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( Sook Jin Seong ),( Young Ran Yoon ),( Mi Sun Lim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Te1misartan is an angiotensin II receptor antagonist and chlorthalidone is a thiazide-like diuret-ics. In this study, we report serious adverse events (SAEs) during clinical trial for pharmacokinetic interaction between telmisartan and chlorthalidone in healthy Korean subjects. Two separate, ran-domized, multiple-dose, two-period, one-sequence studies were conducted at Kyungpook National University Hospital. In part A, 43 volunteers received telmisartan for 7 days, and then chlorthali-done for 14 days (days 8-21). Telrnisartan was co-administered during day 15-21 to evaluate the effects of chlorthalidone on the pharmacokinetics of telmisartan at steady state. A healthy 36-year-old male in part A was referred to the emergency room due to severe nausea and vomiting developed about 3 h after administration of chlorthalidone on day 9. Hypokalemia and QT prolongation were observed during his initial laboratory examination and electrocardiogram (ECG) monitoring in the emergency wilt. Nausea and vomiting improved after conservative management with hos-pitalization for 9 days. We consider that the episodes of excessive nausea and vomiting resulted in hypokalemic state which was potentiated by chlorthalidone. And the hypokalemic state caused the lengthening of the QT interval on ECG.
Lim, Ae Ran,Jeong, Se-Young IOP Pub 2006 Journal of Physics, Condensed Matter Vol.18 No.29
<P><I>T</I><SUB>1</SUB>, <I>T</I><SUB>1ρ</SUB> and <I>T</I><SUB>2</SUB> for the <SUP>1</SUP>H and <SUP>2</SUP>H nuclei in (NH<SUB>4</SUB>)<SUB>3</SUB>H(SO<SUB>4</SUB>)<SUB>2</SUB> and (ND<SUB>4</SUB>)<SUB>3</SUB>D(SO<SUB>4</SUB>)<SUB>2</SUB> single crystals grown using the slow evaporation method were measured for phases I, II, III, IV and V. The <SUP>1</SUP>H <I>T</I><SUB>1</SUB>, <I>T</I><SUB>1ρ</SUB>, and <I>T</I><SUB>2</SUB> values were found to exhibit different trends in phases II and III: <I>T</I><SUB>1</SUB>, <I>T</I><SUB>1ρ</SUB> and <I>T</I><SUB>2</SUB> for <SUP>1</SUP>H do not change significantly near the phase transition at 265 K, whereas near 413 K they change discontinuously. We conclude that the NH<SUB>4</SUB><SUP>+</SUP> and H(SO<SUB>4</SUB>)<SUB>2</SUB><SUP>−</SUP> ions do not play an important role in the III–II phase transition, but do play important roles in the II–I phase transition. The liquid-like nature of the <SUP>1</SUP>H <I>T</I><SUB>1ρ</SUB> and <I>T</I><SUB>2</SUB> above 413 K is indicative of the destruction and reconstruction of hydrogen bonds. Moreover, the phase transitions of the (NH<SUB>4</SUB>)<SUB>3</SUB>H(SO<SUB>4</SUB>)<SUB>2</SUB> crystal are accompanied by changes in the molecular motion of the (NH<SUB>4</SUB>)<SUP>+</SUP> ions. The variations with temperature of the <SUP>2</SUP>H <I>T</I><SUB>1</SUB> and <I>T</I><SUB>2</SUB> of (ND<SUB>4</SUB>)<SUB>3</SUB>D(SO<SUB>4</SUB>)<SUB>2</SUB> crystals are not similar to those observed for the <SUP>1</SUP>H <I>T</I><SUB>1</SUB> and <I>T</I><SUB>2</SUB>. Our comparison of the results for (NH<SUB>4</SUB>)<SUB>3</SUB>H(SO<SUB>4</SUB>)<SUB>2</SUB> and (ND<SUB>4</SUB>)<SUB>3</SUB>D(SO<SUB>4</SUB>)<SUB>2</SUB> crystals indicates the following: the <SUP>1</SUP>H <I>T</I><SUB>1ρ</SUB> and <I>T</I><SUB>2</SUB> of the (NH<SUB>4</SUB>)<SUP>+</SUP> and H(SO<SUB>4</SUB>)<SUB>2</SUB><SUP>−</SUP> ions above <I>T</I><SUB>C1</SUB> are characteristic of fast, liquid-like motion, which is not the case for (ND<SUB>4</SUB>)<SUB>3</SUB>D(SO<SUB>4</SUB>)<SUB>2</SUB>; and the <SUP>2</SUP>H <I>T</I><SUB>1</SUB> of D(SO<SUB>4</SUB>)<SUB>2</SUB><SUP>−</SUP> in (ND<SUB>4</SUB>)<SUB>3</SUB>D(SO<SUB>4</SUB>)<SUB>2</SUB> is longer than the <SUP>2</SUP>H <I>T</I><SUB>1</SUB> of (ND<SUB>4</SUB>)<SUP>+</SUP> in contrast to the results for (NH<SUB>4</SUB>)<SUB>3</SUB>H(SO<SUB>4</SUB>)<SUB>2</SUB> crystals.</P>
Lim, Young-Ran,Han, Songhee,Kim, Joo-Hwan,Park, Hyoung-Goo,Lee, Ga-Young,Le, Thien-Kim,Yun, Chul-Ho,Kim, Donghak The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.2
