• Title/Summary/Keyword: First-in-human dose

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Micronutrients as Supportive Care for Gastrointestinal Cancer Patients; Benefits and Concerns

  • Yoo-Sun Kim;Yuri Kim
    • Journal of Digestive Cancer Research
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    • v.1 no.2
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    • pp.82-88
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    • 2013
  • Cancer is the first leading cause of death in Korea and the second leading cause of death in the USA. There is extensive research into prevention of cancer and the support of oncology patients with diet or dietary supplements. In vitro and in vivo animal studies have indicated that antioxidants, including beta-carotene, alpha-tocopherol, and ascorbic acid, can yield anti-cancer effects in addition to providing protection against oxidative damage. Although many observational studies have shown that consuming fruits and vegetables can reduce the risk of some cancers, the results of several large-scale human intervention trials testing the benefits of a single or combined higher-dose of individual micronutrients have been inconsistent. Cancer can cause profound metabolic and physiological changes which may affect patients' nutrient requirements. Although the optimal route of nutrient delivery is through diet, cancer patients often suffer symptoms that disrupt their food intake, including anorexia, premature satiety, altered taste and smell, and changes in bowel mobility. In particular, micronutrient deficits can slow postoperative healing, contribute to depression symptoms, and decrease immune competence. Cancer patients are generally motivated to take dietary supplements to improve responses to treatment and quality of life. The Physician's Health Study II (PHS II) randomized controlled trial reported recently that daily multivitamin supplementation significantly, albeit modestly, reduced the risk of total cancer. Although evidence of multivitamin use benefits is limited in cancer patients, taking dietary supplements with constituents in the range of the recommended daily allowance according to the Dietary Reference Intake (DRI) recommendation is generally considered to be safe.

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Long-Term Administration of Sopungsungi-won (SP) Prevents Diabetic Nephropathy in Zucker Diabetic Fatty Rats

  • Kim, Youn-Young;Kang, Kwi-Man;Chung, Sung-Hyun
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.917-922
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    • 2002
  • We investigated the long term effects of Sopungsungi-won (SP), a Korean traditional formula used for senile constipation and diabetes mellitus, on the development of diabetic nephropathy (DN) in Zucker diabetic fatty (ZDF) rats. ZDF rats were fed regular laboratory chow mixed with SP or rosiglitazone (RSG) for an 8-week period. Kidney hypertrophy was developed with increasing plasma glucose level, and glomerular hypertrophy was improved by 22% and 45% in SP- and RSG-treated rats, respectively. Urinary glucose and albumin excretions were also significantly lower in SP-treated rats than in ZDF control rats. Activation of the mitogen-activated protein kinase (MAPK)-transforming growth factor ${\beta}1$ (TGF ${\beta}1$)-fibronectin pathway in kidney, responsible for glomerular dysfunction, was markedly blunted by SP treatment in a dose dependent manner. Our findings, for the first time, provide strong evidence that long-term administration of SP formula prevents the development and progression of DN in ZDF rats. Human trials are needed to confirm these experimental results.

Several Human Pharmaceutical Residues in Aquatic Environment may Result in Endocrine Disruption in Japanese Medaka(Oryzias latipes)

