RESUMEN
High salt (HS) intake can lead to hypertension, probably the result of the predominance of vasoconstrictor reactive oxygen species over vasodilator nitric oxide (NO). We aimed to examine if the supposed NO deficiency and the resultant blood pressure increase could be corrected by supplementation of L-arginine, the substrate, and tetrahydrobiopterin (BH4), a co-factor of NO synthases. Wistar rats without known genetic background of salt sensitivity were exposed to HS diet (4%Na) for 10 or 26 days, without or with supplementation with oral L-arginine, 1.4 mg/kg b.w. daily, alone or together with intraperitoneal BH4, 10 mg/kg daily. Systolic blood pressure (SBP, tail-cuff method) was measured repeatedly and found to increase ~40 mmHg after 26 days; L-arginine and BH4 did not significantly attenuate this increase. At the end of chronic studies, in anaesthetized rats the diet- and treatment-induced changes in renal haemodynamics were assessed. HS diet selectively decreased (-30%, P < 0.03) the inner medullary blood flow (IMBF, laser-Doppler flux) without changing total or cortical renal perfusion. Arginine supplementation tended to raise all renal circulatory parameters, and distinctly increased IMBF, to 61% above the HS diet level (P < 0.05). In conclusion, unlike in confirmed genetically determined salt-dependent hypertension, L-arginine and BH4 supplementation failed to attenuate the SBP increase observed after exposure to HS diet. On the other hand, arginine increased total and regional renal perfusion, especially IMBF. This suggests that the delivery of arginine increased intrarenal NO synthesis, an action of renoprotective potential which presumably countered the harmful influence of the local tissue oxidative stress.
Asunto(s)
Arginina/farmacología , Biopterinas/análogos & derivados , Presión Sanguínea/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipotensión/inducido químicamente , Cloruro de Sodio Dietético/administración & dosificación , Animales , Arginina/efectos adversos , Biopterinas/efectos adversos , Biopterinas/farmacología , Suplementos Dietéticos , Hipertensión/metabolismo , Hipotensión/metabolismo , Riñón , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Circulación Renal/efectos de los fármacosRESUMEN
We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/l). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 % at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 %). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Benzoatos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Indoles/uso terapéutico , Insuficiencia Renal/prevención & control , Urea/análogos & derivados , Animales , Fístula Arteriovenosa , Benzoatos/farmacología , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Epóxido Hidrolasas/antagonistas & inhibidores , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Masculino , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Insuficiencia Renal/etiología , Urea/farmacología , Urea/uso terapéuticoRESUMEN
The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue.
Asunto(s)
Benzoatos/uso terapéutico , Epóxido Hidrolasas/antagonistas & inhibidores , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Renal/prevención & control , Urea/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/sangre , Ácido 8,11,14-Eicosatrienoico/metabolismo , Angiotensina I/sangre , Angiotensina II/sangre , Inhibidores de la Enzima Convertidora de Angiotensina , Animales , Benzoatos/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Compuestos Epoxi/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico por imagen , Riñón/metabolismo , Masculino , Miocardio/metabolismo , Fragmentos de Péptidos/sangre , Distribución Aleatoria , Ratas , Insuficiencia Renal/sangre , Insuficiencia Renal/etiología , Sistema Renina-Angiotensina/efectos de los fármacos , Ultrasonografía , Urea/farmacología , Urea/uso terapéuticoRESUMEN
AIM: We studied a possible action of nitric oxide (NO), an intrarenal vasodilator, to buffer a decrease in renal perfusion induced by electrical stimulation of renal nerves (RNS). METHODS: In anaesthetized rats RNS was performed (15 V, 2 ms pulse duration) for 10 s at the frequencies of 2, 3.5, 5 and 7.5 Hz. The total renal blood flow (RBF), an index of cortical perfusion, was measured using a Transonic probe on the renal artery. The outer and inner medullary blood flow (OMBF, IMBF) was measured by laser-Doppler flowmetry. The effect of RNS on RBF, OMBF and IMBF was determined in rats which were either untreated or pre-treated with L-NAME (0.6 or 1.8 mg kg(-1) i.v.), or S-methyl thiocitrulline (SMTC, 20 microg kg(-1) min(-1) i.v.), a selective inhibitor of neuronal NO synthase (nNOS). RESULTS: In untreated rats, RNS decreased IMBF significantly less than RBF and OMBF. High-dose L-NAME treatment significantly enhanced the RNS induced decrease of RBF but not of OMBF or IMBF. SMTC treatment significantly enhanced the decrease of IMBF, without affecting the response of RBF or OMBF. CONCLUSION: At intact NO synthesis the inner medullary circulation is not controlled by renal nerves to the extent observed for the outer medulla or cortex. NO generated by all NOS isoforms present in the kidney buffers partly the intrarenal vasoconstriction triggered by electrical RNS. The NO derived from nNOS seems of particular importance in the control of inner medullary perfusion, interacting with NO generated by endothelial NOS and renal nerves.
