• Title/Summary/Keyword: therapeutic agents

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AcrAB-TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism

  • Soojin Jang
    • BMB Reports
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    • v.56 no.6
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    • pp.326-334
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    • 2023
  • Antibiotic resistance (AR) is a silent pandemic that kills millions worldwide. Although the development of new therapeutic agents against antibiotic resistance is in urgent demand, this has presented a great challenge, especially for Gram-negative bacteria that have inherent drug-resistance mediated by impermeable outer membranes and multidrug efflux pumps that actively extrude various drugs from the bacteria. For the last two decades, multidrug efflux pumps, including AcrAB-TolC, the most clinically important efflux pump in Gram-negative bacteria, have drawn great attention as strategic targets for re-sensitizing bacteria to the existing antibiotics. This article aims to provide a concise overview of the AcrAB-TolC operational mechanism, reviewing its architecture and substrate specificity, as well as the recent development of AcrAB-TolC inhibitors.

Skeletal Manifestations of Inborn Errors of Metabolism: A Comprehensive Retrospect (선천성 대사 이상 질환에서의 골격계 증상 발현)

  • Sung Yoon Cho
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.23 no.1
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    • pp.1-11
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    • 2023
  • Inborn errors of metabolism encompass a wide variety of disorders, frequently affecting bone. This review presents a comprehensive retrospect on the primary involvement of bone in inborn errors of metabolism. Primary involvement of bone in inborn errors of metabolism includes entities that primarily affect the bone marrow, mineral component or cartilage. These include lysosomal storage disorders, hypophosphatasia, and hereditary hypophosphatemic rickets. In this review, we discuss the primary involvement of bone in inborn errors of metabolism (hypophosphatasia, X-linked hypophosphatemic rickets, Gaucher disease, and mucopolysaccharidoses) along with the therapeutic agents used in clinical settings, diagnostic strategies, and general management. With the development of disease-specific targeted therapies and supportive care, more number of patients with these disorders live longer and survive into adulthood. Moreover, skeletal symptoms have become a more prominent feature of these disorders. This makes the awareness of these skeletal symptoms more important.

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The Therapeutic Efficacy and the Bleeding Complications of Urokinase and Alteplase in Patients with Massive Pulmonary Thromboembolism (중증 폐혈전색전증 환자에서 Urokinase와 Alteplase의 효과 및 출혈 합병증 비교)

  • Yoo, Jung-Wan;Kim, Wongyoung;Choi, Chang Min;Hong, Sang-Bum;Oh, Yeon Mok;Shim, Tae Sun;Lim, Chae-Man;Lee, Sang Do;Kim, Woo Sung;Kim, Dong Soon;Kim, Won Dong;Koh, Younsuck
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.1
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    • pp.6-12
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    • 2009
  • Background: The efficacy of several thrombolytic agents for treating massive pulmonary thromboembolism (PTE) has been reported to be similar. However, the difference of the bleeding complications caused by two commonly used thrombolytic agents in PTE patients is not well known. The aim of this study was to compare the therapeutic efficacy and the bleeding complications between urokinase and recombinant tissue-type plasminogen activatior (rt-PA, alteplase) in a Korean medical center. Methods: We retrospectively reviewed the clinical data of the patients who were treated with thrombolytic agents (urokinase and alteplase) because of massive PTE. Results: A total of 40 patients were included: 16 (40%) treated with urokinase and 24 (60%) with alteplase. The patients treated with alteplase showed a shorter duration of using vasopressor agents than did the patients who were given urokinase, but the duration of mechanical ventilation, the length of the ICU stay and the hospital stay were not different between the thrombolytic agents. Five patients treated with urokinase and eight patients treated with alteplase died (p=0.565): One patient in the urokinase group and four patients in the alteplase group died due to pulmonary thromboembolism. Bleeding complications after thrombolysis were observed in 3 patients (7.5%) treated with urokinase and in 11 (27.5%) patients treated with alteplase (p=0.079). Major bleeding complication occurred in 2 patients who were treated with alteplase. Conclusion: Urokinase seems to have fewer bleeding complications with an equivalent efficacy, as compared to alteplase, in Korean patients who suffer with massive pulmonary thromboembolism.

