Eficacia de la vitamina K en los trastornos de coagulación en los pacientes con enfermedad hepática crónica / Efficacy of vitamin K in coagulation disorders in patients with chronic liver disease

La coagulopatía es el denominador común en la amplia gama de procesos hepático crónicos, efecto principal de la deficiencia de vitamina K. A pesar de la falta de evidencia que sostiene su eficacia, su administración representa una parte del manejo de muchos pacientes con coagulopatía. Por tanto, el objetivo primario de este estudio fue comparar los tiempos de coagulación tras la administración de vitamina K en pacientes con enfermedad hepática crónica y trastornos de coagulación. Se postularon como secundarios la caracterización del paciente hepatópata según grupo nosológico por edad y sexo, así como las diferencias existentes entre las pruebas de coagulación basales con respecto a cada grupo. 72 pacientes fueron reclutados en 4 grupos, grupo 1: hepatitis B inactiva (n=6), grupo 2: hepatitis B crónica-hepatitis C (n=14), grupo 3: cirrosis (n=35) y grupo 4: hepatocarcinoma (n=17), se administraron 3 dosis de vitamina K de 10 mg cada una a intervalos de 24 horas, se midieron tiempo de protrombina (TP), radio normalizado internacional (INR) y tiempo de tromboplastina parcial activado (TPT) basales y cada 24 horas después de cada dosis. Se logró establecer una diferencia estadísticamente significativa en la corrección del tiempo de protrombina (31.04±9.62 a 21.69±8.48 P˂0.0001) así como del INR (2.81±1.013 a 1.92±0.81, P˂0.0001), hubo diferencia en cuanto a grupo diagnóstico y edad de presentación, así como en cuanto a tiempos de coagulación basales según diagnóstico. Por tanto, se demostró la efectividad de la vitamina K en la corrección del TP e INR.(AU)

Coagulopathy is the common denominator in the wide range of chronic liver processes, the main effect of vitamin K deficiency. Despite the lack of evidence supporting its efficacy, its administration represents a part of the management of many patients with coagulopathy. Therefore, the primary objective of this study was to compare clotting times after vitamin K administration in patients with chronic liver disease and coagulation disorders. The characterization of the liver disease patient according to nosological group by age and sex, as well as the differences between the baseline coagulation tests with respect to each group, were postulated as secondary. 72 patients were recruited into 4 groups, group 1: inactive hepatitis B (n = 6), group 2: chronic hepatitis B-hepatitis C (n = 14), group 3: cirrhosis (n = 35) and group 4: hepatocarcinoma ( n = 17), 3 doses of vitamin K of 10 mg each were administered at 24-hour intervals, prothrombin time (TP), international normalized radius (INR) and baseline activated partial thromboplastin time (TPT) were measured and each 24 hours after each dose. It was possible to establish a statistically significant difference in the correction of prothrombin time (31.04 ± 9.62 to 21.69 ± 8.48 P˂0.0001) as well as the INR (2.81 ± 1.013 to 1.92 ± 0.81, P˂0.0001), there was a difference in terms of group Diagnosis and age of presentation, as well as baseline clotting times according to diagnosis. Therefore, the effectiveness of vitamin K in the correction of TP and INR was demonstrated

Avaliação da atividade anti-trypanosoma cruzi in vitro e in vivo de derivados de vitamina K / Evaluation of anti-Trypanosoma cruzi activity in vitro and in vivo derivatives of vitamin K

A doença de Chagas (DC) é considerada um agravo ainda negligenciado. Atualmente, estima-se cerca de 10 milhões de pessoas infectadas pelo Trypanosoma cruzi, em todo o mundo, principalmente na América Latina. Sabe-se que alguns derivados de naftoquinonas podem agir sobre a tripanotiona redutase (TR), enzima específica dos tripanossomatídeos responsável pelo controle oxidativo celular. A inibição da TR favorece um processo oxidativo e morte do protozoário. Este trabalho teve como objetivo investigar o potencial anti-T.cruzi da fitomenadiona, (K1) e menadiona (K3), ambas vitaminas K derivadas de naftoquinonas. Com este propósito, o efeito tripanocida de K1 e K3 foi avaliado através de ensaios in vitro com as formas tripomastigotas e epimastigotas do T. cruzi nas cepas Colombiana e Y utilizando os testes de inibição, citotoxicidade dos compostos, ensaio de infecção em macrófagos, avaliação de alterações ultraestruturais, bem como ensaio em in vivo para avaliação na redução da parasitemia. Os valores de IC50 mais significativos para formas tripomastigotas do T. cruzi foram 27,55 μM para K1, 2,19 μM para K3 e 12,46 μM para o benzonidazol, a droga padrão. Contudo, o tratamento com a vitamina K1 não reduziu a parasitemia in vivo, que permaneceu alta assim como a do controle tratado com veículo. A vitamina K3 foi capaz de inibir ambas as cepas e diferentes formas do parasito em ensaios in vitro. No ensaio de infecção de macrófagos, a vitamina K3 em concentração de 21,4 μM inibiu de forma mais significativa a infecção de células em relação à droga padrão, em concentração de 38,4 μM. Apesar da citotoxicidade mais elevada, esta droga apresentou uma seletividade maior ao parasito do que a células de mamíferos e, em baixas doses, causou a redução na parasitemia in vivo. As avaliações ultraestruturais por microscopia eletrônica de transmissão evidenciaram alterações celulares induzidas por estes compostos, destacando-se a tumefação do cinetoplasto e a presença de vacúolos. A quantificação ultraestrutural na avaliação por microscopia eletrônica de varredura demonstrou alterações em cerca de 80% dos parasitos observados quando tratados com K3 a 5 μM. Nossos resultados demonstram o efeito anti-T. cruzi das moléculas testadas e sugerem que estas possam servir de base para o desenho de novos compostos candidatos a fármacos para o tratamento da doença de Chagas.

