• Title/Summary/Keyword: 약제내성

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Clinical Evaluation of Surgical Resection of Pulmonary Tuberculosis (폐결핵에 대한 외과적 치험)

  • Park, Seung-Kyu;Shon, Mal-Hyun;Han, Dong-Gi;Ha, Hyun-Chul;Jin, Young-Ho;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.474-480
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    • 1995
  • Background: In spite of initial intensive and long-term chemotherapy for pulmonary tuberculosis, many problems remain in the treatment of the residual lesion. The role of surgical intervention for pulmonary tuberculosis is getting rid of such residual lesion of pulmonary tuberculosis to support the healing process and to induce bacteriologically negative conversion in the end. Method: We experienced 30 cases of pulmonary resection for pulmonary tuberculosis from Aug. 1994 through Apr. 1995 in National Masan Tuberculosis Hospital. We conducted retrospective study to analyze several variables for the cases. Results: 1) The ratio between male and female was 4:1(male 24, female 6) and the age of peak incidence was in 3rd and 4th decades. 2) Indications for pulmonary resection in the radiographic findings were cavitary lesions of 19 cases(63.3%), destroyed one side of 8 cases(26.7%) and destroyed one lobe of 3 cases(10%). 3) 16 of 20 cases with unilateral lesions and all of 10 cases with bilateral lesions on chest X-ray films showed AFB positive on preoperative sputum smears. 14 cases(87.5%) of unilateral lesions and 9 cases(90%) of bilateral ones were converted into AFB negative postoperatively. Negative conversion rates of pneumonectomy and lobectomy cases were 100% and 85.7%, respectively. 4) Preoperative combined disease was 3 cases(10%) of DM and postoperative complications were 2 cases(6.7%) of dead space and no death. Conclusion: Chemotherapy only has some limitation in treatment of all tuberculosis. So, surgical intervention for pulmonary tuberculosis is an effective method as partner of chemotherapy.

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Clinical Characteristics of Paradoxical Response to Chemotherapy in Pulmonary Tuberculosis (항결핵제 사용 중 폐병변의 일시적 악화를 보인 환자의 임상상)

  • Kim, Soo-Hee;Chung, Hyo-Young;Lee, Ghie-Dong;Shin, Min-Ghie;Jung, Tae-Sik;Jin, Byung-Cheol;Kim, Hyun-Jung;You, Jin-Jong;Lee, Jong-Deog;Hwang, Young-Sil
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.1
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    • pp.27-35
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    • 2002
  • Background : The paradoxical response refers to an enlargement of old lesions or unexpected new ones during apparently adequate antituberculous therapy. This response has been reported in cases of intracranial tuberculoma, tuberculous lymphadenopathy, tuberculous pleurisy and pulmonary tuberculosis. However, there are few reports on its frequency and clinical characteristics. Materials and Methods : This study enrolled 205 patients who were treated with first line antituberculous agents for more than 6 months. We retrospectively studied 155 patients with pulmonary tuberculosis and 57 patients with pleural tuberculosis (7 patients had both) from July 1998 to March 2000. The patients were divided into the paradoxical response group and the non-paradoxical group. The clinical characteristics of the paradoxical response group and the non-paradoxical group. The clinical characteristics of the paradoxical group were investigated. Statistical analysis was done with an independent sample T-test and Chi-squared test. Results : 29 of the 205 patients(14.1%) had paradoxical response. Among the 29 patients, there were 19 pulmonary tuberculosis, 8 tuberculous pleurisy(2 patients had both). Paradoxical response appeared 32 days (mean 35 days in pulmonary tuberculosis, mean 25 days in tuberculous pleurisy) after the beginning of chemotherapy. The duration to regress less than half of initial chest lesion was 114 days in pulmonary tuberculosis and 124 days in tuberculous pleurisy, respectively. Most common clinical manifestation of paradoxical response patients was coughing in both pulmonary tuberculosis and tuberculous pleurisy. Male sex, high blood WBC count and high level of pleural fluid LDH were related with paradoxical response. Conclusion : These findings suggest that presponse usually appears 1 month and disappears within 4 months after the beginning of anti-tuberculous chemotherapy. Paradoxical response was relatively correlated with male sex, high blood WBC count and high level of pleural fluid LDH.

Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells (미세소관-손상 항암제 처리에 의한 세포주기의 정지 및 에폽토시스 유도)

  • Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.26 no.3
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    • pp.376-386
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    • 2016
  • Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

A Fluctuation of Soil Microflora in Upland Soil Treated with Metalaxyl, Carbofuran and Simazine (Metalaxyl, Carbofuran, Simazine을 처리한 밭토양에서의 미생물수의 변동)

  • Lee, Wang-Hyu;Kim, Ju-Hee
    • Korean Journal of Environmental Agriculture
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    • v.17 no.3
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    • pp.220-226
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    • 1998
  • The effects of metalaxyl(granule), carbofuran(granule) and simazine(water soluble powder) on the soil microflora were conducted at field soil between Iksan and Chonju province. Pesticides were divided into 0.5, 1, 1.5 and 2.0 times of normal of field, respectively. The number of fluorescent Pseudomonas was ranged from $10^3$ to $10^6/g$ in both field soil treated with cabofuran. Pseudomonas concentration of Chonju field soil slowly increased and approached the maximum level at 56 day after treatment(DAT). It showed the higher at 14DAT than other DAT in Iksan field soil treated with metalaxyl or simazine, whereas it increased again at 112 DAT in metalaxyl treatment. Cabofuran treatment of both field soil showed maximum Pseudomonas number at 28 DAT compared to that of other treatments. In Chonju field soil, those Pseudomonads of metalaxyl and simazine treatment increased the highest level at 7 DAT. Simazine treatment decreased it's number from the beginning of experiment. In both soil, metalaxyl treatment decrease the general fungi number at 7 DAT, but increase at 14 and 56 DAT in Iksan field soil. However it increased at 56 DAT in Chonju field soil. Cabofuran treatment of Iksan field soil tended to decrease general fungi number at 28 DAT, but was ranged from 1.0 to $8.6{\times}104/g$ for the rest of experimental period. It started to increase at 56 DAT simazine treatment of Iksan. General bacterial concentration both soil treated with cabofuran was belong to $26.6{\sim}29.6{\times}106$. It was the highest at 56 DAT, but was not significantly different. General actinomyces number was highly increased at 7 and 112 DAT compared to that of other DAT. Pseudomonas putida or P. fluorescens from both field soil was separated and identified 10 to 30 of all 104 Pseudomonas, respectively. All isolated microorganisms showed chemical resistance of 100ppm metalaxyl, cabofuran and simazine treatment.

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The Adjuvant Effect of Subcutaneous Interferon-gamma in the Treatment of Refractory Multidrug-resistant Pulmonary Tuberculosis (난치성 다제내성 폐결핵에서 피하주사 Interferon-gamma 치료의 효과: 예비연구)

  • Kim, Eun Kyung;Shim, Tae Sun;Lee, Jung Yeon;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Dong Soon;Kim, Won Dong;Kim, Woo Sung
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.226-233
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    • 2004
  • Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

Clinical Characteristics of Tuberculosis in North Korean Refugees (북한이탈주민에서의 결핵의 임상적 고찰)

  • Choi, Chang-Min;Jeong, Woo-Kyoung;Kang, Cheol-In;Kim, Doh-Hyung;Kim, Young-Keun;Heo, Sang-Taek;Kim, Hee-Jin
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.3
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    • pp.285-289
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    • 2006
  • Background : North Korea's economic and public health problems began in the early 1990s as a result of the gradual loss of economic support from its communist allies, combined with an inordinate number of natural disasters. The decline in public health has increased the incidence of tuberculosis in North Koreans and refugees. This study investigated tuberculosis situation in North Korean refugees in order to prepare for the future impact of tuberculosis control in Korea. Material and Methods : From 2001 to 2005, tuberculosis patients among North Korean refugees who were diagnosed before or after arriving in South Korea, based on the official records of OO hospital, were enrolled in this study. The demographic and clinical data of the cases were evaluated retrospectively. Results : A total of 42 TB cases were reviewed during the study period. Of these, 37 (88.1%) cases were pulmonary TB. based on the cases identified among the number of North Korean refugees' arriving each year, the annual incidence of pulmonary TB were 900 per 100,000 in 2004, 700 in 2003, The number of smear-positive patients was 20 (47.6%) and the number of culture-positive patients was 18 (42.9%). Of the M. tuberculosis isolates, 2 cases were found to be susceptible to all anti-TB drugs available, 4 were resistant to isoniazid, and 3 were multi-drug resistant. Conclusion : The prevalence of pulmonary TB in North Korean Refugees is high. In addition, North Korean refugees suffer from more severe tuberculosis in bacteriological and radiological aspects.

