Synergistic Improvement in Insulin Resistance with a Combination of Fenofibrate and Rosiglitazone in Obese Type 2 Diabetic Mice

Choi, Woon-Seok,Lee, Jung-Jin,Kim, Yo-Han,Kim, In-Su,Zhang, Wei-Yun,Myung, Chang-Seon 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.4

Peroxisome proliferator-activated receptor (PPAR) ${\alpha}$, which is abundant in the liver, increases lipoprotein lipase activity, resulting in a decrease of triglyceride (TG) levels. $PPAR{\gamma}$, which is abundant in adipose tissue, stimulates adipocyte differentiation and adipogenesis, and results in an increase in insulin sensitivity. Fenofibrate, a $PPAR{\alpha}$ agonist, is commonly used to treat dyslipidemia, and rosiglitazone, a $PPAR{\gamma}$ agonist, is effective in improving glycemic control. To examine the synergistic effects of rosiglitazone in combination with fenofibrate, an obese type 2 diabetes mellitus (DM) mouse model was established by the combined administration of streptozotocin and nicotinamide and fed on a high-fat diet (35% of energy as fat) for 3 weeks. The mice had significantly higher plasma glucose concentrations and insulin resistance, as examined by an oral glucose tolerance test and insulin challenge test compared with normal mice. After establishing a dose-response curve for each drug, the drugs were orally administered for 3 weeks either alone or in combination. After individual administration of fenofibrate, HDL cholesterol levels significantly increased, and plasma glucose and TG levels decreased in obese type 2 DM mice. The individual administration of rosiglitazone showed increased insulin resistance (QUICKI). However, HDL cholesterol and TG levels were not significantly changed. In a combination of fenofibrate at 25 mg/kg and rosiglitazone at 1.25 mg/kg there was a decrease in plasma glucose and TG levels, and a combination of fenofibrate at 50 mg/kg and rosiglitazone at 2.5 mg/kg showed an increase in plasma HDL cholesterol levels. Moreover, parameters related to insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were improved significantly. Thus, our results show that combination therapy with lower doses of fenofibrate and rosiglitazone ameliorates the type 2 DM condition to a greater extent than high doses of either individual monotherapy.

Electro-hyperthermia up-regulates tumour suppressor Septin 4 to induce apoptotic cell death in hepatocellular carcinoma

Jeon, Tae-Won,Yang, Heebum,Lee, Chang Geol,Oh, Sang Taek,Seo, Daekwan,Baik, In Hye,Lee, Eun Hye,Yun, Ina,Park, Kyung Ran,Lee, Yun-Han Informa UK (TaylorFrancis) 2016 International journal of hyperthermia Vol.32 No.6

<P>Purpose: Modulated electro-hyperthermia (mEHT) has been shown to be effective against various types of human tumours, including hepatocellular carcinoma (HCC). Here we aimed to investigate the molecular mechanism underlying the cytotoxic effects of mEHT to HCC cells. Materials and methods: Human liver cancer cell lines, Huh7 and HepG2, were treated with mEHT (42 degrees C/60 min) three times at 2-day intervals. Growth inhibition and apoptotic induction were evaluated using MTS, microscopic analysis, a clonogenic assay, annexin V/PI staining and a ccK18 ELISA. Global changes in gene expression were examined using RNA sequencing to obtain insights into molecular changes in response to mEHT. For in vivo evaluation of mEHT we used HepG2 HCC xenografts grown in nude mice. Results: mEHT suppressed HCC cell proliferation and long-term colony formation through induction of apoptosis. The growth inhibitory effects are induced through a subset of molecular changes. Notably the expression level of septin 4 (SEPT4) (involved in pro-apoptotic activity and growth suppression) was up-regulated, whereas a key regulator of invasiveness G-Protein coupled receptor 64 (GPR64) was repressed. Subsequent Western blotting confirmed that the common increase in tumour suppressor SEPT4 in both Huh7 and HepG2 cells is accompanied by the restoration of cyclin-dependent kinase (CDK) inhibitor p21 and decrease in pro-caspase 7 and pro-caspase 3, thereby accelerating apoptotic signalling in HCC cells. Additionally, mEHT significantly inhibited the growth of human HCC xenografts in nude mice. Conclusions: These findings suggest that apoptotic cell death induced by mEHT is mediated by the up-regulation of tumour suppressor SEPT4 in human HCC cells.</P>