Asunto(s)
Citrulina/análogos & derivados , Riñón/fisiología , Óxido Nítrico Sintasa/metabolismo , Circulación Renal/fisiología , Tiourea/análogos & derivados , Animales , Citrulina/farmacología , Estimulación Eléctrica/métodos , Inhibidores Enzimáticos/farmacología , Riñón/efectos de los fármacos , Riñón/inervación , Médula Renal/fisiología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Ratas , Ratas Wistar , Circulación Renal/efectos de los fármacos , Tiourea/farmacología , Vasodilatadores/farmacologíaRESUMEN
AIM: The prostaglandin cyclooxygenase (COX) and P450 cytochrome (CYP450) pathways of arachidonic acid metabolism are functionally interrelated and both engaged in control of sodium excretion; the study focused on their contribution to the natriuresis which follows hypertonic saline infusion in the rat. METHODS: In anaesthetized rats, clearance studies were conducted, supplemented with laser-Doppler measurements of the cortical and medullary blood flow (CBF, MBF), and measurement of medullary tissue admittance (Y), an index of interstitial ion concentration. RESULTS: Indomethacin (Indo), 5 mg kg(-1) i.v. paradoxically enhanced the natriuresis secondary to intra-aortic suprarenal 5% saline load, further increasing sodium excretion by 385 +/- 73% (P < 0.01). After acute clotrimazole, 10 mg kg(-1) i.v. an inhibitor of CYP450 epoxygenase, the increase in natriuresis was smaller and did not differ from that observed after the drug's ethanol solvent. In rats pre-treated with clotrimazole for 3 days, hypertonic saline loading increased sodium excretion (U(Na)V) to 0.94 +/- 0.22 micromol min(-1) , compared with a significantly greater (P < 0.05) increase to 2.76 +/- 0.48 micromol min(-1) measured in untreated controls. Indo increased U(Na)V twofold, similarly in the clotrimazole and in the control group; in the absence or presence of clotrimazole treatment, COX blockade significantly decreased MBF and increased Y. CONCLUSION: The data indicate that blockade of the CYP450 epoxygenase significantly impairs excretion of sodium in rats acutely loaded with hypertonic NaCl solution. The paradoxical post-Indo natriuresis is preserved in clotrimazole treated rats, which speaks against the role of CYP450 pathway in the response.
