Bromadiolone, commonly known as super warfarin, is a long-acting coumarin dicoumarin rodenticide. The mechanism of bromadiolone is mainly to inhibit vitamin K1 epoxide reductase and affect the synthesis of coagulation factors Ⅱ, Ⅶ, Ⅸ and Ⅹ, which causes blood coagulation dysfunction and systemic multiple organ hemorrhage. Here, we report of a case of bromadiolone poisoning patient who had digestive tract, abdominal hemorrhage, as well as secondary paralytic ileus. After blood product transfusion and vitamin K1 supplementation, the patient was discharged after the physical condition was improved. It's suggestied that clinicians should pay attention to rare complications to prevent missed diagnosis when treating other bromadiolone poisoning.
4-Hydroxycoumarins ; Blood Coagulation Factors ; Dicumarol ; Hemorrhage ; Humans ; Intestinal Pseudo-Obstruction/chemically induced* ; Oxidoreductases ; Rodenticides ; Vitamin K 1 ; Warfarin

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*

OBJECTIVE: Growth-arrest-specific protein 6 (Gas6) is a vitamin K-dependent protein and involved in cell proliferation, survival, adhesion and migration . Also it has been shown to play an important role in the inflammatory response .The aim of present study was to investigate the role of Gas6 in the process of the expression of adhesion molecules and chemokines of human umbilical vein endothelial cells (HUVECs) induced by Porphyromonas gingivalis lipopolysaccharide(P.g-LPS). METHODS: After up-regulation and down-regulation of the expression of Gas6, the vascular endothelial cells were stimulated with 1 mg/L P.g-LPS for 3 h and 24 h. Real-time quantitative polymerase chain reaction(real-time PCR) was taken to detect the expression of the cell adhesion molecules:intercellular adhesion molecule-1 (ICAM-1) and E-selectin, as well as chemokines:interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1). Wound healing assay was taken to observe the migration ability of endothelium cells in different groups. RESULTS: After 3 h of P.g-LPS stimulation, the expression of adhesion molecules and chemokine in the down-regulation group was not significantly different from that in the control group,while in the up-regulation group the decrease of E-selectin, ICAM-1, IL-8 and MCP-1 was 81%±0%, 47%±3%, 76% ± 3%, 26% ± 6% respectively. After 24 h of P.g-LPS stimulation, the expression of adhesion molecules and chemokine in down-regulation group was significantly higher than that in control group (2.06±0.07, 1.99±0.11, 3.14±0.15, 1.84±0.03 flod), while these molecules in the down-regulation group was significantly lower than in the control group (29%±1%, 62%±3%, 69%±1%, 41%±2%). Differences were statistically significant (P<0.01). Wounding healing assay showed that down-regulation of Gas6 enhanced migration ability of endothelial cells while up-regulation of Gas6 weakened this ability,which was consistent with the trend of real-time PCR result. CONCLUSION Down-regulation of the Gas6 gene enhanced the expression of ICAM-1, E-selectin, IL-8 and MCP-1 in HUVECs after P.g- LPS stimulating, while up-regulaiton of the Gas6 gene weakened the expression of ICAM-1, E-selectin, IL-8 and MCP-1 in HUVECs after P.g-LPS stimulating,suggesting that Gas6 may play a role in the process of endothelial cell adhesion.
Cell Adhesion ; Cell Adhesion Molecule-1 ; Cells, Cultured ; Chemokines/metabolism* ; E-Selectin/metabolism* ; Endothelium, Vascular ; Humans ; Intercellular Signaling Peptides and Proteins/physiology* ; Lipopolysaccharides ; Porphyromonas gingivalis/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Vitamin K

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

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*

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*

Vitamin K1 dermatitis is a cutaneous adverse reaction to vitamin K1, and this malady presents as an erythematous eczematoid patch or pseudoscleroderma. At first, liver disease was thought to be related to vitamin K1 dermatitis. However, it is no longer considered as being related to liver disease due to the increasing case reports of patients with vitamin K1 dermatitis and who are without liver disease. Type IV hypersensitivity reaction was suspected to be the cause of this reaction. This disease can be easily ignored because of its low incidence. We hereby report on a case of vitamin K1 dermatitis that was confirmed by a skin test.
Dermatitis ; Humans ; Hypersensitivity, Delayed ; Incidence ; Liver Diseases ; Skin Tests ; Vitamin K 1 ; Vitamins

OBJECTIVETo summarize the clinical characteristics of secondary coagulation disorders caused by exposure to poison (raticide) in children and to investigate the diagnosis and corresponding treatment.

METHODThe process of diagnosis, clinical characteristics, response to treatment and the prognosis were analyzed.

RESULTSThe main clinical manifestation was mucosal bleeding (66.6%), including epistaxis, gingival bleeding, hematomas and so on. All these children were previously well and had no history of bleeding. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged, factor II was undetectable and the levels of factors VII, IX, and X were lower. The fibrinogen was normal. A raticide was detected in blood and urine of 13 children although 12 of the patients had no definite history of raticide ingestion. Prothrombin complex, fresh frozen plasma and vitamin K(1) were effective in these cases. However, 2 - 3 weeks later, 6 patients presented with recurrent bleeding.

CONCLUSIONFor children with secondary coagulation disorders of unknown cause, intoxication of raticide should be considered. The administration of blood coagulation factors and vitamin K(1) are effective in early treatment, and the treatment period should be more than 2 months. The PT and APTT should be followed up. Vitamin K(1) should be stopped when PT and APTT are normal.

Blood Coagulation Disorders ; chemically induced ; diagnosis ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Rodenticides ; poisoning ; Vitamin K 1 ; administration & dosage ; therapeutic use

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.
4-Hydroxycoumarins/*poisoning ; Adult ; Aged ; Aged, 80 and over ; Anticoagulants/*poisoning ; Antifibrinolytic Agents/therapeutic use ; Environmental Exposure ; Female ; Hemorrhage/*chemically induced/diagnosis/drug therapy ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Republic of Korea ; Treatment Outcome ; Vitamin K 1/therapeutic use