Thioredoxin reductase (TrxR) is one class of the most important antioxidant selenoproteins and is involved in regulating tumor genesis and progression. It has been reported that naphthoquinones can target and inhibit TrxR1 activity therefore produce reactive oxygen species (ROS) mediated by TrxR1, resulting into cellular redox imbalance and making the naphthoquinone compounds to become potential antitumor chemotherapy drugs. The purpose of this work is to explore the interaction between TrxR1 and menadione using biochemical and mass-spectrometric (MS) analyses, to further reveal the detailed mechanisms of TrxR1-mediated naphthoquinone reduction and inhibition of TrxR1 by naphthoquinone compounds. Using the site-directed mutagenesis and recombinantly expressed TrxR1 variants, we measured the steady-state kinetic parameters of menadione reduction mediated by TrxR1 and its variants, performed the inhibition analysis of menadione on TrxR1 activity, and eventually identified the interaction between menadione and TrxR1 through MS analysis. We found that Sec-to-Cys mutation at residue of 498 significantly enhanced the efficiency of TrxR1-mediated menadione reduction, though the Sec⁴⁹⁸ is capable to catalyze the menadione reduction, indicating that TrxR1-mediated menadione reduction is dominantly in a Se-independent manner. Mutation experiments showed that Cys⁴⁹⁸ is mainly responsible for menadione catalysis in comparison to Cys⁴⁹⁷, while the N-terminal Cys⁶⁴ is slightly stronger than Cys⁵⁹ regarding the menadione reduction. LC-MS results detected that TrxR1 was arylated with one molecule of menadione, suggesting that menadione irreversibly modified the hyper-reactive Sec residue at the C-terminus of selenoprotein TrxR1. This study revealed that TrxR1 catalyzes the reduction of menadione in a Se-independent manner meanwhile its activity is irreversibly inhibited by menadione. Hereby it will be useful for the research and development of naphthoquinone anticancer drugs targeting TrxR1.
Catalysis ; Drug Development ; Oxidation-Reduction ; Thioredoxin Reductase 1/metabolism* ; Vitamin K 3/metabolism*

BACKGROUND: Cases of dermatitis induced by the injection of certain drugs have been reported. OBJECTIVE: The aim of this study was to assess the cause and clinicopathologic findings of injection-induced dermatitis, and to reveal whether the reaction has any relation to the patient's age, injection site, drug concentration, and time interval from the injection to the occurrence of the skin lesion. METHODS: In this study, we enrolled 10 patients who developed erythematous skin lesions after the injection of causative drugs. The lesions were compared to each other according to the injection site, time interval from the injection to the occurrence of the skin lesion, and clinical characteristics. We performed intradermal and patch tests in each patient with different concentrations of causative drugs. RESULTS: The most common causative drugs were diclofenac and vitamin K1. The eczematous type was the most frequent clinical type. The intradermal test showed more positive results than the patch test. The patch tests with diclofenac (as is, 2.5%, 5%, and 10%) and vitamin K1 (10%) were all negative in 10 patients. Furthermore, intradermal tests with diclofenac (as is) and vitamin K1 (0.1%, 1%, and 10%) were performed in 8 patients. Six patients had a positive reaction, consisting of erythema, induration, and vesiculation, after 1 and 2 days. CONCLUSION: Our results showed that the most common causative agents were diclofenac and vitamin K1. Moreover, it seems that that intradermal test is more useful than the patch test in the diagnosis of injection-induced dermatitis.
Dermatitis* ; Diagnosis ; Diclofenac ; Erythema ; Humans ; Intradermal Tests ; Patch Tests ; Skin ; Vitamin K ; Vitamin K 1

Vitamin K is a lipid-soluble vitamin used in the treatment of hypoprothrombinemia found in diseases of the liver, biliary tract and small intestine. Vitamin K1 (Phytonadione) is the natural form of vitamin K. Recently, a cream containing vitamin K1 has been marketed for topical use in the treatment of periorbital hyperpigmentation, telangiectasia and rosacea. Vitamin K1 dermatitis is a cutaneous adverse reaction to vitamin K1 and can cause acute pruritic, erythematous, eczematoid, indulated plaques or slowly-appearing sclerodermatous plaques. We present a case of dermatitis caused by a vitamin K1 intralesional injection for treatment of facial telangiectasia and flushing.
Biliary Tract ; Dermatitis* ; Flushing ; Hyperpigmentation ; Hypoprothrombinemias ; Injections, Intralesional* ; Intestine, Small ; Liver ; Rosacea ; Telangiectasis ; Vitamin K ; Vitamin K 1* ; Vitamins*

