Vitamin K Antagonists [VKA] are the most frequently used oral anticoagulants in clinical practice; however, many patients fail to achieve adequate anticoagulation control. We conducted a randomized, placebo controlled, double blind study of Vitamin K1 (200mcg per day, Swanson Vitamins) in a population with predominantly venous thromboembolism aimed at evaluating its effectiveness in improving anticoagulation control in unstable patients. This study also aimed to evaluate the impact that clinical variables, patient anticoagulation knowledge, and genetic polymorphisms in genes known to impact warfarin and Vitamin K metabolism [VKORC1, CYP4F2, CYP2C9] had on anticoagulation control and intervention effectiveness. A total of N=54 patients were enrolled in the study over 15 months [January 2009 to June 2010]. Change score analysis and multivariate linear regression modelling of anticoagulation control measures were performed. No statistically significant reduction was observed in the Vitamin K1 arm for percent time in therapeutic range; however, reduction was observed in standard deviation of INRs [Change Score Vitamin K = -0.259, p=0.0261; Regression Model 95% C.I Beta Vitamin K = 0.38 to -0.08] during the intervention period. Adjusting for treatment group allocation, independent predictors of increased INR standard deviation included: >5 alcoholic drinks per week [95% C.I Beta = 0.04 to 0.41], self-reported dosing errors [95% C.I Beta = 0.13 to 0.47], and missed INR appointments [95% C.I Beta = 0.002 to 0.05]

Vitamin K Antagonists [VKA] are the most frequently used oral anticoagulants in clinical practice; however, many patients fail to achieve adequate anticoagulation control. We conducted a randomized, placebo controlled, double blind study of Vitamin K1 (200mcg per day, Swanson Vitamins) in a population with predominantly venous thromboembolism aimed at evaluating its effectiveness in improving anticoagulation control in unstable patients. This study also aimed to evaluate the impact that clinical variables, patient anticoagulation knowledge, and genetic polymorphisms in genes known to impact warfarin and Vitamin K metabolism [VKORC1, CYP4F2, CYP2C9] had on anticoagulation control and intervention effectiveness. A total of N=54 patients were enrolled in the study over 15 months [January 2009 to June 2010]. Change score analysis and multivariate linear regression modelling of anticoagulation control measures were performed. No statistically significant reduction was observed in the Vitamin K1 arm for percent time in therapeutic range; however, reduction was observed in standard deviation of INRs [Change Score Vitamin K = -0.259, p=0.0261; Regression Model 95% C.I Beta Vitamin K = 0.38 to -0.08] during the intervention period. Adjusting for treatment group allocation, independent predictors of increased INR standard deviation included: >5 alcoholic drinks per week [95% C.I Beta = 0.04 to 0.41], self-reported dosing errors [95% C.I Beta = 0.13 to 0.47], and missed INR appointments [95% C.I Beta = 0.002 to 0.05]

Techn. Universiẗat, Diss., 2003--Berlin.

Vitamin K Antagonists [VKA] are the most frequently used oral anticoagulants in clinical practice; however, many patients fail to achieve adequate anticoagulation control. We conducted a randomized, placebo controlled, double blind study of Vitamin K1 (200mcg per day, Swanson Vitamins) in a population with predominantly venous thromboembolism aimed at evaluating its effectiveness in improving anticoagulation control in unstable patients. This study also aimed to evaluate the impact that clinical variables, patient anticoagulation knowledge, and genetic polymorphisms in genes known to impact warfarin and Vitamin K metabolism [VKORC1, CYP4F2, CYP2C9] had on anticoagulation control and intervention effectiveness. A total of N=54 patients were enrolled in the study over 15 months [January 2009 to June 2010]. Change score analysis and multivariate linear regression modelling of anticoagulation control measures were performed. No statistically significant reduction was observed in the Vitamin K1 arm for percent time in therapeutic range; however, reduction was observed in standard deviation of INRs [Change Score Vitamin K = -0.259, p=0.0261; Regression Model 95% C.I Beta Vitamin K = 0.38 to -0.08] during the intervention period. Adjusting for treatment group allocation, independent predictors of increased INR standard deviation included: >5 alcoholic drinks per week [95% C.I Beta = 0.04 to 0.41], self-reported dosing errors [95% C.I Beta = 0.13 to 0.47], and missed INR appointments [95% C.I Beta = 0.002 to 0.05]