토끼에서 enrofloxacin과 enrofloxacin acetate의 比較藥物動態學

윤효인,박승춘,김창식,김민규,최기섭,신광순,박종일,조준형,조명행 충남대학교 수의과대학 동물의과학연구소 1996 動物醫科學硏究誌 Vol.4 No.-

This study was designed to examine the in vitro antibacterial activities and pharmacokinetics of enrofloxacin acetate (ENFXA) and enrofloxacin (ENFX). Two enrofloxacins had wide spectrum antibacterial activities against Gram positive and negative bacteria, and mycoplasma, showing potent antibacterial activities with low MICs (0.05-3.33 ㎍/㎖ for Gram positives, 0.002 ㎍/㎖ for Gram negatives and 0.02 ㎍/㎖ for mycoplasma). In order to investigate the profiles of two formulations of enrofloxacin we studied comparative pharmacokinetics of them in rabbits. Five rabbits were given 5 ㎎/㎏ body weight of each enrofloxacin formulation intravenously (i.v.) and orally (p.o.) in a cross-over study. Pharmacokinetic parameters of both formulations were calculated by the use of PCNONLIN, a computer program. Their bioavailibility in rabbits, the means of the area under the curve (AUC). After oral administration of each formulation in rabbits, the mean elimination half-lives (t_1/2,ke) were 3.25h (ENFX) and 4.32 h (ENFXA), and mean AUC 4.27 ㎍·h/㎖ (ENFX) and 6.21 ㎍·h/㎖ (ENFXA). Both enrofloxacin formulations seemed to have good tissue distribution and penetration as indicated by large volume of distribution: 4.76 1/㎏ for ENFX and 7.23 1/㎏ for ENFXA. With the results obtained in this study, ENFXA could be used in place of ENFX in rabbits.

Early Percutaneous Catheter Drainage Reduces Hospital Stay but Not Mortality in Patients with Pyogenic Liver Abscess

( Chang Hun Lee ),( Yun Chae Lee ),( Jaehee Park ),( Song Yi Yu ),( Hun Gil Jo ),( Jae Sun Song ),( Gum Mo Jung ),( Yong Keun Cho ),( Eun Young Cho ),( In Hee Kim ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: To investigate the factors associated with prolonged hospital stay and mortality among patients with pyogenic liver abscess (PLA) who underwent percutaneous drainage (PCD). Methods: We retrospectively reviewed data from PLA patients admitted from 2005 to 2018 at three tertiary hospitals in Jeonbuk province. We selected patients who underwent PCD during the admission period and early PCD was defined whether the procedure was done within 3 days of admission. Results: Among 655 patients diagnosed with PLA, 366 patients who underwent PCD were enrolled for the study. The patients had a mean age of 65.5 ± 14.7 years, and mean maximal diameter of the hepatic abscess was 6.1 ± 2.6 cm and 71.9% of the lesion was single. Next, two groups were divided depending on the time period of PCD and 269 patients (73.5%) underwent PCD within 3 days of hospitalization. In baseline characteristics, early PCD group was significantly higher in the number of abscess as well as the maximal abscess diameter. However, hospitalization period was significantly lower in the early PCD group though in-hospital mortality was not different. We checked laboratory results at 1 week after the admission and CRP levels were significantly lower in the early PCD group. We further analyzed the factors related to the long-term hospitalization more than 14 days. In multivariate analysis, underlying diabetes, lower albumin levels, and PCD inserted after 3 days of admission were independent factors associated with prolonged hospital stay. Conclusions: Early PCD facilitated improvement of inflammatory laboratory markers and shortened the hospital stay. Early PCD may be beneficial in patients with PLA.