Effect of Dietary Chlorella Complex on Anticancer Activity in Mice

  • Jung Jae-Hak;Jin Kyong-Suk;Kim Yong-Ho;Lee Yong-Woo
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.185-192
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    • 2005
  • Dietary chlarella has known as one of the best candidates for development of multifunctional probiotic foods owing to an excellent nutritional value such as high amount of proteins and various, valuable fatty acids. So many efforts were devoted to studying the chlorella as therapeutic agents or foods fighting against many diseases in the aged people such as cardiovascular diseases and cancers. In this study, we investigated sizes and weights of tumors derived from mice injected subcutaneously with tumorigenic cells to see if antitumor activity would be found in mice dieted with the chlarella complex. After BALB/c mice were dieted with $5\%$ organic cultured chlorella complex diet throughout for 19weeks, the fibrosarcoma was induced by subcutaneous injection of tumorigenic cells at the 3 weeks before sacrifice. The average weight of tumors in the diet group were significantly reduced to $60\%\;(P=0.012)$ of the one in control group, indicating that diet with the chlarella complex may have anticancer activity in mice. When the mice were dieted with $5\%$ organic cultured chlorella complex for 4 weeks before injecting the tumorigenic cells in order to see tumor-preventive effect of the diet, the potential preventive activity of the diet against cancer was implicated by the observation that the tumors were greatly reduced in the diet group to $37\%$ (P=0.l44) of the control group. Especially, when the $5\%$ diet were applied to mice after injecting with the tumorigenic cells, the tumors derived from the $5\%$ diet group were also decreased to $95\%$ (P=0.002) of those in the control group, suggesting that the diet with the organic cultured chlorella complex may also have therapeutic effect against tumor formation. As results, it was shown that the chlorella complex tested in this study had preventive and therapeutic effects on fighting against tumorigenesis. Therefore, the identification and further mechanistic study of the components which may be associated with antitumor activity from diet of the chlorella complex in the future will contribute to the development of anticancer probiotic foods, alternative therapeutic treatment against cancer, and a new anticancer drug.

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Use of rapid diagnostic kit for the diagnosis of Korean native calf diarrhea (신속 진단 킷트를 활용한 한우 송아지의 설사증 원인체 검사)

  • Choe, Changyong;Jung, Young-Hun;Do, Yoon-Jung;Cho, Ara;Kim, Seong-Bum;Kang, Hee-Sung;Yoo, Jae-Gyu;Park, Jinho
    • Korean Journal of Veterinary Service
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    • v.40 no.1
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    • pp.61-66
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    • 2017
  • Calf diarrhea is a disease experienced by almost all of calves after birth and is one of the representative causes of damage to farmers due to mass mortality and of economic losses to them by inhibiting normal growth. In this study, we conducted quick detection of etiologic agents of diarrhea by using a rapid diagnostic kit to multiply diagnose antigens of five etiologic agents of calf diarrhea (rotavirus, coronavirus, Escherichia coli, Cryptosporidium, Giardia) in Hanwoo (Korean native cattle) calves. When the positive antigen proportion of the calf diarrheal feces for each farm was analyzed, rotavirus, coronavirus, Escherichia coli, Cryptosporidium, and Giardia showed antigen positive rates of 0~67%, 0~20%, 0~60%, 0~20%, and 0~67%, respectively. With regard to the antigen positive rate by age in days after birth, 1-week-old calves showed the antigen positive rate of 20% in rotavirus and 20% in Giardia, and 2-week-old calves showed that of 50% in rotavirus. In addition, 4-week-old calves showed the antigen positive rate of 10% in rotavirus, 10% in coronavirus, 10% in Escherichia coli, and 30% in Giardia, and 8-week-old calves showed the antigen positive rate of 17% in coronavirus, 50% in Escherichia coli, 17% in Cryptosporidium, and 33% in Giardia. Based on the results of this study, the etiologic agents of diarrhea in Hanwoo calves for each farm are widely distributed. Although younger than 2-week-old calves were strongly positive for rotavirus, older than 4-week-old calves were highly positive for Giardia and Escherichia coli. In conclusion, we considered that a rapid diagnostic kit is an effective method for quick detection of etiologic agents and would be helpful for cattle farmers and veterinarians to select appropriate therapeutic method.