Estudos sobre a vitamina K têm evidenciado seu papel na manutenção da saúde óssea e vascular. A atuação desta vitamina em tecidos extra-hepáticos não é considerada na recomendação dietética da DRI de 2001, sendo reconhecidas necessidades maiores para função óssea em pessoas acima dos 60 anos e em indivíduos que fazem uso de medicamentos antivitamina K. Visando colaborar com pesquisas futuras, onde o conhecimento do teor de vitamina K1 é relevante, além de contribuir com dados para Tabela Brasileira de Composição de Alimentos - TBCA-USP, o presente trabalho foi conduzido para determinação do teor de filoquinona (vitamina K1) de hortaliças consumidas na cidade de São Paulo. As hortaliças analisadas foram escolhidas após a conclusão de um inquérito alimentar realizado, com adultos e idosos, num projeto de pesquisa desenvolvido junto ao Departamento de Alimentos e Nutrição Experimental da FCF/USP visando a análise da ingestão diária de vitamina K. Desta forma, foram analisadas as hortaliças mais consumidas por esses grupos, submetidas ou não ao processo de cocção. Estas amostras foram adquiridas diretamente na CEAGESP - Companhia de Entrepostos e Armazéns Gerais de São Paulo. As metodologias empregadas na determinação da filoquinona (vitamina K1) foram extração e purificação pelo método líquido-líquido utilizando solventes orgânicos e quantificação através da Cromatografia Líquida de Alta Eficiência (CLAE). Os resultados mostraram que as amostras de hortaliças de colorações verdes mais escuras apresentaram os maiores teores da vitamina como: salsa 491,05 µg/100g; espinafre 375,01 µg/100g, quando comparados com as amostras de colorações verdes mais claras as quais como é o caso da alface americana 113,42 µg/100g e a couve-flor 32,55 µg/100g. A maioria das hortaliças analisadas apresentaram variações entre as diferentes épocas do ano e quando comparadas com dados da literatura. / Studies on vitamin K have shown its role in maintaining bone and vascular health. The role of this vitamin in extrahepatic tissues is not considered in the dietary recommendation of DRI 2001. Increased need for vitamin K intake is recognized for the bone function in people over age 60 and individuals who use anti-vitamin K drugs. Aiming at supporting future research, where knowledge of vitamin K1 is relevant, and contribute data to the Brazilian Table of Food Composition - TBCA-USP, this study was conducted to determine the level of phylloquinone (vitamin K1) of vegetables consumed in the city of São Paulo. The vegetables studied were chosen after completion of a nutrition survey carried out with adults and elderly people, a research project developed by the Department of Food and Experimental Nutrition FCF / USP aimed at analyzing the daily intake of vitamin K. Therefore, we analyzed the most consumed vegetables by these groups submitted or not to the cooking process. These samples were acquired directly at CEAGESP - General Warehouses Company of São Paulo. The methodologies employed in the determination of phylloquinone (vitamin K1) were extraction and purification method using liquid-liquid organic solvents followed by High Performance Liquid Chromatography (HPLC). The results showed that the samples of darker green vegetables showed the highest levels of vitamin such as parsley (491.05 µg/100g) and spinach (375.01 µg/100g), when compared with samples of lighter coloration (e.g. 113.42 µg/100g lettuce, and 32.55 µg/100g cauliflower). Most vegetables analyzed showed variation in results when compared to the different seasons and the literature data.

