp.440-447
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    • 2000
  • Microspheres of felodipine, which is one of the calcium channel blocker using a mixture of Eudragi $t^{R}$ RL, L, E, and cellulose on the base of Eudragi $t^{R}$ RS were investigated. Cremopho $r^{R}$ was added to each preparation of polymers in order to increase the release of felodipine from microspheres. Felodipine-loaded microspheres were prepared by a solvent evaporation method, which is based on dispersion of methylene chloride containing felodipine and polymers in 0.5 w/v % polyvinyl alcohol solution. The average diameter based on the size distribution of the felodipine-loaded microspheres was observed to be ca. 40-55 ${\mu}{\textrm}{m}$. A good and smooth surface were showed in all types of the microspheres. The amount of felodipine loaded was over 90 w/w % in all types of microspheres. The dissolution profiles of felodipine from microspheres were similar with each type of polymer, and about a 60 w/w % of the total amount of felodipine loaded to microsphere was released within 7 hours. Dissolution rate of felodipine from the microsphere was increased by addition of Cremophor. After oral administration of the felodipine-loaded microspheres in PVA solution and felodipine alone in PEG solution to rats, respectively, the pharmacokinetic study revealed that the Tmax values of the microspheres were observed in the range of 0.67~l.0 hr while that of the felodipine solution was obtained 0.33 hr. In addition, the AUC of the microspheres at 0 to 7 hr was remarkably increased in comparison to that of felodipine solution. These results revealed that the microspheres based on Eudragit RS could be a good candidate for the controlled release drug delivery system for felodipine.e.e.e.

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The Convergence Effect of Histamine and Atropine on Intestinal Contractility (위장관 수축성에 대한 Histamine과 Atropine의 융합성 조절 효과)

  • Je, Hyun Dong;Min, Young Sil
    • Journal of Convergence for Information Technology
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    • v.11 no.10
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    • pp.131-137
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    • 2021
  • The aim of the study was to observe the influence and related mechanism of histamine and its analogues used for hypersensitivity tests and used as an indicator of impurities in drugs on the tissue-specific intestinal contraction. Intestinal contraction includes the activation of thick or thin filament regulation. However, there are few reports addressing the question whether this regulation is involved in histamine-induced regulation. We hypothesized that histamine plays a role in tissue-dependent regulation of intestinal contractility. Denuded ileal/colonic longitudinal and circular muscles of male rats were used and isometric contractions were recorded using a data acquisition system. Interestingly, histamine alone didn't increase the contraction of the circular muscle but increased the contraction of the longitudinal muscle. Histamine together with atropine (M3 receptor antagonist) didn't inhibit the contraction of the longitudinal and circular muscle. Therefore, histamine alone and together with atropine increases the ileal longitudinal muscle contraction suggesting that additional mechanisms (decreased receptor density, postreceptor signaling or distribution of agonists) might be involved in the regulation of ileal muscle contractility. In conclusion, histamine and/or atropine has some effect on the regulation of the longitudinal contractility regardless of M3 receptor and the simpler test would be preferred as the drug impurity test compared to more complicated tests.

ABT-737 ameliorates docetaxel resistance in triple negative breast cancer cell line

  • Hwang, Eunjoo;Hwang, Seong-Hye;Kim, Jongjin;Park, Jin Hyun;Oh, Sohee;Kim, Young A;Hwang, Ki-Tae
    • Annals of Surgical Treatment and Research
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    • v.95 no.5
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    • pp.240-248
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    • 2018
  • Purpose: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2). Methods: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases. Results: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment. Conclusion: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.

Antimicrobial and Cell Viability Measurement of Hypochlorous Acid against Streptococcus. mutans and Aggregatibacter. actinomycetemcomitans (미산성 차아염소산수의 S. mutans와 A. actinomycetemcomitans에 대한 살균 효과)

  • Song, Jiyeon;Kim, Jiyoung;Lee, Kyunghee
    • Journal of The Korean Society of Integrative Medicine
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    • v.7 no.2
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    • pp.141-151
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    • 2019
  • Purpose : Hypochlorous acid (HOCl), a major inorganic bactericidal compound of innate immunity, is effective against a broad range of microorganisms. In particular, HOCl is well-known as a non-antibiotic antimicrobial substance. However, effects of HOCl as an antimicrobial agent are still needed to study these functions against various specific type of microorganisms. In this study, we investigated the antimicrobial effect of hypochlorous acid (HOCl) in S. mutans and A. actinomycetemcomitans to cause dental caries and periodontal disease. Experiments were conducted to observe whether HOCl become effective replacement of disinfectant. Methods : To observe antimicrobial effect of HOCl, stabilized HOCl is prepared in the form of a physiologically balanced solution in pre-conditioned and post-conditioned HOCl solution. As a control, commercially available disinfectant MAXCLEAN was used as positive control. Moreover, S. mutans and A. actinomycetemcomitans distribution in gagrin, filtered tap water, and culture media. Cell viability were measured by viable cell count methods and disk diffusion test. Results : Our results showed that treatment of HOCl have no effect against antimicrobial effect compare to control group especially gagrin in disk diffusion test. HOCl tended to reduced viability against S. mutans in group of post-conditioned than pre-conditioned of HOCl solution however, there was no significant difference as well as no effect in A. actinomycetemcomitans. Conclusion : HOCl showed tendency to reduce viability against S. mutans in group of post-conditioned of HOCl solution and no effect of antimicrobial effect. Although HOCl is well known as effective against a broad range of microorganisms, HOCl seems to have diversity following type of species to be used as antimicrobial drug following our results. Therefore, it is necessary to be rigidly controlled and regulated in using HOCl solution clinically.