A Monte Carlo Study of Dose Enhancement according to the Enhancement Agents (몬테칼로 기법을 이용한 방사선 선량증가 물질에 따른 선량증가 효과 평가)

  • Kim, Jung-Hoon;Kim, Chang-Soo;Hwang, Chulhwan
    • Journal of radiological science and technology
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    • v.40 no.1
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    • pp.93-99
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    • 2017
  • Dose enhancement effects at megavoltage (MV) X and ${\gamma}-ray$ energies, and the effects of different energy levels on incident energy, dose enhancement agents, and concentrations were analyzed using Monte Carlo simulations. Gold, gadolinium, Iodine, and iron oxide ($Fe_2O_3$) were compared as dose enhancement agents. For incident energy, 4, 6, 10 and 15 MV X-ray spectra produced by a linear accelerator and a Co-60 ${\gamma}-ray$ were used. The dose enhancement factor (DEF) was calculated using an ICRU Slab phantom for concentrations of 7, 18, and 30 mg/g. The DEF was higher at higher concentrations of dose enhancement agents and at lower incident energies. The calculated DEF ranged from 1.035 to 1.079, and dose enhancement effects were highest for iron oxide, followed by iodine, gadolinium, and gold. Thus, this study contributes to improving the therapeutic ratio by delivering larger doses of radiation to tumor volume, and provides data to support further in vivo and in vitro studies.

Comparison of MicroRNA Expression in Placenta-derived Mesenchymal Stem Cells and Bone Marrow-derived Stem Cells (태반유래 줄기세포와 골수유래 줄기세포에서의 마이크로RNA 발현비교)

  • Kim, Soo Hwan
    • Journal of Life Science
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    • v.24 no.11
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    • pp.1238-1243
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    • 2014
  • Mesenchymal stem cells (MSCs) have been widely used as cellular therapeutic agents. They have their own characteristic stemness, and thus, they can be used in the treatment of many chronic diseases and in anticancer therapy. MSC therapy has many advantages over chemical therapy. MSC therapy is based on self or homogeneous origin; as such, it is expected to be effective in the treatment of various diseases. In addition, microRNAs in particular have been studied for their structure and function, and they are also expected to prove effective for use as therapeutic agents in cancer or chronic diseases. MicroRNAs are largely associated with metabolism and homeostasis. Therefore, over- or under-expression of microRNAs leads to chronic diseases. Conversely, effective control of the expression of specific microRNAs reduces the risk of many chronic diseases. However, there have been no reports thus far on the synergistic effects of MSCs and microRNAs. Therefore, in this study, we examined the relationship between MSCs and microRNAs using placenta-derived MSCs (PDSCs), bone marrow-derived MSCs (BM-MSCs), and fibroblast (WI-38) cells. We studied the expression of some microRNAs in MSCs and compared the expression in each cell line and cell passage. As a result, we found that the expression of microRNA-34a was higher in PDSCs than in BM-MSCs and that the expression of microRNA-27a, 33a, 33b, and 211 was higher in BM-MSCs than in PDSCs. Therefore, we expect that each MSC line will be used as cell therapy, considering its expressed functional microRNA.

Therapeutic Effect of Injection-Acupuncture with Bee-Venom (Apitoxin) in Cases of Canine Otitis Externa

  • Kim, Sang-Hun;Jun, Hyung-Kyou;Kim, Suk;You, Myung-Jo;Jun, Moo-Hyung;Kim, Duck-Hwan
    • Journal of Veterinary Clinics
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    • v.25 no.3
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    • pp.159-164
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    • 2008
  • This study was carried out to determine the therapeutic effect of injection-acupuncture (AP) with bee-venom (apitoxin) in cases of canine otitis externa (COE). Fifteen dogs with naturally-acquired otitis externa were used in this study. The dogs were divided into the following antibiotics group (control group), apitoxin group (experimental group A) and apitoxin combined with antibiotics group (experimental group B). All groups were treated by ear cleaning with normal saline once on day 1. The control group was treated with susceptible antibiotics, and experimental group A was given injection-AP with apitoxin $(100{\mu}g/head)$ at TH17 (Yi Feng), SI19 (Ting Gong), GB03 (Shang Guan) and TH03 (Zhong Zhu) bilaterally. Experimental group B was treated with susceptible antibiotics and injection-AP with apitoxin at the same acupoints as experimental group A. All the groups were treated 3 times/week for 2 weeks. The identity of the causative agents, the changes in the clinical signs, otoscopic findings, bacterial count in the auricular discharges, and total WBC counts and neutrophil/lymphocyte (N/L) ratio in the peripheral blood were investigated in all groups. In bacterial isolation, Staphylococcus spp. combined with Streptococcus spp. was detected higher than other agents. The bacterial cell count in experimental group A was significantly decreased at 2 weeks (p<0.01), and those in experimental group B was significantly decreased at 1 week (p<0.01) and 2 weeks (p<0.01) compared by those of control group, respectively. The changes of clinical score in experimental group B were significantly decreased at 2 weeks (p<0.01) compared by those of control group, but, those of experimental group A was similar to those of control group. The changes of total WBC counts and neutrophil/lymphocyte (N/L) ratio were no significant difference found. In conclusion, injection-AP with apitoxin is an effective treatment for COE and might be an alternative method for treating COE.