Asunto(s)
Sistema Enzimático del Citocromo P-450/fisiología , Natriuresis/fisiología , Prostaglandina-Endoperóxido Sintasas/fisiología , Animales , Clotrimazol/farmacología , Indometacina/farmacología , Infusiones Intraarteriales/métodos , Riñón/efectos de los fármacos , Riñón/fisiología , Masculino , Prostaglandinas/biosíntesis , Ratas , Ratas Wistar , Circulación Renal/fisiología , Solución Salina Hipertónica/administración & dosificaciónRESUMEN
The potential mechanism underlying the rapid response to vitamin K replacement in acquired deficiency states is incompletely understood. To examine vitamin K metabolism, a 10-year-old boy with autoimmune enteropathy on oral vitamin K supplementation, who presented with profuse nosebleeds and calf tenderness, was evaluated. Laboratory analyses were consistent with severe vitamin K deficiency: vitamin K dependent protein (VKDP) levels < 5%, normal vitamin K epoxide level and depressed total prothrombin antigen (carboxylated and undercarboxyated forms). Intramuscular vitamin K (10 mg) was administered. Nine hours following therapy, VKDP levels corrected completely. Total prothrombin antigen increased indicating new prothrombin synthesis. However, the increase in the prothrombin-clotting assay far exceeded the increase in total prothrombin, supporting storage of undercarboxylated prothrombin in vitamin K deficiency states, with carboxylation and secretion after vitamin K replacement. Although this mechanism is known to occur in rodents, it has not been reported in humans. Our findings suggest a new potential mechanism of prothrombin metabolism in humans.
Asunto(s)
Protrombina , Deficiencia de Vitamina K , Coagulación Sanguínea , Niño , Humanos , Masculino , Deficiencia de Vitamina K/sangreRESUMEN
Gender differences in relation to vitamin K were investigated in the rat. Hepatic phylloquinone and menaquinone (MK-1 to MK-10) concentrations, gamma-carboxyglutamic acid (Gla) excretion, plasma phylloquinone and percent prothrombin were measured in male and female rats on a chow diet (24.5 ng phylloquinone and 8.8 microgram menadione), and on phylloquinone-deficient and -supplemented purified diets (0.38 and 1400 ng phylloquinone/g, respectively). Mean hepatic phylloquinone concentrations varied with dietary intake and ranged from 6.8+/-9.0 pmol/g in the deficient male, to 171. 1+/-56.9 pmol/g in the supplemented female. Menaquinones accounted for a large proportion of total vitamin K in the liver of males and females with MK-4, MK-6, and MK-10 present in highest concentrations. On the chow and supplemented diets, females had significantly higher MK-4, MK-6, and MK-10 concentrations in their livers (P<0.05). On the phylloquinone-deficient diet (-K1), hepatic phylloquinone, MK-4, and to a lesser extent MK-6 (but not MK-10) were significantly reduced (P<0.05). In the phylloquinone-supplemented male and female groups, which did not receive menadione during the experimental period, MK-4 increased above that in the chow groups suggesting synthesis of MK-4 from phylloquinone which was statistically significant in the female (P<0.01). A significant gender difference (P<0.05) was also observed for urinary Gla excretion with less Gla excreted by the females indicating that females may require less dietary phylloquinone than males of the same body weight.
Asunto(s)
Hígado/metabolismo , Vitamina K 1/metabolismo , Deficiencia de Vitamina K/metabolismo , Vitamina K/farmacología , Ácido 1-Carboxiglutámico/orina , Animales , Cromatografía Líquida de Alta Presión , Dieta , Humanos , Masculino , Protrombina/análisis , Ratas , Ratas Sprague-Dawley , Factores Sexuales , Vitamina K/administración & dosificación , Vitamina K/análogos & derivados , Vitamina K 1/sangre , Vitamina K 1/deficiencia , Vitamina K 2/análogos & derivadosRESUMEN
The purpose of this study was to characterize the absorption and transport of phylloquinone (vitamin K1) by plasma lipoproteins. Twenty-six healthy subjects (11 men and 15 women) aged 20-78 y received phylloquinone in the amount of either 1.43 or 50 microg/kg body wt orally with a fat-rich meal containing 1.0 g/kg body wt of fat, carbohydrate, and protein and 7.0 mg cholesterol/kg body wt. Blood was obtained at baseline (0 h) and 3, 6, 9, and 12 h after the meal for the measurement of plasma lipid and phylloquinone concentrations in plasma and lipoprotein subfractions. In both groups of subjects, triacylglycerol concentrations peaked after 3 h in plasma and in the triacylglycerol-rich lipoprotein fraction, composed of chylomicrons and VLDLs. Plasma phylloquinone concentrations peaked at 6 h. At baseline and during the postprandial phase, > 53% of plasma phylloquinone was carried by the triacylglycerol-rich lipoprotein fraction. In 9 of the 11 subjects supplemented with 50 microg phylloquinone/kg, plasma lipoproteins were isolated by sequential ultracentrifugation. In these subjects the fraction of plasma phylloquinone carried by LDLs and by HDLs increased progressively from 3% and 4% at 3 h to 14% and 11% at 12 h, respectively. Our data indicate that whereas triacylglycerol-rich lipoproteins are the major carriers of phylloquinone, LDL and HDL may carry small fractions of this vitamin.