Bacteriological and Chemical Hazard Analysis in Commercial Fish Products Minimally Processed (시판 어류 단순가공품의 세균학적 및 화학적 위해요소 분석)

  • Kim, Hyun-Jung;Lee, Dong-Soo;Kim, Il-Hoe;Kim, Young-Mog;Shin, Il-Shik
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.52 no.1
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    • pp.19-26
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    • 2019
  • The objective of this study was to analyze bacteriological and chemical hazards in minimally processed commercial fish products, including Hwangtae (freeze-dried pollock), dried anchovy, fermented anchovy sauce, and salted and dried yellow croaker. Escherichia coli counts from all samples were below the regulation limits of the Korean Ministry of Food and Drug Safety Standards on Quality of Seafood and Seafood Products (Food Code). However, the food poisoning bacterium Staphylococcus aureus was detected at levels above $1.0{\times}10^2$ colony forming units (CFU)/g in Hwangtae, dried anchovy, and salted and dried yellow croaker, which are commonly ingested without heating and pose bacteriological hazards. The detection of S. aureus, an organism indicative of poor personal hygiene, which can be introduced by employees and multiply during distribution, indicates the necessity of improving the sanitary control of minimally processed commercial fish products. Histamine was not detected from dried anchovy or salted and dried yellow croaker, but was detected at some of the highest levels in fermented anchovy sauces. This result suggests that efforts to reduce the amount of histamine in fermented anchovy sauces are required.

A Study on Identification Keys of Araliae Continentalis Radix and its Adulterants : Focused on External·Internal Morphology and Pattern Analysis (독활(獨活)과 그 위품의 감별기준 연구 : 외·내부형태 및 이화학패턴을 중심으로)

  • Yoon, Jee-Hyun;Ju, Young-Sung
    • The Korea Journal of Herbology
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    • v.33 no.2
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    • pp.29-43
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    • 2018
  • Objectives : Araliae Continentalis Radix(AC) is a medicinal herb belonging to the drug efficacy group treating musculoskeletal disorders(MSD) with anti-inflammatory, analgesic and antipyretic action. However, due to morphologic and onomastic similarity, adulterants(Angelicae Pubescentis Radix: AP, Gypsophilae Oldhamianae Radix: GO, Levistici Officinalis Radix: LO) have been included or replaced the standard. Methods : Multilateral methods were carried out on the identification of AC and its adulterants. Macroscopic and microscopic characteristics were observed by using stereoscope and microscope. For the comparison of chromatogram pattern, standard compounds were analyzed simultaneously using high performance liquid chromatography. Results : 1. The macroscopic identification of original plants was determined by the phyllotaxis type, the inflorescence type, the leaf margin and the color of flowers. The macroscopic identification of herbal materials was examined by oil spots, the cambium, heteromorphic vascular bundles, and the pholem. 2. For the microscopic identification, the fact whether its xylem ray is proliferated or not was first determined. Then medicinal herbs were secondly divided by cellular inclusions, fiber bundles, the distribution of secretary canals and the shape of cambium. 3. AC and its adulterants showed different chromatographic fingerprints. AC was containing continentalic acid and kaurenoic acid. AP was containing osthole and columbianadin. LO was containing osthole and falcarindiol. None of the compounds were found in GO. Conclusions : This recent identification keys of might be helpful to discriminate the pharmacopoeia standard and its adulterants for the right usage in clinics.