  • Kang, Hee-Joo;Kim, Hyun-Soo;Choi, Kyung-Ho;Kim, Kyung-Tae;Kim, Pan-Gyi
    • Journal of Environmental Health Sciences
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    • v.31 no.3
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    • pp.227-233
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    • 2005
  • This study was conducted to determine the endorcrine disruption effects of the several major pharmaceutical residues in water using adult Japanese medaka (Oryzias latipes). Four frequently used pharmaceuticals including caffeine, ketoconazole, acetaminophen, and diltiazem were investigated for the vitellogenin(Vtg) induction in the medaka using Western blotting and ELISA. $17\beta$,-estradiol was used as a positive control. Vtg was qualified and quantified through Western blot and ELISA. Following SDS gel electrophoresis, the dominant protein band was identified to molecular weight approximately 205 kDa in whole body samples of vitellogenic female. With female medaka exposed to $17\beta,-estradiol$, no significant difference in total protein induction was noted. In contrast, three to five day exposure of male fish to $17\beta,-estradiol$ resulted in $63.07\%o$, increase of total protein comparing to that of control males (p<0.01). Vtg induction in male fish was observed with all the test pharmaceuticals: At concentrations greater than 1ppm of diltiazem, 2 ppm of caffeine, 4 ppm of acetaminophen, and 10 ppm of ketoconazole, Vtg induction was monotonously increased in a dose dependent manner. This study is one of the first reports suggesting potential endocrine disruption mechanism of common human pharmaceutical products in aquatic ecosystem. Although the effect concentrations obtained from this investigation are environmentally unrealistically high, endocrine disruption should be considered as one of the important consequences of pharmaceutical pollution in aquatic environment, and warrants due attention in future researches.

Echinostoma aegyptica (Trematoda: Echinostomatidae) Infection in Five Riparian People in Savannakhet Province, Lao PDR

  • Chai, Jong-Yil;Jung, Bong-Kwang;Chang, Taehee;Shin, Hyejoo;Sohn, Woon-Mok;Eom, Keeseon S.;Yong, Tai-Soon;Min, Duk-Young;Phammasack, Bounlay;Insisiengmay, Bounnaloth;Rim, Han-Jong
    • Parasites, Hosts and Diseases
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    • v.58 no.1
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    • pp.67-72
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    • 2020
  • Human infection with Echinostoma aegyptica Khalil and Abaza, 1924 (Trematoda: Echinostomatidae) is extremely rare. In this study, we confirmed E. aegyptica infection in 5 riparian residents living along the Mekong River in Savannakhet Province, Lao PDR. The patients revealed eggs of Opisthorchis viverrini/minute intestinal flukes, echinostomes, and other parasites in fecal examinations using the Kato-Katz technique. Following treatment with praziquantel 30-40 mg/kg and pyrantel pamoate 10-15 mg/kg in a single dose and purging with magnesium salts, adult specimens of various helminth species were collected. Among the trematodes, echinostome flukes of 4.5-7.6 mm in length (n = 134; av. 22.3 specimens per case) were of taxonomic interest and subjected in this study. The flukes were morphologically characterized by having total 43-45 collar spines arranged in 2 alternating rows (corner spines usually 5 on each side) and compatible with previous descriptions of E. aegyptica. The patients were mixed-infected with other helminths, so specific clinical manifestations due to this echinostome fluke were difficult to determine. The present paper describes for the first time human E. aegyptica infections in Lao PDR. This is the second report of human infection (2nd-6th cases) with E. aegyptica in the world following the first one from China.

Inhibitory Effects of Gaejibokryunghwan on Cell Proliferation in HeLa Cells (계지복령환(桂枝茯笭丸)의 HeLa Cell 증식억제(增殖抑制)와 사멸효과(死滅效果))