Clinical Effects of Prothinoamide, Cycloserine, Para-Aminosalicylic Acid, Ofloxasine in Retreatment of Pulmonary Tuberculosis (폐결핵 재치료 환자에서 Prothionamide, Cycloserine, Paraminosalicylic acid, Ofloxasine을 이용한 경구 4제 요법의 임상 효과)

  • Hong, Jae-Rak;Yoo, Min-Kyu;Jeong, Jae-Man;Kim, Young-Jun;Son, Mal-Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.5
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    • pp.693-700
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    • 1996
  • Background : Antituberculous therapy is set a short-term therpy used isoniazid(INH), rifampin(RFP), ethambutol(EMB), pyrazinamide(PZA) from 1970s' and treatment rate has been very improved. But drug interruption or irregular medication due to side effects and resistance of drug are serious problem to retreatment cases, specially. Ofloxasine(OFX), developed from Quinolone at 1980's is effective not only other respiratory infectious disease but also pulmonary tube rculosis. And this is useful drug instead of injection agents for retreatment patients who have side effects to other drugs, lived far distance from medical clinics. So, we will evaluate theffectiveness as four oral drugs involving OFX. Method : A retrospective study was made through the regular follow up of smear positive cases,who treated by four drug, namely, prothionamide (PTA) cycloserine(CS), OFX, paraminosalicylic acid(pAS). Results: 1) Out of 66case with positive sputum AFB smear, 42(64%)cases achieved the negative conversion. 2) Considering the negative conversion in all group, 34 case (52%) of sputum conversion occured within first 6 months, on the extent of diease was minimal, moderate, far advanced pulmonary tuberculosis, sputum AFB smear negative response to treatment was 100%, 78%, 46% respectively. 3) The roentgenological improvement occured in 38(58%), extent of diease was minimal, moderately, far advanced pulmonary tuberculosis, Roentgenological improvement to retreatment was 75%, 64%, 46%. 4) When the drnation of patients illness was less than 1 year, 1 to 3 years, 3 10 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 100%, 88%, 80%, 52 %. 5) On side effects, major problems are gastrointestinal troubles, mild liver function abnormality, psychotic problemes, and skin problem(urticaria, itching sensation). Conclusion : The duration & extents of patients illness was shorter & minimal, sputum AFB smear negative response rate was better. Radiologic response is better as shorter duration and minimal extent of diease. But, as diease is longer duration & far advanced, sputum negative conversion & Roentgenological improvement is poor and limited. The adverse reaction was mainly observed gastrointestinal troubles(indigestion, abdominal pain, nausea, vomiting, diarrhea) and are well controled by symptomatic management in most patients, as regard to tolerance to the secondary drugs.

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Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

