• Journal of Genetic Medicine
• /
• 제13권2호
• /
• pp.72-77
• /
• 2016

Purpose: Gaucher disease (GD) is the most common lysosomal storage disease caused by beta-glucocerebrosidase (GBA) deficiency. Oral substrate reduction therapy with miglustat ($Zavesca^{(R)}$) was approved for the treatment of adults with GD type 1, for whom enzyme replacement therapy (ERT) is unsuitable or not a therapeutic option. In this study, we report the effect of miglustat ($Zavesca^{(R)}$) in three Korean GD patients. Materials and Methods: Clinical findings comprising age at diagnosis, presenting signs, laboratory findings at diagnosis, GBA activity and mutations, and clinical courses of the three patients were reviewed. Results: Miglustat was administered to three patients who reported allergic reactions during intravenous imiglucerase infusions. One patient withdrew after 15 months of miglustat administration owing to continuous elevation of disease biomarker levels (chitotriosidase, acid phosphatase, and angiotensin-converting enzyme). Poor adherence to medication was suspected but was denied by the patient. In the other two patients, platelet count and levels of hemoglobin and other biomarkers remained stable during miglustat administration. However, they suffered from severe diarrhea and weight loss, which led to miglustat discontinuation after 1 and 12 months of administration. Conclusion: Our study shows that although miglustat is suggested to GD patients as an alternative treatment to ERT, significant adverse reactions may lead to discontinuation of miglustat. In addition, it is difficult to monitor the drug adherence.

• Journal of Pharmaceutical Investigation
• /
• 제34권2호
• /
• pp.115-123
• /
• 2004

Geniposide and its related iridoid compounds have been used in traditional herbal medicine for thε treatment of Jaundice hepatic diseases and various inflammatorys. For the purpose to increase trandsdermal absorption, the hydrolyzed products of Gardeniae Furctus were identified and assayed of active ingredients and investigated trandsdermal absorption and anti-inflammatory effects. Geniposide was hydrolyzed to genipin by ${\beta}-glucosidase$ and it was suggested that genipin was more suitable form than geniposide for transdermal absorption by its lipophilic property. Using Franz type diffusion cell and the skin of hairless mouse, the permeation rate of hydrolyzed products and their emulsion preparation were determined. Genipin have more increased absorption ratio through the skin of hairless mouse than geniposide. Also, the emulsion of hydrolyzed products of extracts showed higher permeability than that of nonhydrolyzed preparations. After 9 hours $280.85\;{\mu}g/cm^2$ of genipin was absorbed and $193.52\;{\mu}g/cm^2$ in case of geniposide. The Js of geniposide and genipin were $26.27{\pm}4.11\;{\mu}g/cm^2/hr$ and $40.35{\pm}5.04\;{\mu}g/cm^2/hr$ respectively. After carrageenan injection, the swelling was increased repidly to 24 hr and maintained as plateau. but emulsion group weer reached about 2.5 mL and the swelling decreased successively form 24 hr to 72 hr. The anti-inflammation effects of extracts and hydrolyzed products emulsion were increased with significant difference with control group after 24 hr, 48 hr and 72 hr. In carrageenan induced edema, inhibition of swelling was increased in case of hydrolyzed product emulsion compare with nonhydrolyzed group at 24 hr, 48 hr and 72 hr after swelling. In histological study, the anti-inflammatory effects of hydrolyzed products were remarkable at 48 hr and 72 hr compare with nonhydrolyzed. Hydrolyzed products of Gardeniae Fructus extracts containing genipin would be a suitable preparation to increase the transdermal absorption and anti-inflammatory effects.

• Journal of Pharmaceutical Investigation
• /
• 제34권2호
• /
• pp.131-138
• /
• 2004

This study was aimed to investigate the feasibility of nasal delivery of caffeine for the elimination of sleepiness. The effects of various vehicles, solubilizers, and enhancers on the permeation of caffeine through rabbit nasal mucosa was observed. The permeation study was carried out using a Franz-type permeation system at $37^{\circ}C$, and the amount of caffeine permeated though the rabbit nasal mucosa was determined by a validated HPLC. The apparent solubility and phys iochemical stability of caffeine in various nasal formulations were was determined. The effect of hydrotropes and modified cyclodextrins on the solubility of caffeine in water was determined by equilibrium solubility method. The solubility of caffeine in water was 29 mg/mL at $30^{\circ}C$. The addition of sodium benzoate and nicotinamide at 10% improved the solubility of caffeine (115 and 132 mg/mL, respectively) in aqueous solution. The flux of caffeine though the nasal mucosa from aqueous solution was $2.1{\pm}0.26\;mg/cm^2/hr$. The addition of sodium benzoate reduced its permeation $(1.4{\pm}0.01\;mg/cm^2/hr)$, but sodium benzoate with 5% $2HP{\beta}CD$ and 0.03% monoterpenes increased its permeation $(2.4{\pm}0.04\;mg/cm^2/hr)$ markedly. The addition of nicotinamide also increased also increased its permeation $(2.5{\pm}0.36\;mg/cm^2/hr)$. markedly. As the concentration of caffeine in nasal formulation increased, the permeation flux increased linearly. Caffeine was stable physicochemically and enzymatically in the nasal mucosa extract at $37^{\circ}C$. These results suggest that caffeine can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• 대한지역사회영양학회지
• /
• 제19권2호
• /
• pp.176-186
• /
• 2014