Antagonistic inhibitory effects of probiotics against pathogenic microorganisms in vitro (Probiotics의 병원성미생물에 대한 길항적 억제효과)

  • Yuk, Young Sam;Lee, Young ki;Kim, Ga-Yeon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.12
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    • pp.110-116
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    • 2019
  • To investigate the antagonistic inhibitory effects in a mixed culture between probiotics and various pathogenic microorganisms, 140 probiotics were identified using a 16 rRNA sequencing phylogenetic analysis method, and various probiotics strains were isolated from Korean kimchi from January to December 2016. The antagonistic inhibition test of a mixed culture of four probiotics (Enterococcus faecalis, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri) with excellent antimicrobial activity and six pathogenic microorganisms (Candida albicans, Salmonella Enteritidis, E. coli O157:H7, Shigella flexneri, Staphylococcus aureus, and Pseudomonas aeruginosa)showed that the growth of most probiotics strains increased normally after culture, but growth was inhibited almost completely in most pathogenic microorganisms, except for S. Enteritidis. This antagonistic inhibitory effect in vitro was attributed to the low pH of the lactic acid and organic acid produced during fermentation. As a result, four probiotics strains isolated from Korean Kimchi are very likely to be developed as therapeutic agents for female yeast infections and colon and skin care. In the future, these therapeutic agents will help improve public health related to probiotics.

The Difference of Efficacy for Oral Hypoglysemic Pharmacotherapy Based on Sasang Constitutional Medicine Among Type II Diabetes Mellitus Patients in Korea (제 2형 당뇨병 환자에서 사상체질에 따른 경구 혈당강하요법의 치료 반응성 및 사용 패턴 평가)

  • Kim, Ji Yeon;Lee, Myung Koo;Kim, Jung Tae;Lim, Sung Cil
    • YAKHAK HOEJI
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    • v.58 no.1
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    • pp.71-79
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    • 2014
  • Although Korean patients with type 2 diabetes mellitus (T2DM) are generally treated by western medicine, many of them strongly believe in the traditional oriental Sasang constitutional classification and depend on it for food, health supplements, and oriental medicines decision making. Sasang constitutional classification is a part of traditional Korean medicine that divides people into four constitutional types (Tae-Yang: TY, Tae-Eum: TE, So-Yang: SY, and So-Eum: SE), which differ in inherited characteristics such as appearance, personality traits, susceptibility to diseases, and drug responses. It is recommended for T2DM patients to control their blood glucose very well from early stages with drugs and diet. However, many T2DM patients respond differently to their drugs, even though they receive the same medicine. Therefore, the present study investigated whether Sasang constitutional type can explain the therapeutic differences between oral hypoglycemic agents (OHAs) therapy (mono, dual and triple drug therapy). Patients of 618 with T2DM diagnosis and Sasang constitutional type known who received both western and oriental medicine treatment in a hospital between April 2006 and April 2013 retrospectively studied. HbA1c (%) and blood glucose (mg/dl) levels before OHAs therapy and 3 month after were collected for metformin (MET) or sulfonylurea (SU) monotherapy, MET+SU dual therapy, MET+except SU (where was either alpha-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor, meglitinide or thiazolidinedione) dual therapy, and triple therapy, according to Sasang constitutional type. For statistical analysis, ANOVA was used and paired t-test by SPSS 19.0 where P values less than 0.05 were considered statistically significant. Pattern was similar levels of HbA1c and blood glucose and which was decreased in order of mono, MET+SU dual, MET+except SU dual and triple therapy. In all patients comparison, for the So-yang (SY) constitutional type, either monotherapy was less effective; for Te-eum (TE) type, MET+SU dual therapy was less effective while MET+except SU dual therapy was more effective and the triple therapy was less effective; and for So-eum (SE) type, the triple therapy was more effective. For the management of TE type it is recommended to use drugs except SU when dual therapy is needed, restrict triple therapy and consider dual and insulin therapy; for SY type it is recommended to follow current guidelines; and for SE type it is advisable to skip dual therapy and start the triple therapy early. Finally, the therapeutic response to OHAs is different among Korean T2DM patients with different Sasang constitutional types. Taken together, the choice of effective OHAs therapy for each type is necessary in order to minimize the poor control of blood glucose level, the risk of complications, and the costs from a failure of therapy.