Estudos sobre a vitamina K têm evidenciado seu papel na manutenção da saúde óssea e vascular. A atuação desta vitamina em tecidos extra-hepáticos não é considerada na recomendação dietética da DRI de 2001, sendo reconhecidas necessidades maiores para função óssea em pessoas acima dos 60 anos e em indivíduos que fazem uso de medicamentos antivitamina K. Visando colaborar com pesquisas futuras, onde o conhecimento do teor de vitamina K1 é relevante, além de contribuir com dados para Tabela Brasileira de Composição de Alimentos - TBCA-USP, o presente trabalho foi conduzido para determinação do teor de filoquinona (vitamina K1) de hortaliças consumidas na cidade de São Paulo. As hortaliças analisadas foram escolhidas após a conclusão de um inquérito alimentar realizado, com adultos e idosos, num projeto de pesquisa desenvolvido junto ao Departamento de Alimentos e Nutrição Experimental da FCF/USP visando a análise da ingestão diária de vitamina K. Desta forma, foram analisadas as hortaliças mais consumidas por esses grupos, submetidas ou não ao processo de cocção. Estas amostras foram adquiridas diretamente na CEAGESP - Companhia de Entrepostos e Armazéns Gerais de São Paulo. As metodologias empregadas na determinação da filoquinona (vitamina K1) foram extração e purificação pelo método líquido-líquido utilizando solventes orgânicos e quantificação através da Cromatografia Líquida de Alta Eficiência (CLAE). Os resultados mostraram que as amostras de hortaliças de colorações verdes mais escuras apresentaram os maiores teores da vitamina como: salsa 491,05 µg/100g; espinafre 375,01 µg/100g, quando comparados com as amostras de colorações verdes mais claras as quais como é o caso da alface americana 113,42 µg/100g e a couve-flor 32,55 µg/100g. A maioria das hortaliças analisadas apresentaram variações entre as diferentes épocas do ano e quando comparadas com dados da literatura. / Studies on vitamin K have shown its role in maintaining bone and vascular health. The role of this vitamin in extrahepatic tissues is not considered in the dietary recommendation of DRI 2001. Increased need for vitamin K intake is recognized for the bone function in people over age 60 and individuals who use anti-vitamin K drugs. Aiming at supporting future research, where knowledge of vitamin K1 is relevant, and contribute data to the Brazilian Table of Food Composition - TBCA-USP, this study was conducted to determine the level of phylloquinone (vitamin K1) of vegetables consumed in the city of São Paulo. The vegetables studied were chosen after completion of a nutrition survey carried out with adults and elderly people, a research project developed by the Department of Food and Experimental Nutrition FCF / USP aimed at analyzing the daily intake of vitamin K. Therefore, we analyzed the most consumed vegetables by these groups submitted or not to the cooking process. These samples were acquired directly at CEAGESP - General Warehouses Company of São Paulo. The methodologies employed in the determination of phylloquinone (vitamin K1) were extraction and purification method using liquid-liquid organic solvents followed by High Performance Liquid Chromatography (HPLC). The results showed that the samples of darker green vegetables showed the highest levels of vitamin such as parsley (491.05 µg/100g) and spinach (375.01 µg/100g), when compared with samples of lighter coloration (e.g. 113.42 µg/100g lettuce, and 32.55 µg/100g cauliflower). Most vegetables analyzed showed variation in results when compared to the different seasons and the literature data.

A malária apresenta um alto índice de mortalidade com mais de 500 mil mortes registradas em 2013. Para agravar a situação de saúde pública, foi descrito o surgimento de resistência às drogas usadas na terapêutica da doença. Torna-se necessário a identificação e o estudo de novos alvos antimaláricos. A via MEP se mostra como um potencial alvo para o desenvolvimento de drogas contra P. falciparum uma vez que está ausente em humanos. Nossos objetivos foram avaliar a função da vitamina E biossintetizada pelo parasita, caracterizar a biossíntese de vitamina K1 e o metabolismo de fitol. Esse estudo determinou que a vitamina E biossintetizada pelo parasita atua no sistema redox do parasita. Por outro lado, mostramos que a biossíntese de vitamina K1 é ativa no parasita e detectamos sua forma reduzida. Por fim, observamos que existe uma via de reaproveitamento de fitol em P. falciparum assim como em plantas. O estudo abre oportunidades para um desenvolvimento racional de novos antimaláricos e aprofunda o conhecimento na biologia do parasita. / Malaria has the highest mortality rate with more than 500 000 deaths in 2013. The public health situation gets worse because it has been described the emergence of resistance to common drugs used in the treatment of disease. It is necessary to identify and study of new antimalarial targets. The MEP pathway is a potential target for drug development against Plasmodium falciparum once it is absent in humans. Our objectives were to evaluate the function of vitamin E biosynthesized by the parasite and characterize the biosynthesis of vitamin K1 and the phytol metabolism. This study determined that vitamin E biosynthesized by the parasite operates in the redox system of the parasite. We show the biosynthesis of vitamin K1 is active on parasite and we detected its reduced form. Finally, we demonstrate that there is a phytol salvage pathway in P. falciparum as well as plants. The study opens opportunities for the rational development of new antimalarials and deepens knowledge on parasite biology.