백서에서 Depulpin®과 Formocresol에 대한 치수와 치근단 조직의 반응

문형인,김선호,황윤찬,오병주,황인남,김선헌,정선와,윤창,오원만 大韓齒科保存學會 2002 Restorative Dentistry & Endodontics Vol.27 No.4

One fifth dilution of formocresol is usually for pulpotomy of the primary teeth and emergency pulpotomy of the permanent teeth. However, the use of formaldehyde has been subjected to criticism because it may be absorbed into the blood stream and become distributed systemically, it may also alter the pulp tissue rendering it immumologically active, and have carcinogenic potential. Recently Depulpin®(VoCo., Germany) gains popularity as a devitalizing agent during root canal therapy in spite of high concentration of 49% paraformaldehyde because it facilitate devitalization of pulp and make root canal therapy easier. But there have been not enough publications about the reaction of pulp and periapical tissue caused by Depulpin. This study was performed to evaluate the histological changes in pulp and periapical tissue of rats after pulpotomy using formocresol and Depulpin and to elucidate the toxic effects of these agents. Thirty six Sprague-Dawley rats were anesthetized by intraperitoneal injection of ketamine. Maxillary first molar teeth were used for pulpotomy with formocresol and Depulpin. Rats were sacrificed after 2 days, 4 days, 1 week, 2 weeks, 3 weeks and 4 weeks respectively. Specimens were histologically observed by light microscope changes in pulp and periapical tissue. The obtained results were as follows. 1. Formocresol group A zone of fixed tissue, in which odontoblasts could clearly be defined, was present directly underneath the pulpotomy dressing in almost all teeth of this group. This was followed by an area of necrotic tissue which resembled dried out fibrous tissue with no cellular detail except some pyknotic nuclei. In the specimens of after 2 days, 4 days, 1 week, 2 weeks in which vital tissue was present. it was separated from the fibrous area by a zone of inflammation. In the specimens of after 3 weeks and after 4 weeks, inflammatory infiltrate was in the periodontal ligament adjacent to the apical foramina of the teeth. 2. Depulpin® group The area of necrotic tissue which had no cells and fibers , was present adjacent to the dressing. This was followed by dried out fibrous tissue with no cellular details except some pyknotic nucleli. A short stump of vital pulp with odontoblasts was present at the end of the canal after 2 days. Inflammatory infiltrate was in the periodontal ligament after 4 days and after 1week. Severe root resorption and necrosis of periapical tissue opposite the root resorption site were defined after 2 weeks and after 3 weeks. Periapical lesion which consist of necrotic tissue surrounded by a fibrous connective wall. was found after 4 weeks. The results indicated that Depulpin can cause more adverse reaction to the dental pulp and periapical tissue than formocresol, and further studies are needed for its clinical use with safety.

기아시 버들치 Rhynchocypris oxycephalus(Sauvage and Dabry)의 일부 영양조건에서의 효과 : 2. 체 절단면 계측형질의 변화 2. Characteristics of the Morphometric Changes in the Sectioned Body

박인석,임재현,정창화,노재구,김윤해,이영호 한국어류학회 2002 韓國魚類學會誌 Vol.14 No.1

버들치 Rhynchocypris oxycephalus(Sauvage and Dabry) 기아시의 영양 상태 평가를 위하여 비만도, 내장괴지수, dreessing 비를 비롯한 체 횡단 절단면에서의 형태적 변화를 조사였다. 9주간의 기아시 비만도, 내장괴지수 및 대부분의 체 횡단 절단면 계측 형질들에서의 감소를 보였다(P<0.05). 본 연구 결과, 실험에 적용된 영양성 parameter는 본 종의 영양 상태 파악에 유용한 지표임을 시사한다. 연구 결과를 자세히 해석하여, 버들치에서의 주요 체 절단 형질의 산업성을 논의하였다. The effects of starvation on the morphometrical changes in sectioned body traits, condition factor, viscera index and dressing percentage were determined for evaluating nutritional conditions of Rhynchocypris oxycephalus(Sauvage and Dabry). Starvation for nine weeks resulted in a decrease in most sectioned traits as well as in condition factor and viscera index(P<0.05). These findings suggest that nutritional parameters used in this study appear to be a useful index for nutritional status in this species. The data has been interpreted in detail and some important body sectioned values of interest to commercial growers discussed.