A Study on the Characteristics and Treatment Effects of Underweight Children and Adolescents Treated by Korean Medicine (한의 치료를 받은 저체중 소아청소년의 특성 및 치료 효과에 대한 고찰)

  • Kim, Hye Yeon;Kim, Ye Ji;Kim, Sang Min;Lee, Sun Haeng;Lee, Jin Yong
    • The Journal of Pediatrics of Korean Medicine
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    • v.36 no.3
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    • pp.49-62
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    • 2022
  • Objectives This study aimed to provide evidence for the use of Korean medicine in underweight patients by analyzing the medical records of underweight children and adolescents. Methods Children and adolescents who visited Korean pediatrics at Kyung Hee University Hospital from June 1, 2019 to May 31, 2022, who had an age-specific weight percentile which was less than 5 and diagnosed with E639.005 or R628.001 were selected for the study. A retrospective chart review was conducted by examining the medical records of subjects who received Korean medical treatment. The treatment effect was analyzed in all subjects and subgroups by comparing changes in height, weight, and body mass index (BMI) percentiles before and after Korean medicine treatment. Results A total of 55 underweight subjects were included in the study. General characteristics such as distribution by sex, age, number of visits, and weight percentile, and clinical characteristics such as diagnosis, past history, family history, drug history, current or past symptoms, and symptom differentiation were collected. The composition of herbal medicines and the contents of other Korean medical treatments were analyzed. In the case of treatment effect, the weight and BMI percentile of all subjects increased significantly. Conclusions This study was conducted to suggest Korean medicine as a method of proper weight management in children and adolescents. In the future, follow-up studies with a large number of subjects and controlled variables, such as the period of taking herbal medicine, are needed.

Hematocrit Determination using a Volumetric Absorptive Microsampling Technique in Patients with Pancreatic Cancer

  • Yeolmae Jung;Seunghyun Yoo;Minseo Kang;Hayun Lim;Myeong Hwan Lee;Ji Kon Ryu;Jangik Lee
    • Korean Journal of Clinical Pharmacy
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    • v.33 no.3
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    • pp.195-201
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    • 2023
  • Background: Hematocrit is usually measured from venous blood collected by invasive venipuncture. This study was performed to determine hematocrit accurately and precisely using minimally invasive volumetric absorptive microsampling (VAMS) technique. Such technique is to be applied to determining hematocrit in various clinical settings for the care, including therapeutic drug monitoring, of neonatal or epileptic patients, or patients with high risk of infection or bleeding. Methods: The study was performed using 31 VAMS samples obtained from 21 pancreatic cancer patients. Hematocrit was determined using the values of potassium concentrations obtained from blood in VAMS tips (HctVAMS). HctVAMS was compared with hematocrit measured from blood collected by venipuncture (HctVP). The accuracy and precision of HctVAMS in comparison to HctVP were evaluated using Bland-Altman plot, Deming regression and mountain plot. Results: Bland-Altman plot displayed a random scattering pattern of the differences between HctVAMS and HctVP with the mean bias of -0.010 and the 95% limit of agreement ranging from -0.063 to 0.044. Deming regression for HctVAMS and HctVP line demonstrated very small proportional and constant biases of 1.04 and -0.003, respectively. Mountain plot exhibited a narrow and symmetrical distribution of the differences with their median of -0.011 and central 95% range from -0.049 to 0.033. Conclusion: Hematocrit was accurately and precisely determined using less invasive VAMS technique. Such technique appears to be applicable to determining hematocrit in situations that venipuncture is not favorable or possible.

Isolation and Antimicrobial Susceptibility of Nontuberculous Mycobacteria in a Tertiary Hospital in Korea, 2016 to 2020

  • Keun Ju Kim;Seung-Hwan Oh;Doosoo Jeon;Chulhun L. Chang
    • Tuberculosis and Respiratory Diseases
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    • v.86 no.1
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    • pp.47-56
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    • 2023
  • Background: There is a global increase in isolation of nontuberculous mycobacteria (NTM). The aim of the study was to analyze longitudinal trends of NTM identification and pattern of antimicrobial susceptibility testing. Methods: NTM recovery rates, distribution of NTM species identification, and antimicrobial susceptibility pattern of NTM at Pusan National University Yangsan Hospital between January 2016 and December 2020 were retrospectively analyzed. Results: A total of 52,456 specimens from 21,264 patients were submitted for mycobacterial culture, of which 2,521 from 1,410 patients were NTM positive over five years (January 2016 to December 2020). NTM isolation showed an increasing trend from 2016 to 2020 (p<0.001, test for trend) mainly caused by Mycobacterium avium complex. The vast majority of M. avium complex were susceptible to key agents clarithromycin and amikacin. For Mycobacterium kansasii, resistance to rifampin and clarithromycin is rare. Amikacin was the most effective drug against Mycobacterium abscessus subspecies abscessus and Mycobacterium subspecies massiliense. Most of M. subspecies massiliense were susceptible to clarithromycin, while the majority of M. abscessus subspecies abscessus were resistant to clarithromycin (p<0.001). Conclusion: There was an increasing trend of NTM isolation in our hospital. Resistance to key drugs was uncommon for most NTM species except for M. abscessus subspecies abscessus against clarithromycin.