해조류 첨가사료가 돌돔의 성장과 면역기능에 미치는 영향

  • 김병기;원경미;유병서
    • Proceedings of the Korean Aquaculture Society Conference
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    • 2003.10a
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    • pp.80-81
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    • 2003
  • 양식 생물의 질병 제어는 예방과 치료를 통해 이루어진다. 그러나 항생제의 오ㆍ남용으로 인하여 약제 내성균의 증가와 치료 효과가 감소하고, 나아가 식품안전성 문제로 양식생물의 소비를 위축시켜왔다. 따라서 질병이 발생한 후에 시행하는 화학약품 치료법은 이미 한계에 달하였다. 이에 따라 사전에 질병을 차단하는 예방법인 vaccine이나 질병에 대한 저항능력을 키우는 비특이적 면역 증강물질에 대한 관심이 꾸준히 높아지고 있다. 해조류에는 다량의 lectin이 포함되어 있는데, Lectin은 당에 결합하는 단백질의 총체적인 이름으로, defence molecule로 작용하여 어류가 섭취할 경우 외래 항원으로 인식하여 지속적으로 면역 기능을 활성화시키는 것으로 알려져 있다. 따라서 본 연구는 돌돔사료에 kelf meal을 첨가하여 공급한 후 이들의 성장과 비특이적 면역기구에 미치는 효과를 조사하였다. 실험사료는 상업용 kelf meal을 0%, 2%, 5% 첨가하고, 2반복으로 500L FRP 탱크에서 8주간 사육하였다. 실험어류는 40g 내외의 돌돔을 대상으로 하였고, 사료공급 4주 및 8주에 각 실험구의 돌돔을 대상으로 비특이적 면역기구에 미치는 효과를 조사하였다. 체액성 면역 조사로는 혈청 및 점액 lysozyme 활성과 Escherichia coli에 대한 혈청 내 보체의 살균 능력을 조사하였고, 세포성 면역 조사는 전신 식세포의 NBT 환원 실험과 말초혈액의 식세포 식균능을 측정하였다. 식균능 시험은 Escherichia coli FKC (formalin killed cell)에 대한 식균율 및 식균지수로 나타내었다. 나아가 돌돔 말초혈액의 혈구조성에 미치는 영향을 조사하기 위하여 적혈구 5,000 세포당 임파구, 전구, 호중구의 수를 계수하였다. 8주간의 사육결과 사료계수는 각각 1.20, 1.25, 1.42로 대조구와 2% 첨가구는 큰 차이가 없었으나, 5% 첨가구는 나빠지는 경향을 보였다. 사료섭취량은 kelf meal의 첨가량이 늘어나면서 감소하는 경향이었다. 비특이적인 면역 기구에 대한 자극 효과는 체액성 면역의 지표로 측정한 lysozyme의 활성도는 혈청과 점액 모두에서 대조구보다 실험구에서 활성이 높았고, 혈청 lysozyme 활성은 5% 첨가구에서 가장 높았다. 혈청 내 보체의 살균능은 실험구간 차이가 없었다. 세포성 면역의 지표로 측정한 전신 식세포의 $O_2$ 생성능(NBT 환원능)은 5% 첨가구에서 가장 높았다. 말초 혈액의 식균능은 식균율과 식균지수 모두 실험구에서 높았고, 특히 5% 첨가구에서 가장 높았다. 말초 혈액 혈구조성의 변화는 임파구와 전구의 경우 실험구에서 높았으나 호중구에서는 차이가 없었다. 이상의 결과, 양식 돌돔에 kelf meal을 2% 첨가하는 것이 사료계수에 큰 영향을 미치지 않고, 돌돔의 체액성 및 세포성 면역을 적절히 자극하는 것으로 나타나, 돌돔의 기능성 사료 첨가물로서 이용 효과가 있을 것으로 기대된다.

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A Review of Sirtuin Inhibitors in Therapeutics, Pharmaceutics, and Plant Research (치료제, 조제학 및 식물을 위한 서투인 억제제의 유용성)

  • Lee, Yew
    • Journal of Life Science
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    • v.30 no.1
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    • pp.96-105
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    • 2020
  • Sirtuin inhibitors are pharmaceutically and therapeutically valuable compounds that inhibit sirtuin, a type III histone deacetylase. Synthetic sirtuin inhibitors were discovered and characterized using cell-based screens in yeast (Saccharomyces cerevisiae) and have been used in the study of aging, carcinogenesis, and diabetes, all of which are related to sirtuin function. For medical applications, synthetic inhibitors have been further developed for increased potency and specificity, including compounds containing nicotinamide, thioacetyl lysine, β-naphthol, and indole derivatives. Suramin, tenovin, and their analogues were developed as a result. Sirtuin inhibitors were found to affect organic development and have been used to genetically modify plants, although a sirtinol-resistant mutation in the biosynthesis of a molybdopterin cofactor for an aldehyde oxidase has been identified. Some natural flavonoids, and catechin and quercetin derivatives also act as sirtuin inhibitors have been studied to identify a more potent inhibitor for therapeutic purposes. In this review, sirtuin is introduced and the therapeutic inhibitors that have been developed are presented, particularly sirtinol which has been used for genetic modification in plants though it was not designed to be so. Sirtuin inhibitors with greater potency and selectivity are required and those developed in pharmaceutics should be used in plant research to identify more authentic sirtuins in plants.