쌀 품종별 제분특성 및 제빵적성에 관한 연구

유인수,허장성,윤인화 단국대학교 1998 論文集 Vol.33 No.-

This experiment was conducted to evaluate the characteristics of extruded rice flour, bread qualities of rice flour in blends with wheat flour and properties of the steam cooked rice bread for Korean rice varieties compared to the imported rice. Whiteness index and contents of crude fat and crude protein were higher in Korean rice varieties than in the imported rice, but the content of amylose was less than 20 percent in Korea varietes. Bread qualities score according to the 30% composition ratio of the extruded rice flour to wheat flour was inferior to the bread with only wheat flour in texture and color, but it was better in taste. Bread quality for rice varieties were good in order of Dongjinbyeo>Calrose>Dasanbyeo>Indian rice Panticle size of over 100 mesh was more in rice flour from the wet roller mill compare to the dry-pin mill in grinding methods. In amylogram characteristics, gelatinization temperature, peak viscosity, final viscosity were lower in rice flour from in wet roller mill than from the dry-pin mill. In varieties, Dongjinbyeo and Dasanbyeo were good for bread-making properties with lower value in amylogram charateristics. In score of the volume, hardness and taste for the steam cooked rice bread, the flour from the wet roller mill was higher than that from the drip-pin mill. In varieties, it was in order of Dongjinbyeo>Dasanbyeo>Calrose>Indian rice.

흰쥐 시상하부에서의 Neuropeptide Y 신경분포에 관한 면역조직화학적 연구

김종중,장인엽,정주현,문정석,정윤영 朝鮮大學校 附設 醫學硏究所 1992 The Medical Journal of Chosun University Vol.17 No.1

The distributions of neuropeptideY(NPY) in the hypothalamus of the adult rat was investigated using indirect immunohistochemistry. The method was showed that neuropeptide Y had a widespread distributions and was present in extremely high concentration in the hypothalamic nuclei of the rat. A few number of NPY-containing perikarya was found in the paraventricular nucleus, medial to the fornix and the dorsomedial hypothalamic nucleus, also relatively many numbers was found in the arcuate nucleus in colchicine pretreated rat. Neuropeptide Y-immunoreactive axons and terminals in the hypothalamus were found in most hypothalamic nuclei. The highest concentrations of neuropeptide Y containing fibers were found in the arcuate nucleus, paraventricular nucleus, and also the supraoptic nucleus, dorsomedial hypothalamic nucleus, preoptic area showed relatively high concentration of neuropeptide Y-immunoreactive fibers. The extremely high concentations of neuro-peptide Y in the hypothalamus indicate important role in many brain functions.

수리된 복합레진 수복물의 전달결합강도 연구

최수영,정선와,황윤찬,김선호,윤창,오원만,황인남 大韓齒科保存學會 2002 Restorative Dentistry & Endodontics Vol.27 No.6