  • Hwang Deok-Sang;Cho Jung-Hoon;Jang Jun-Bock;Lee Kyung-Sub
    • The Journal of Korean Medicine
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    • v.27 no.1 s.65
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    • pp.23-35
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    • 2006
  • Objectives : This study was conducted to investigate the inhibitory effects of Gaejibokryunghwan on cell proliferation in HeLa cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Gaejibokryunghwan extract solution. All three were cultured for 24 hours, 48 hours and 72 hours each, to examine the inhibitory effects of Gaejibokryunghwan. Afterwards, we drew out the effect of Gaejibokryunghwan extract solution by making 5 analysis. First analysis was to measure the proliferation rate of cells. Second was FACS analysis. Third was to estimate the activity or caspase-3. Fourth, we used XTT assay to analyze the activation or cells. Ana lastly, a molecular biological method was used to determine activation of MAP kinase in the HeLa cells. Results : After 24, 48 and 72 hours cultivation, the proliferation of HeLa cells showed the dose-dependent decrease in all Gaejibokryunghwan extract solution groups compared to the control group. In the FACS analysis, Gaejibokryunghwan extract solution groups showed increased caspase expression compared to the control group, except for the group for 48 and 72 hours in 1 % concentrate. Caspase-3 activities were increased in all, except tile group cultured for 24 hours in 5% concentrate and the groups cultured for 48 hours in 1% and 5% concentrate. In the XTT study, 1% Gaejibokryunghwan extract solution groups showed increase compared to the control group, but other Gaejibokryunghwan extract solution containing groups showed significant decrease compared to the control after 24, 48 and 72 hours of cultivation. The expressions of MAP kinase were decreased in all Gaejibokryunghwan extract solution containing groups compared to the control group after 24, 48 and 72 hours of cultivation. Conclusions : From this study, we could suggest that Gaejibokryunghwan be available to the inhibition of proliferation of human cervical carcinoma cell line, HeLa cells in vitro.

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The Influence of DHA Supplementation in Maternal Diets on Fatty Acid Compositions of Plasma Lipids and Human Milk (수유기에 식이와 함께 섭취한 DHA가 산모의 혈액과 모유의 지질조성에 미치는 영향)

  • 조여원
    • Journal of Nutrition and Health
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    • v.29 no.2
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    • pp.213-222
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    • 1996
  • The most abundant long-chain polyunsaturated fatty acid in brain lipids is docosahexaenoic acid(C22 : 6 N-3, DHA). It is incorporated into nerve tissues mostly in utero and during the first year of life. DHA in brain is derived from either pre-formed DHA in human milk or by infant hepatic synthesis from linolenic acid in milk. This study was designed to investigate the effects of DHA supplementation on fatty acid profiles in maternal plasma lipid and breast milk. Twenty lactating women participated in the study. Seven women took 3g of fish oil per day and vitamin E for 28 days starting from the day of giving birth. Five women consumed 1.5g of fish oil as well as tivamin E, and the rest took vitamin E supplements for the same period of time. Dietary questionnaires and 3 consecutive 24-h recalls were collected to evaluate theri nutritional status and food habits. Finding that DHA intake from fish was not significantly different among three experimental groups, the partcipants were instructed to continue eating their usual home diets. Milk samples were taken on the day of giving birth, as well as the 7th, 14th and 28th day being the supplement phase, and finally 2 weeks after the cessating of DHA supplements. The amounts of the fish oil supplements produced significant dose-dependent increased in the DHA content of milk and plasma, but to a lesser degree. Base-line for 28 days raised the level to 2.05$\pm$0.43% and 1.5g/day supplement produced DHA levels of 1.02$\pm$0.19%. The results of this study indicated that relatively small amount of dietary DHA supplementation significantly elevats DHA content in milk. This would clearly elevate the infant's DHA intake which in turn may have implications for the infant's brain development.

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Echinochasmus caninus n. comb. (Trematoda: Echinostomatidae) Infection in Eleven Riparian People in Khammouane Province, Lao PDR