Objectives: Epidemiological studies have suggested that a higher consumption of whole grain foods can significantly reduce the risk of chronic diseases including cardiovascular diseases, type 2 diabetes and obesity. The objective of the current study was to examine associations among the consumption of whole grains and nutrient intakes and biochemical indicators associated with chronic diseases among generally healthy middle-aged Korean women. Methods: Using 24-hour recall data from the 2008-2009 National Health and Nutrition Examination Surveys, whole grain intake (g/day) was calculated for a total of generally healthy 1,953 subjects. The subjects were divided into three groups by the level of whole grain consumption (0 g/day, > 0 and < 20 g/day or ${\geq}20g/day$). Mean values or proportions of various nutrient intakes and metabolic risk factors were compared according to the level of whole grain consumption. All statistical analysis was conducted using SAS software version 9.2. Results: We observed that the overall consumption of whole grains was quite low. Specifically, 58.2% of subjects reported no whole grain consumption on the day of the survey, and the mean whole grain intake was only 15.3 g/day. The whole grain consumption was positively associated with intakes of various macro and micronutrients, namely, plant proteins and fats, dietary fiber, calcium, plant iron, potassium, zinc, vitamin A, ${\beta}$-carotene, thiamin, riboflavin, niacin, vitamin $B_6$ and folic acid. In addition, we found significantly decreasing trends in abdominal obesity and hypertriglyceridemia as whole grain intake levels increase. Conclusions: The study findings suggested the importance of promoting whole grain consumption as an efficient tool for improving various dietary aspects and preventing chronic diseases.

• Journal of Microbiology and Biotechnology
• /
• 제9권6호
• /
• pp.798-803
• /
• 1999

Prolyl endopeptidase [PEP; EC 3.4.21.26], a serine protease which is known to cleave peptide bonds on the carboxy side of a proline residue, plays an important role in the degradation of proline-containing neuropeptides that have been suggested to participate in learning and memory processes. An abnormal increase in the level of PEP, which can lead to generation of $A{\beta}$, is also suggested to be involved in Alzheimer's type senile dementia. In the course of screening PEP inhibitors from Basidiomycetes, the mushroom Polyozellus multiplex exhibited a high inhibitory activity against PEP. Two active compounds were isolated from the ethyl acetate soluble fraction by consecutive purification, using silica gel, Sephadex LH-20, and Lobar RP-18 chromatography. The chemical structures of these compounds were identified as thelephoric acid and 12-acety1-2,3,7,8-tetrahydroxy-[12H]-12-hydroxymethylbenzobis[I.2b,3.4b'] benzofuran-11-one (kynapcin-9) by spectral data including UV, IR, MS, HR-MS, $^1H-,{\;}^{13}C-$, and 2D-NMR. The $IC_{50}$ values of the thelephoric acid and kynapcin-9 were 0.157 ppm (446nM) and 0.087 ppm (212nM) and their inhibitor constants ($K_i$) were 0.73ppm ($2.09{\;}\mu\textrm{m}$) and 0.060 ppm (146 nM), respectively. Furthermore, they were non-competitive with a substrate in Dixon plots.

• Journal of Microbiology and Biotechnology
• /
• 제7권2호
• /
• pp.107-113
• /
• 1997

A strain producing a high amount of chitinase was isolated from soil, identified as Pseudomonas sp., and tentatively named Pseudomonas sp. YHS-A2. An extracellular chitinase of Pseudomonas sp. YHS-A2 was purified according to the procedure of ammonium sulfate saturation, affinity adsorption, Sephadex G-100 gel filtration and Phenyl-sepharose CL-4B hydrophobic interaction column chromatography. The molecular weight of the purified enzyme was estimated to be 55 kDa on SDS-PAGE was confirmed by active staining. Optimal pH and temperature of the enzyme are pH 7.0 and $50^{\circ}C$, respectively, and the enzyme is stable between pH 5.0 and 8.0 and below $50^{\circ}C$. The main products of colloidal chitin by the chitinase were N-acetyl-D-glucosamine and N,N'-diacetylchitobiose both of which were detected by HPLC analysis. The enzyme is supposed to be a random-type endochitinase which can degrade any position of ${\beta}$-l,4-linkages of chitin and chitooligosaccharides. The chitinase inhibited the growth of some phytopathogenic fungi, Fusarium oxysporum, Botrytis cineria, and Mucor rouxii and these antifungal effects were thought to be due to the characteristics of endochitinase.