A malária apresenta um alto índice de mortalidade com mais de 500 mil mortes registradas em 2013. Para agravar a situação de saúde pública, foi descrito o surgimento de resistência às drogas usadas na terapêutica da doença. Torna-se necessário a identificação e o estudo de novos alvos antimaláricos. A via MEP se mostra como um potencial alvo para o desenvolvimento de drogas contra P. falciparum uma vez que está ausente em humanos. Nossos objetivos foram avaliar a função da vitamina E biossintetizada pelo parasita, caracterizar a biossíntese de vitamina K1 e o metabolismo de fitol. Esse estudo determinou que a vitamina E biossintetizada pelo parasita atua no sistema redox do parasita. Por outro lado, mostramos que a biossíntese de vitamina K1 é ativa no parasita e detectamos sua forma reduzida. Por fim, observamos que existe uma via de reaproveitamento de fitol em P. falciparum assim como em plantas. O estudo abre oportunidades para um desenvolvimento racional de novos antimaláricos e aprofunda o conhecimento na biologia do parasita. / Malaria has the highest mortality rate with more than 500 000 deaths in 2013. The public health situation gets worse because it has been described the emergence of resistance to common drugs used in the treatment of disease. It is necessary to identify and study of new antimalarial targets. The MEP pathway is a potential target for drug development against Plasmodium falciparum once it is absent in humans. Our objectives were to evaluate the function of vitamin E biosynthesized by the parasite and characterize the biosynthesis of vitamin K1 and the phytol metabolism. This study determined that vitamin E biosynthesized by the parasite operates in the redox system of the parasite. We show the biosynthesis of vitamin K1 is active on parasite and we detected its reduced form. Finally, we demonstrate that there is a phytol salvage pathway in P. falciparum as well as plants. The study opens opportunities for the rational development of new antimalarials and deepens knowledge on parasite biology.

The purpose of this study was to evaluate the stability of vitamin K1 oral liquids in Sterile Water for Injection when stored in amber glass bottles and amber plastic syringes under refrigerated conditions. Four 100-mL batches of vitamin K1 in Sterile Water for Injection were prepared in amber glass bottles to protect from light. One of the batches was divided into 1-mL aliquots, using amber plastic oral syringes, and capped. The prepared bottles and syringes were stored in a laboratory refrigerator. On each day of sampling, 1-mL aliquots were removed from each bottle and mixed with an equal volume of ethanol. Likewise, the contents of sample syringes were mixed with ethanol to achieve an assay concentration of 0.5 mg/mL. Recovery of vitamin K1 in the compounded samples was quantified against a United States Pharmacopeia reference standard. Quantification was achieved using a stability-indicating high-performance liquid chromatography with ultraviolent light detection method. Product stability is defined as 90% to 110% of the initial concentration. The percent recovery in the Sterile Water for Injection preparations in glass bottles remained above 90% for the 105-day duration of the study, but some samples stored in amber plastic syringes fell below 90% on day 21. Furthermore, a statistically significant difference (2-way ANOVA, P < 0.0001) emerged between syringes at day 0 and day 30, and this trend continued through the day 60, 90, and 105 samples. The only statistically significant difference found within the bottle-stored samples occurred on day 105 (versus zero, P = 0.0465), but the recovery on day 105 still exceeded 90%. Vitamin K1 in Sterile Water for Injection, stored in a refrigerated amber glass bottle, is stable for 105 days. This preparation can also be stored in amber plastic syringes, but this decreases the beyond-use date to 14 days.