Asunto(s)
Antifibrinolíticos/sangre , Antifibrinolíticos/farmacocinética , Grasas de la Dieta/metabolismo , Lipoproteínas/sangre , Vitamina K 1/farmacocinética , Administración Oral , Adulto , Anciano , Antifibrinolíticos/administración & dosificación , Transporte Biológico , Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Femenino , Humanos , Absorción Intestinal , Lipoproteínas/administración & dosificación , Lipoproteínas/fisiología , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , Vitamina K 1/administración & dosificación , Vitamina K 1/sangreRESUMEN
A diurnal variation exists in blood levels of the vitamin K-dependent bone protein osteocalcin. However, it is not known whether the carboxylated and undercarboxylated constituents of osteocalcin also vary. Therefore, osteocalcin and undercarboxylated osteocalcin were measured in specimens collected every 4 hours over a 24-hour period in nine healthy subjects (five males, four females) ages 20-33 years who were consuming a mixed diet containing 100 microg of phylloquinone. Osteocalcin and undercarboxylated osteocalcin were measured by radioimmunoassay (RIA) before and after treatment with barium sulfate. Although the percent undercarboxylated osteocalcin did not change, a diurnal variation was observed in total osteocalcin, carboxylated osteocalcin, and undercarboxylated osteocalcin, with peak concentrations at 4 a.m. and the lowest concentrations between 12 p.m. and 4 p.m. The difference between the total osteocalcin peak and trough concentrations averaged 28 +/- 7 (SEM)%. There were no gender differences in these rhythms. The effect of dietary phylloquinone as a modulator of these rhythms was evaluated in a randomized study by increasing phylloquinone intake to 420 microg/day with fortified corn oil, split between the lunch and dinner meals. Total and carboxylated osteocalcin fluctuations and concentrations were not affected by the dietary treatment. The diurnal variation in undercarboxylated osteocalcin was abolished with supplementation and concentrations at 8 a.m. (14 hours following supplementation) (2.3 +/- 0.2 ng/ml) were significantly lower than the unsupplemented levels (2.7 +/- 0.2 ng/mL, P = 0.006). The percentage of undercarboxylated osteocalcin was similarly decreased after supplementation (19.7 +/- 1.3%) in relation to the mixed diet cycle (24.2 +/- 1.6%, P = 0.006) at 8 a.m. on the second day. Dietary supplementation induced a fluctuation in percentage undercarboxylated osteocalcin with a decline in levels starting at approximately 12 a.m. Therefore, additional dietary phylloquinone does not appear to modulate the total osteocalcin diurnal rhythm, but can influence its undercarboxylated component.