This study was performed to evaluate the interfacial shear bond strength of base (direct and indirect) and repair composites with aging and surface treatment methods. Direct composites resin specimens (Charisma®, Heraeus Kulzer, Germany) were aged for 5 min, 1 hour, 24 hours, and 1 week in 37℃ distilled water before surface treatment, and then divided into five groups: Group 1, grinding; Group 2, grinding and application of bonding agent; Group 3, grinding, etching with 37% phosphoric acid for 30sec, and application of bonding agent; Group 4, grinding, etching with 37% phosphoric acid for 30sec, silane treatment, and application of bonding agent; Group 5, grinding, etching with 4% hydrofluoric acid for 30sec, silane treatment, and application of bonding agent. Indirect composite resin specimens (Artglass®, Heraeus Kulzer, Germany) were aged for 1 week in 37℃ distilled water and divided into seven groups: Group 1 - Group 5, equal to Charisma specimens; Group 6, grinding, etching 37% phosphoric acid for 60sec, silane treatment, and application of bonding agent; Group 7, grinding, etching with 4% hydrofluoric acid for 60 sec, silane treatment, and application of bonding agent. The repair material(Charisma®) was then added on the center of the surface (5mm in diameter, 5mm in height). The shear bond strength was tested and the data was analyzed using one-way ANOVA and the Student-Newman-Keuls test. The following conclusions were drawn. 1. The shear bond strength of Charisma® specimens aged for 1 hour was significantly higher in Group 2 and Group 5 than in Group 1 (p<0.05), and that of Charisma® specimens aged for 1 week was significantly higher in Group 3 and Group 5 than in Group 1 (p<0.05). No significant difference was found in the bond strength of specimens aged for 5 min and 24 hours. 2. In Group 2 of the Charisma® specimens, there was significant difference between the bond strength of 24 hours and that of 1 week (p<0.05). 3. In Group 4 of the Charisma® specimens, the shear bond strength of specimens aged for 24 hours was significantly higher than the others(p<0.05). 4. There was no significant diiference between the shear bond strength of the Artglass® specimens. 5. Most of the Charisma® specimens showed cohesive fractures. Artglass® specimens that were etched with acid(phosphoric or hydrofluoric) for 30 sec showed more cohesive fractures.

심인성쇼크로 관상동맥 중재술 중 대동맥 내 풍선펌프 사용 시 임상 경과

이재필 ( Jae Pil Lee ),남창욱 ( Chang Wook Nam ),박정호 ( Jung Ho Park ),배종엽 ( Jong Yop Bae ),김인철 ( In Cheol Kim ),조윤경 ( Yun Kyeong Cho ),박형섭 ( Hyoung Sub Park ),윤혁준 ( Hyuck Jun Yoon ),김형섭 ( Hyungseop Kim ),허승 대한내과학회 2015 대한내과학회지 Vol.89 No.2

Background/Aims: The mortality of hospitalized patients undergoing treatment with an intra-aortic balloon pump (IABP) due to cardiogenic shock is well known as quite high. The aim of this study was to evaluate the outcome of percutaneous coronary intervention (PCI) with an IABP in patients with acute coronary syndrome (ACS) and cardiogenic shock and identify the predictors of in-hospital mortality. Methods: 134 patients who underwent PCI with IABP due to ACS complicated by cardiogenic shock were consecutively enrolled. Outcomes were obtained and analyzed during hospitalization and after 1 year. Results: The incidence of all-cause mortality was 35.8% (in-hospital mortality, 34.3%, 1-year mortality, 1.5%). The nonsurvival group exhibited higher peak levels of creatine kinase MB, lower ejection fractions, and higher incidences of ST elevation myocardial infarction, ventricular arrhythmia, and use of an assistive device than did the survival group. Aging (hazard ratio 2.839, 95% confidence interval 1.408-5.723, p = 0.004), the use of a temporary pacemaker (2.035, 1.114-3.720, 0.021), the use of a mechanical ventilator (4.376, 1.852-10.341, 0.001), and the performance of cardiopulmonary resuscitation (CPR) (2.219, 1.017-4.839, 0.045) were independent predictors for in-hospital mortality. However, out-of-hospital mortality among in-hospital survivors was not affected by predictors of in-hospital mortality. Conclusions: The incidence of in-hospital mortality was high, as expected in patients undergoing PCI with IABP due to ACS with cardiogenic shock. Aging, CPR, and additional procedures such as pacemaker use and mechanical ventilation were predictors of in-hospital mortality. However, the patients who were successfully discharged after the complex procedure showed acceptable 1-year outcomes. (Korean J Med 2015,89:186-191)