BACKGROUND/OBJECTIVES: Rheumatoid arthritis (RA) is associated with an excess mortality from cardiovascular disease which is likely attributed to an atherogenic lipid profile. Among nutritional factors vitamin K has been recently focused as a pivotal nutrient in improvement of lipid related markers. Thus, this study was designed to determine the effects of vitamin K on lipid profile in this disease. SUBJECTS/METHODS: Fifty eight patients with definitive RA were participated in the present double blind placebo controlled study. They were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] (n = 30) or placebo pills (n = 28), for eight weeks. In order to control the effects of probable confounders dietary intakes, anthropometric measurements including weight and height, clinical status using disease activity score-28 (DAS-28), physical activity and anxiety status were evaluated at baseline. Moreover, serum levels of lipid related markers including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were measured at baseline and at the end of intervention. RESULTS: There were no significant differences between the two groups regarding any of the baseline characteristics. After adjusting for some relevant confounders, in comparison between two groups, we observed no significant changes in lipid related markers at the end of intervention. Also, there was no significant difference between before and after intervention values within groups (P > 0.05). CONCLUSIONS: Function of vitamin K1 in lipid profile modification remains still controversial. This study showed that vitamin K1 has no effect on lipid profile in women with rheumatoid arthritis. Further studies with a longer follow-up are required to determine the effects of vitamin K on atherogenic lipid profile.
Anxiety ; Arthritis, Rheumatoid* ; Cardiovascular Diseases ; Cholesterol ; Female ; Humans ; Lipoproteins ; Mortality ; Motor Activity ; Triglycerides ; Vitamin K ; Vitamin K 1*

BACKGROUND/OBJECTIVES: Rheumatoid arthritis (RA) is associated with an excess mortality from cardiovascular disease which is likely attributed to an atherogenic lipid profile. Among nutritional factors vitamin K has been recently focused as a pivotal nutrient in improvement of lipid related markers. Thus, this study was designed to determine the effects of vitamin K on lipid profile in this disease. SUBJECTS/METHODS: Fifty eight patients with definitive RA were participated in the present double blind placebo controlled study. They were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] (n = 30) or placebo pills (n = 28), for eight weeks. In order to control the effects of probable confounders dietary intakes, anthropometric measurements including weight and height, clinical status using disease activity score-28 (DAS-28), physical activity and anxiety status were evaluated at baseline. Moreover, serum levels of lipid related markers including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were measured at baseline and at the end of intervention. RESULTS: There were no significant differences between the two groups regarding any of the baseline characteristics. After adjusting for some relevant confounders, in comparison between two groups, we observed no significant changes in lipid related markers at the end of intervention. Also, there was no significant difference between before and after intervention values within groups (P > 0.05). CONCLUSIONS: Function of vitamin K1 in lipid profile modification remains still controversial. This study showed that vitamin K1 has no effect on lipid profile in women with rheumatoid arthritis. Further studies with a longer follow-up are required to determine the effects of vitamin K on atherogenic lipid profile.
Anxiety ; Arthritis, Rheumatoid* ; Cardiovascular Diseases ; Cholesterol ; Female ; Humans ; Lipoproteins ; Mortality ; Motor Activity ; Triglycerides ; Vitamin K ; Vitamin K 1*

Activity-guided separation of the methylene chloride-soluble fraction of the leaves of Zanthoxylum schinifolium, resulted in the isolation of four coumarinoids (1 - 4), two triterpenoids (5, 6) and three fatty acid derivatives (7 - 9) as active principles. Their chemical structures were identified as collinin (1), 8-methoxyanisocoumarin (2), 7-(6'R-hydroxy-3',7'-dimethylocta-2',7'-dienyloxy)-coumarin (3), (E)-4-methly-6-(coumarin-7'-yloxy) hex-4-enal (4), lupeol (5), epi-lupeol (6), phytol (7), hexadec-3-enoic acid (8) and palmitic acid (9), on the basis of spectroscopic (1D, 2D and MS) data analyses and comparing with the data published in the literatures. Compounds 1 and 7 showed potent cytotoxicity against Jurkat T cells with IC50 values of 45.58 and 47.51 microM, respectively. The others showed moderate activity with IC50 values ranging around 80.58 to 85.83 microM, while the positive control, auraptene, possessed an IC50 value of 55.36 microM.
Inhibitory Concentration 50 ; Palmitic Acid ; Phytol ; Rutaceae ; Statistics as Topic ; T-Lymphocytes ; Zanthoxylum*