Comparison of the Effect of Vitamin K2 and Risedronate on Trabecular Bone in Glucocorticoid-Treated Rats: A Bone Histomorphometry Study

PURPOSE: To compare the effect of vitamin K2 and risedronate on trabecular bone in glucocorticoid (GC)-treated rats. MATERIALS AND METHODS: Forty-eight Sprague-Dawley female rats, 3 months of age, were randomized by the stratified weight method into 5 groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K2, risedronate, or vitamin K2 + risedronate. GC (methylprednisolone sodium succinate, 5.0 mg/kg) and risedronate (10 microgram/kg) were administered subcutaneously three and five times a week, respectively. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally three times a week. At the end of the 8-week experiment, bone histomorphometric analysis was performed on trabecular bone of the tibial proximal metaphysis. RESULTS: GC administration decreased trabecular bone mass compared with age-matched controls because of decreased bone formation (mineralizing surface, mineral apposition rate, and bone formation rate) and increased bone erosion. Vitamin K2 attenuated GC-induced trabecular bone loss by preventing GC-induced decrease in bone formation (mineralizing surface) and subsequently reducing GC-induced increase in bone erosion. Risedronate prevented GC-induced trabecular bone loss by preventing GC-induced increase in bone erosion although it also suppressed bone formation (mineralizing surface, mineral apposition rate, and bone formation rate). Vitamin K2 mildly attenuated suppression of bone formation (mineralizing surface) and bone erosion caused by risedronate without affecting trabecular bone mass when administered in combination. CONCLUSION: The present study showed differential effect of vitamin K2 and risedronate on trabecular bone in GC-treated rats.

Differential Effect of Vitamin K and Vitamin D Supplementation on Bone Mass in Young Rats Fed Normal or Low Calcium Diet

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25microgram/100 g, food intake), or vitamin K + vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.

In vitro stimulation of microsomal diethyl nitrosamine deethylase activity by vitamin K3 (menadione).

Vitamin K3 (menadione) has been found to stimulate diethyl nitrosamine (DEN)-deethylase activity in rat liver microsomes. The vitamin also takes care of the inhibitory effect of the anaerobic conditions as well as those of cytochrome poisons like sodium azide and sodium cyanide, possibly through production of active oxygen species. The enzyme was also stimulated by H2O2 and SOD and inhibited by catalase, thereby suggesting that H2O2 or some derivatives of it may be the active oxygen species involved in the reaction.

Growth of Mycobacterium leprae in a redox system: II. Further improvements in the system and growth efficiency.

Improvement of the Redox System for growth of M. leprae as brought about by modification in the concentration and mode of preparation of individual media constituents, and by addition of newer substances, is being reported. A structural modification in the construction of the Thunberg's tubes and flasks that are used as culture vessels, has been introduced for ease of handling. Vitamin E (alpha-tocopherol) has been found to be useful. Concentrations of Liposomes and Gelatin in the medium could be reduced by at least five folds, considerably easing thereby smearing and harvesting of cultures. Dimercaptopropanol British Anti-lewisite or BAL) has been used, but its usefulness or otherwise is yet to be determined conclusively. The basis of intracellular parasitism of M. leprae has been discussed.

Efecto de la vitamina K3 (Menadiona) sobre el contenido hepático de electrolitos / Effect of vitamin K3 (Menadione) on the hepatic content of electrolytes

Se realizaron una serie de experimentos en ratas machos Sprague Dowley para estudiar la importancia de la vitamina K3 en la distribución electrolítica hepática. En este sentido se evaluó el contenido hepático de Fe, Pi, Mg, Mn, Ca, Cu, Na, K, Zn y Cl en ratas tratadas con dosis crecientes de vitamina K3, y los datos se correlacionaron con los niveles obtenidos en el grupo control respectivo. La administración de dosis de 10 a 50 mg/kg de peso únicamente tuvo un efecto significativo en el incremento de Fe. No se observaron variaciones significativas de los demás electrólitos. Los resultados obtenidos permiten sugerir algunas posibilidades sobre la variación del contenido de hierro