Streptomyces avermitilis produces clinically useful drugs such as avermectins and oligomycins. Its genome contains approximately 33 cytochrome P450 genes and they seem to play important roles in the biosynthesis of many secondary metabolites. The SAV_7130 gene from S. avermitilis encodes CYP158A3. The amino acid sequence of this enzyme has high similarity with that of CYP158A2, a biflaviolin synthase from S. coelicolor A3(2). Recombinant S. avermitilis CYP158A3 was heterologously expressed and purified. It exhibited the typical P450 Soret peak at 447 nm in the reduced CO-bound form. Type I binding spectral changes were observed when CYP158A3 was titrated with myristic acid; however, no oxidative product was formed. An analog of flaviolin, 2-hydroxynaphthoquinone (2-OH NQ) displayed similar type I binding upon titration with purified CYP158A3. It underwent an enzymatic reaction forming dimerized product. A homology model of CYP158A3 was superimposed with the structure of CYP158A2, and the majority of structural elements aligned. These results suggest that CYP158A3 might be an orthologue of biflaviolin synthase, catalyzing C-C coupling reactions during pigment biosynthesis in S. avermitilis.
Lim, Soo Young,Kang, Ji Hoon,Jung, Mi Ran,Ryu, Seong Yeob,Jeong, Oh The Korean Gastric Cancer Association 2020 Journal of gastric cancer Vol.20 No.4
Purpose: The role of prophylactic abdominal drainage in total gastrectomy is not well-established. This study aimed to evaluate the efficacy of abdominal drainage in the prevention and management of major intra-abdominal complications after total gastrectomy for gastric carcinoma. Materials and Methods: We retrospectively reviewed the data of 499 patients who underwent total gastrectomy for gastric carcinoma in a high-volume institution. The patients were divided into drainage and non-drainage groups and compared for the development and management of major intra-abdominal complications, including anastomotic leak, abdominal bleeding, abdominal infection, and pancreatic fistulas. Results: The drainage group included 388 patients and the non-drainage group included 111 patients. The 2 groups showed no significant differences in clinicopathological characteristics or operative procedures, except for more frequent D2 lymphadenectomies in the drainage group. After surgery, the overall morbidity (drainage group vs. non-drainage group: 24.7% vs. 28.8%, P=0.385) and incidence of major intra-abdominal complications (6.4% vs. 6.3%, P=0.959) did not significantly differ between the two groups. The non-drainage group showed no significant increase in the incidence rate of major intra-abdominal complications in the subgroups divided by age, sex, comorbidity, operative approach, body mass index, extent of lymphadenectomy, and pathological stage. Abdominal drainage had no significant impact on early diagnosis, secondary intervention or reoperation, or recovery from major intra-abdominal complications. Conclusions: Prophylactic abdominal drainage showed little demonstrable benefit in the prevention and management of major intra-abdominal complications of total gastrectomy for gastric carcinoma.
Evaluation of the Neurological Safety of Epidural Milnacipran in Rats
Lim, Seung-Mo,Shin, Mee-Ran,Kang, Kyung-Ho,Kang, Hyun,Nahm, Francis Sahn-Gun,Kim, Baek-Hui,Shin, Hwa-Yong,Lim, Young-Jin,Lee, Sang-Chul The Korean Pain Society 2012 The Korean Journal of Pain Vol.25 No.4
Background: Milnacipran is a balanced serotonin norepinephrine reuptake inhibitor with minimal side effects and broad safety margin. It acts primarily on the descending inhibitory pain pathway in brain and spinal cord. In many animal studies, intrathecal administration of milnacipran is effective in neuropathic pain management. However, there is no study for the neurological safety of milnacipran when it is administered neuraxially. This study examined the neurotoxicity of epidural milnacipran by observing behavioral and sensory-motor changes with histopathological examinations of spinal cords in rats. Methods: Sixty rats were divided into 3 groups, with each group receiving epidural administration of either 0.3 ml (3 mg) of milnacipran (group M, n = 20), 0.3 ml of 40% alcohol (group A, n = 20), or 0.3 ml of normal saline (group S, n = 20). Results: There were no abnormal changes in the behavioral, sensory-motor, or histopathological findings in all rats of groups M and S over a 3-week observation period, whereas all rats in group A had abnormal changes. Conclusions: Based on these findings, the direct epidural administration of milnacipran in rats did not present any evidence of neurotoxicity in behavioral, sensory-motor and histopathological evaluations.