• The Korean Journal of Physiology and Pharmacology
• /
• 제24권5호
• /
• pp.403-412
• /
• 2020

Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

• 응용통계연구
• /
• 제28권2호
• /
• pp.251-267
• /
• 2015

인도부페 프로세스는 유한개의 행과 무한개의 열로 이루어진 이진행렬의 분포와 관련된 확률과정이다. 무한특성모형을 유한개의 행과 무한개의 열로 이루어진 이진행렬을 이용해서 표현할 때, 이진행렬에 대한 사전분포로써 인도부페 프로세스가 이용될 수 있다. 본 논문에서는 인도부페 프로세스를 유한특성모형과 연관지어서 유도하는 방법을 소개하고, 베타프로세스와의 관련성을 간략히 설명한다. 실제 모형의 추론에 인도부페 프로세스가 이용되는 예제를 살펴보기 위해서 가우시안 선형모형에 인도부페 프로세스를 적용한 모형화 방법을 언급하고, 깁스표집 알고리즘, 막대 자르기 알고리즘, 변분방법을 이용한 추론방법을 설명한다. 그리고 이 세 가지 알고리즘을 이용하여 이미지 자료를 분석하는데 적용해본다. 나아가 쌍자료 분석, 네트워크 분석, 독립성분 분석에서 인도부페 프로세스가 어떻게 이용될 수 있는지도 알아본다.

• Archives of Plastic Surgery
• /
• 제34권2호
• /
• pp.156-162
• /
• 2007

Purpose: In the previous in vitro studies the bone marrow stromal cells(BSCs) have shown the superior effect for wound healing activity than fibroblasts, which includes cell proliferation, type I collagen synthesis, and the production of bFGF, VEGF and TGF-${\beta}$ in chronic wound healing. The aim of this study is to compare the effects of BSCs and fibroblasts on wound healing activity in vivo, especially on collagen synthesis. Methods: The fibroblasts and BSCs were harvested from patients and cultured. The cultured cells were infiltrated into the pores of polyethylene discs. These discs were divided into three groups according to the mixed cells. In groups I, II and III the discs were loaded with no cells, fibroblasts and BSCs, respectively. Twelve discs per group(total 36 discs) were made for this study. After creating 6 pockets in the back of each rats, each discs was implanted into each pockets. At three time intervals from 1 to 3 weeks, the implanted discs were harvested for the histological and quantitative analysis. The amount of collagen produced was evaluated using ELISA. Statistical comparisons were made using the Mann-Whitney U-test. Results: There was great difference in the collagen synthesis among the three groups by the 1st and 2nd weeks. The BSC group showed highest collagen level, followed by fibroblast group and no cell group(p<0.05). The 3rd week specimens also showed greater collagen amount in BSC and fibroblast groups compared to those of no cell group(p<0.05). However, there was little difference between BSC and fibroblast groups. Conclusion: This result demonstrates that BSC has superior effect on stimulating wound healing than fibroblast, which is currently used for wound healing.

• 동의생리병리학회지
• /
• 제20권4호
• /
• pp.853-860
• /
• 2006

This study was performed to investigate genes which are differently expressed in human blood by administrating of OLT-2. OLT-2 was medical precipitation composed of three medicinal herbs, Ginseng Radix, Astragali Radix, Glycyrrhizae Radix, and anti-leukemia effect of it was evaluated from Byung Hun Jeon of Wonkwang University this study was approved by Institutional Review Board of Korea Institute of Oriental Medicine (Taejeon, Korea) and four male subjects participated in this study. Gene expressions were evaluated by cDNA chip, in which 24,000 genes were spotted. Hierarchical cluster and biological process against the genes, which expression changes were more than 1.6 fold, were constructed by cluster 3.0 providing Stanford University and EASE(http://apps1 .maid.nih.gov/DAVID). Five groups were clustered according to their expression patterns. Group A contained gene decreased by OLT-2 and increased genes by OLT-2 were involved in Group B, C, D. In biological process, expression of genes involved in cytokine or cell calcium signaling, such as interleukin 18 and G-protein beta 4 were increased, but protein tyrosine phosphatase receptor type c, which function is cell adhesion between antigen-presenting cell and T or B-cell, was decreased by OLT-2. This study provides the most comprehensive available survey of gene expression changes in response to anti-leukemia effect of OLT-2 in human blood.