Asunto(s)
Ritmo Circadiano , Osteocalcina/sangre , Vitamina K 1/farmacología , Vitamina K 1/farmacocinética , Adulto , Disponibilidad Biológica , Dieta , Femenino , Hemólisis , Humanos , Masculino , Osteocalcina/análogos & derivados , Osteocalcina/efectos de los fármacos , Radioinmunoensayo , Vitamina K 1/administración & dosificaciónRESUMEN
BACKGROUND: Patients with cystic fibrosis are at risk for impaired vitamin K status due to fat malabsorption from pancreatic insufficiency. This study was designed to assess vitamin K status and measure the effect of vitamin K1 supplementation in cystic fibrosis patients. METHODS: Eighteen outpatients participated in a crossover study to determine the effect of vitamin K1 (phylloquinone) supplementation. After obtaining initial data, each subject was randomly assigned to either a 4-week study treatment of 5 mg oral vitamin K1 supplementation per week, or no supplementation and then crossed over to the other treatment for a second 4 week period. Plasma, serum and urine samples were collected and analyzed pre-study and at the end of each study period. RESULTS: The mean concentration of plasma vitamin K1 for the supplemented group was significantly higher than the unsupplemented group, [0.34 nmol/L and 0.21 nmol/L, respectively (p < 0.05)]. The percent of undercarboxylated osteocalcin increased on supplementation from 17% to 31%, (p < 0.005). Prothrombin induced in vitamin K absence (PIVKA-II) increased on supplementation from 5 ng/mL to 22 ng/mL, (p < 0.005). The ratio of urinary gamma-carboxyglutamic acid/creatinine was similar for both study periods. CONCLUSIONS: In contrast to other studies in cystic fibrosis, this study demonstrated a need for vitamin K1 supplementation. The carboxylation state of osteocalcin and PIVKA-II were the most sensitive indices of changes in vitamin K1 status. Although the 5 mg vitamin K1/week dose improved these vitamin K parameters, normal levels were not achieved.
Asunto(s)
Biomarcadores , Fibrosis Quística/sangre , Fibrosis Quística/dietoterapia , Vitamina K 1/administración & dosificación , Vitamina K 1/sangre , Ácido 1-Carboxiglutámico/efectos de los fármacos , Ácido 1-Carboxiglutámico/orina , Administración Oral , Adolescente , Adulto , Creatinina/orina , Estudios Cruzados , Fibrosis Quística/orina , Registros de Dieta , Femenino , Humanos , Masculino , Osteocalcina/sangre , Osteocalcina/efectos de los fármacos , Estudios Prospectivos , Precursores de Proteínas/análisis , Precursores de Proteínas/efectos de los fármacos , Protrombina/análisis , Protrombina/efectos de los fármacos , Vitamina K 1/análogos & derivadosRESUMEN
The response of osteocalcin and other biochemical markers of vitamin K status to diets formulated to contain different amounts of phylloquinone was assessed in nine healthy subjects aged 20-33 y. Subjects resided in a metabolic ward for two 15-d cycles with a minimum of 6 wk between cycles. A mixed diet containing 100 micrograms phylloquinone/d was fed throughout both cycles; however, the phylloquinone content of one of the cycles was increased to a total of 420 micrograms/d on days 6 through 10 by fortifying corn oil in the diet with phylloquinone (supplemented diet). Total serum osteocalcin concentrations were not affected by either of the dietary treatments. The percentage of undercarboxylated osteocalcin increased an average of 28% over the 15-d cycle with the mixed diet (P < 0.05) and declined significantly an average of 41% with 5 d of the supplemented diet (day 6: 21.9 +/- 1.3%, day 11: 12.8 +/- 1.1%; P = 0.0001) with a rise after the return to the mixed diet (16.7 +/- 1.3%, P < 0.001). Plasma phylloquinone concentrations increased significantly with supplementation (day 6: 0.95 +/- 0.16 nmol/L, day 11: 1.40 +/- 0.29 nmol/L; P < 0.001) and then rapidly returned to presupplementation concentrations on returning to the mixed diet. Twenty-four-hour ratios of urinary gamma-carboxyglutamic acid to creatinine were unchanged with the supplemented diet; however, excretion declined to 91 +/- 2% of baseline after 10 d on the mixed diet (P = 0.01). These results show that undercarboxylated osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid excretion appear to be sensitive measures of vitamin K nutritional status because all of these variables were responsive to changes in dietary intake.
