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

BACKGROUNDS/AIMS: Vitamin K may plays a role in controlling hepatocellular carcinoma (HCC) cell growth. In this study, we intended to present 5-year experience of 72 patients receiving oral vitamin K with or without sorafenib. Its end-point was to evaluate the safety of combination therapy using sorafenib and vitamin K. METHODS: An interim analysis was performed as a single-arm cross-sectional study, including 72 HCC patients who underwent liver resection or transplantation and administered oral vitamin K2 alone (n=47) or with sorafenib (n=25). RESULTS: In all patients, administration of vitamin K2 analog 45 mg/day did not show any noticeable adverse side-effect during vitamin K therapy of 23.3+/-10.6 months, except for one patient who experienced skin rash at the third day of vitamin K therapy. In 25 patients receiving sorafenib and vitamin K for 6 months or longer, any noticeable adverse side-effect suspected of vitamin K origin was not identified yet. A small proportion of patients showed unexpectedly favorable anti-tumor effects after use of vitamin K with or without sorafenib. CONCLUSIONS: Because add-on of oral vitamin K did not increase the adverse side-effects of sorafenib, a combination therapy with these two agents appears to be worthy of further clinical trial with an expectation of synergistic therapeutic effects.
Carcinoma, Hepatocellular* ; Cross-Sectional Studies ; Exanthema ; Humans ; Liver ; Neoplasm Metastasis ; Vitamin K 2 ; Vitamin K*

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*

No abstract available.
Vitamin K Deficiency* ; Vitamin K* ; Vitamins*

No abstract available.
Vitamin K Deficiency* ; Vitamin K* ; Vitamins*

Several theories have been proposed to explain the etiology of adolescent idiopathic scoliosis (AIS) until present. However, limited data are available regarding the impact of vitamin D insufficiency or deficiency on scoliosis. Previous studies have shown that vitamin D deficiency and insufficiency are prevalent in adolescents, including AIS patients. A series of studies conducted in Hong Kong have shown that as many as 30% of these patients have osteopenia. The 25-hydroxyvitamin D3 level has been found to positively correlate with bone mineral density (BMD) in healthy adolescents and negatively with Cobb angle in AIS patients; therefore, vitamin D deficiency is believed to play a role in AIS pathogenesis. This study attempts to review the relevant literature on AIS etiology to examine the association of vitamin D and various current theories. Our review suggested that vitamin D deficiency is associated with several current etiological theories of AIS. We postulate that vitamin D deficiency and/or insufficiency affects AIS development by its effect on the regulation of fibrosis, postural control, and BMD. Subclinical deficiency of vitamin K2, a fat-soluble vitamin, is also prevalent in adolescents; therefore, it is possible that the high prevalence of vitamin D deficiency is related to decreased fat intake. Further studies are required to elucidate the possible role of vitamin D in the pathogenesis and clinical management of AIS.
Adolescent ; Bone Density ; Bone Diseases, Metabolic ; Calcifediol ; Fibrosis ; Hong Kong ; Humans ; Prevalence ; Scoliosis ; Vitamin D Deficiency ; Vitamin D ; Vitamin K ; Vitamin K 2 ; Vitamins

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*