PURPOSE: Vitamin K deficiency is associated with hemorrhagic disease of the newborn. Late hemorrhagic disease is often intracranial and may be fatal. Many countries recommend vitamin K prophylaxis after birth to prevent this hazard of vitamin K deficiency. Nevertheless, there are still controversies concerning the best way of providing effective prophylaxis. A recent article by Golding and colleagues has questioned the safety of the routine use of intramuscular vitamin K for the newborn. These authors reported a significantly increased rate of childhood cancer in infants who received intramuscular prophylaxis. So we compared the prophylactic effect of intramuscular, oral, and maternal administration of vitamin K on hemorrhagic disease of the newborn. METHODS: A total of 60 newborns, delivered spontaneously vaginally, in the Masan Fatima hospital from March to June, 1996, were enrolled. Neonated with intrapartum anoxia, liver disease or hereditary coagulation factor deficiencies, who received antibiotics were excluded. Mothers receiving any medication known to interferes with vitamin K metabolism(such as antiepileptics, antibiotics and anticonvulsions) were excluded. The newborns were randomly allocated to one of the four groups. A group was not supplied. B group received 1mg of vitamin K1 intramusculary, C group received 2mg of vitamin K1 orally. D group was given 20mg of vitamin K1 orally to their mothers at least 2days(range 2 to 7) before birth. Blood samples were collected from 48hrs to 72hrs after birth. PIVKA-II level was measured by enzyme-linked immunosorbent assay (EITEST-MONOP, Eisai Ltd), using a monospecific monoclonal antibody against PIVKA-II. The results obtained are expressed in arbitrary unit (AU) : 1AU corresponds to 1micro gram of purified prothrombin. (healthy adults have less than 0.13AU/ml). PT, PTT were measured simultaneously. RESULTS: 1) PIVKA-II was detected in 4 of 15 infants in group A, who were not supplied. None was detected in other groups. So PIVKA-II detection rate was significantly decreased in other groups compared with group A(p<0.05). 2) PT(sec) values were 12.74+/-0.91, 12.58+/-0.89, 12.36+/-1.04, 12.16+/-0.90 respectively, and there was no significant difference between groups. 3) PTT(sec) values were 52.41+/-13.26, 38.39+/-10.04, 42.67+/-7.01, 39.77+/-10.48 respectively and there was significant shortening in other groups compared with group A (p<0.05). CONCLUSION: Not only intramuscular administration but oral and maternal administration of vitamin K have prophylactic effect on hemorrhagic disease of the newborn. Prophylactic effect on the late hemorragic disease of the newborn requires further extensive study and evaluation.
Adult ; Anoxia ; Anti-Bacterial Agents ; Anticonvulsants ; Blood Coagulation Factors ; Enzyme-Linked Immunosorbent Assay ; Humans ; Infant ; Infant, Newborn* ; Liver Diseases ; Mothers ; Parturition ; Prothrombin ; Vitamin K 1 ; Vitamin K Deficiency ; Vitamin K* ; Vitamins*