  • Chai, Jong-Yil;Chang, Taehee;Jung, Bong-Kwang;Shin, Hyejoo;Sohn, Woon-Mok;Eom, Keeseon S.;Yong, Tai-Soon;Min, Duk-Young;Phammasack, Bounlay;Insisiengmay, Bounnaloth;Rim, Han-Jong
    • Parasites, Hosts and Diseases
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    • v.57 no.4
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    • pp.451-456
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    • 2019
  • Adult specimens of Echinochasmus caninus n. comb. (Verma, 1935) (Trematoda: Echinostomatidae) (syn. Episthmium caninum Yamaguti, 1958) were recovered from 11 riparian people who resided along the Mekong River in Khammouane Province, Lao PDR. In fecal examinations done by the Kato-Katz technique, the cases revealed eggs of Opisthorchis viverrini/minute intestinal flukes, hookworms, and in 2 cases echinostome eggs. To recover the adult helminths, praziquantel 30-40 mg/kg and pyrantel pamoate 10-15 mg/kg in a single dose were given and purged with magnesium salts. Various species of trematodes (including O. viverrini and Haplorchis spp.), cestodes, and nematodes were recovered from their diarrheic stools. Among the trematodes, small echinostome flukes (n=42; av. 3.8 specimens per case) of 0.7-1.2 mm in length are subjected in this study. They are morphologically characterized by having 24 collar spines interrupted dorsally and anterior extension of vitellaria from the cirrus sac or genital pore level to the posterior end of the body. Particularly based on this extensive distribution of vitellaria, the specific diagnosis was made as Echinochasmus caninus. The cases were co-infected with various other helminth parasites; thus, clinical manifestations specific for this echinostome infection were difficult to determine. The present paper describes for the first time human E. caninus infections in Lao PDR. Our cases marked the 4-14th human infections with this echinostome around the world following the 3 previous cases reported from Thailand.

Ethacrynic Acid and Citral Suppressed the All Trans Retinoid-Induced Monocyte Chemoattractant Protein-1 Production in Human Dermal Fibroblasts

  • Kim, Kwang-Mi;Noh, Min-Soo;Kim, Soo-Hyun;Park, Mi-Kyung;Lee, Hye-Ja;Kim, Soo-Youl;Lee, Chang-Hoon
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.71-76
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    • 2010
  • Skin irritation caused by retinol and retinoic acid results in mild erythema called as retinoid dermatitis. To develop compounds modulating the retinoid dermatitis, we tried to establish the screening method for retinoid dermatitis. At first we examined the inflammatory cytokine profile in neonatal human dermal fibroblasts which are known to be one of main site of retinoid action. As a result, interleukin-8 (IL-8) and monocytes chemoattractant protein-1 (MCP-1) were significantly produced by all trans retinoic acid (ATRA) and all trans retinol (ATROL) in dermal fibroblasts. Especially the production of MCP-1 was more than that of IL-8. The production of MCP-1 by retinoid was dose-dependently increased, continuing up to 24 hrs. After then using ethacrynic acid (ECA) known to reduce mouse ear edema induced by ATRA, we checked whether ECA suppressed the production of MCP-1. As a result, ECA effectively suppressed the production of MCP-1 in the ATRA- or ATROL-treated-fibroblasts. These results suggested that screening method effectively reflects the in vivo anti-inflammatory activity of ECA. It was reported that citral inhibited the enzyme involved in the conversion of ATROL to ATRA. We showed that citral suppressed the production of MCP-1 in ATROL-treated fibroblasts. We expect these finding might be helpful to find useful compounds modulating the side effects of retinoid or retinoid dermatitis.

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

  • Sung, Ho-Joong;Son, Sin-Jee;Yang, Seung-Ju;Rhee, Ki-Jong;Kim, Yoon-Suk
    • BMB Reports
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    • v.45 no.7
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    • pp.414-418
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    • 2012
  • Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-$1{\beta}$ (IL-$1{\beta}$) mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TG-induced downregulation of IL-$1{\beta}$, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-$1{\beta}$, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-$1{\beta}$ expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-$1{\beta}$ expression by TG-treated macrophages may play a role during atherogenesis.

Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet

  • Min, Byulchorong;Lee, Heejin;Song, Ji Hye;Han, Myung Joo;Chung, Jayong
    • Nutrition Research and Practice
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    • v.8 no.6
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    • pp.655-661
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    • 2014
  • BACKGROUND/OBJECTIVES: The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on adiposity were examined. MATERIALS/METHODS: 3T3-L1 cells were treated with arctiin (12.5 to $100{\mu}M$) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks. RESULTS: Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key adipogenic regulators $PPAR{\gamma}$ and $C/EBP{\alpha}$, and also significantly inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue. CONCLUSIONS: Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of $PPAR{\gamma}$ and $C/EBP{\alpha}$ and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.