BACKGROUND: Two types of local reactions due to cutaneous administration of vitamin K. eczematoid, and indurated pilaque and localized scleroderma, have been described. In the acute phase, a generalized maculopapular eruption (Id reation) may accompany either reaction. Liver disease has been reported with vitamir K hypersensitivity but the mechanism of vitamin K dermatitis is unknown. OBJECTIVE & MEHTODS: In 10 of vitamin K dermatitis patients, we studied the clinical features, histopathologic findings, and provocation tests (patch test & intrader nal test). RESULTS: 1. All patients had localized erythematous plaque but none had sclerodermoid skin eruption. Four patients were associated with Id reaction. 2. The onsets of eruptions after initial injection of vitamin K were within one week (one case), 2 to 3weeks(seven cases), or 3 weeks (two cases), and the doses of administered vitamin K were between 30 and 310 mg. 3. Four had liver diseases and 5 had blood eosinophilia. 4. Of 7 patients who had patch-and intradermal test, intradermal test showed all positive at either day 2 or day 4 but patch test were all negative. 5. The histopathologic findings of all the cases showed perivascuiiar and diffuse infiltrations of numeroas osinophils and mononuclear cells and one case showed panniulitis. CONCLUSION: The cell-mediated immune reaction may play a role on the pathogenesis of vitamin K, dermatitis. Liver dysfuncticn and/or another factors may be a precivitating factor of vitamin K dermatitis, and intradermal the seems to be more useful in the diagnoiis of vitamin K dermatitis than patch test.
Administration, Cutaneous ; Dermatitis* ; Eosinophilia ; Humans ; Hypersensitivity ; Intradermal Tests ; Liver ; Liver Diseases ; Patch Tests ; Scleroderma, Localized ; Skin ; Vitamin K ; Vitamin K 1* ; Vitamins*

There is little information on dietary vitamin K intake and nutritional status of daily requirements of vitamin K in Korea. The objective of this study was to investigate the vitamin K intake and major food sources of Vitamin K in Koreans. The survey data from the 2010-2011 Korean National Health and Nutrition Examination Survey of 7,792 subjects (aged 19-64 years) were examined. Total vitamin K intake was calculated from 24-hour dietary recall using a vitamin K food database, Computer Aided Nutritional analysis Program and the United States Department of Agriculture database. The geometric mean of vitamin K was estimated as 322.40 +/- 6.33 ug/day for men and 271.20 +/- 4.92 ug/day for women. Daily vitamin K intake increased significantly with age (p for trend < 0.001). The main food source of vitamin K was vegetables (72.84%), including cabbage kimchi (19.26%), spinach (17.38%), sesame leaves (7.11%), radish leaves (6.65%), spring onions (6.28%), and laver (4.82%), followed by seaweed, seasonings, and fat and oils. We observed that the vitamin K intake of Koreans was relatively higher than that reported by other studies in Western countries and differed depending on age.
Brassica ; Female ; Humans ; Korea ; Male ; Nutrition Surveys* ; Nutritional Status ; Oils ; Onions ; Raphanus ; Seasons ; Seaweed ; Sesamum ; Spinacia oleracea ; United States Department of Agriculture ; Vegetables ; Vitamin K 1 ; Vitamin K* ; Vitamins*

The prevalence of chronic diseases have been rising in the developing countries because of their increased animal foods consumption and Western lifestyle. Lately, vegetarian diet that exclude animal products get public attention. The purpose of this study was to evaluate the nutritional status and dietary quality of vegetarians, and their consumption of vitamin K and was also assessed. Vegetarians including strict vegan and lacto-ovo-vegetarian consumed their diet at least over 6 months. Carnivores were gender and age matched with vegetarians and they consumed over 50% of protein and fat from animal sources. Current nutrient intakes and dietary quality were assessed using 3-day food records and intake of vitamin K was calculated from the data base of "Provisional Table on the vitamin K contents of foods, USA". Blood sample were collected and biochemical parameters and plasma phylloquinone concentrations were analyzed. Anthropometric data from vegetarian and carnivore were not significantly different. The intake of calories, protein, vitamin B2, Ca and Zn of the vegetarians were remarkably lower than RDA for each nutrient. Moreover, index of nutritional quality and nutrient adequacy ratio of vegetarians were lower than those of carnivore. Vegetarian consumed less fat and the ratio of n-6/n-3 fatty acid was lower in vegetarian. The intake of essential amino acids in vegetarian was significantly lower than that of carnivore. The vitamin K consumption and plasma phylloquinone concentration of vegetarian were significantly higher than those of carnivore (p < 0.05). The dietary vitamin K consumption was positively correlated with plasma phylloquinone levels in vegetarian (p < 0.01).
Amino Acids, Essential ; Animals ; Chronic Disease ; Developing Countries ; Diet ; Diet, Vegetarian ; Life Style ; Nutritional Status ; Nutritive Value ; Plasma ; Prevalence ; Riboflavin ; Vitamin K 1 ; Vitamin K* ; Vitamins*