Asunto(s)
Ácido 1-Carboxiglutámico/orina , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/sangre , Dieta , Osteocalcina/sangre , Vitamina K 1/administración & dosificación , Vitamina K 1/sangre , Vitamina K/fisiología , Adulto , Femenino , Humanos , Masculino , Estado Nutricional , Tiempo de ProtrombinaAsunto(s)
Análisis de los Alimentos/métodos , Vitamina K 1/análisis , Cromatografía Líquida de Alta Presión/métodos , Humanos , Indicadores y Reactivos , Lactante , Alimentos Infantiles/análisis , Leche Humana/química , Aceites de Plantas/análisis , Estados Unidos , United States Food and Drug Administration , Verduras/químicaRESUMEN
Dihydro-vitamin K1 is a dietary form of vitamin K1 (phylloquinone) produced during the hydrogenation of vegetable oils. To determine if dihydro-vitamin K1 is present in plasma following dietary intake of a hydrogenated fat, eight healthy adults consumed each of two diets containing 30% of calories from fat, of which 20% was either soybean oil or a partially hydrogenated soybean oil-based stick margarine. Of the fats and oils analyzed, dihydro-vitamin K1 was only found in the hydrogenated products. The soybean oil diet contained 180 +/- 12 micrograms (mean +/- SD) of vitamin K1/day and nondetectable levels of dihydro-vitamin K1, whereas the stick margarine diet contained 199 +/- 7 micrograms of vitamin K1/day and 23 +/- 2 micrograms of dihydro-vitamin K1/day. After consuming each diet for five weeks, plasma dihydro-vitamin K1 concentrations were higher (P = 0.002) in all eight subjects when consuming the stick margarine diet (0.56 +/- 0.33 nmol/L) compared to the soybean oil diet (0.12 +/- 0.11 nmol/L). There was no significant change in plasma vitamin K1 concentrations when the two diets were compared. In conclusion, dihydro-vitamin K1 is detectable in plasma following dietary intake of a hydrogenated vitamin K1-rich vegetable oil.
Asunto(s)
Grasas de la Dieta/farmacocinética , Vitamina K 1/análogos & derivados , Vitamina K 1/farmacocinética , Anciano , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/sangre , Ingestión de Alimentos , Grasas/química , Femenino , Humanos , Hidrogenación , Masculino , Persona de Mediana Edad , Aceite de Soja/química , Aceite de Soja/metabolismo , Espectrometría de Fluorescencia , Vitamina K 1/administración & dosificación , Vitamina K 1/sangreRESUMEN
Dihydro-vitamin K1 was recently identified as a dietary form of vitamin K produced during the hydrogenation of vitamin K1-rich vegetable oils. Dihydro-vitamin K1 is absorbed, with measurable levels in human plasma following dietary intake. To determine the primary food sources of dihydro-vitamin K1 in the American diet, 261 foods from the U.S. Food and Drug Administration's (FDA) Total Diet Study (TDS) were analyzed by high-performance liquid chromatography. Of these foods, 36 contained dihydro-vitamin K1. Fast-food items that were otherwise poor sources of vitamin K1, such as french fries and fried chicken, contained appreciable amounts of dihydro-vitamin K1 (36 and 18 micrograms/100 g, respectively). These nutrient values were then applied to the FDA TDS consumption model to determine average dietary intake of dihydro-vitamin K1 in 14 age-gender groups. With the exception of infants, all age-gender groups had estimated mean daily dihydro-vitamin K1 intakes of 12-24 micrograms, compared to mean daily vitamin K1 intakes of 24-86 micrograms. The vitamin K1 and dihydro-vitamin K1 intakes were summed, and the dietary contribution of dihydro-vitamin K1 was expressed as a percentage of total vitamin K intake. Children reported the highest intakes of dihydro-vitamin K1 (30% of total vitamin K intake), followed by a progressive decrease in percentage contribution with age. There are currently no data on the relative bioavailability of dihydro-vitamin K1 but given its abundance in the American diet, this hydrogenated form of vitamin K warrants further investigation.
Asunto(s)
Grasas de la Dieta/administración & dosificación , Ingestión de Alimentos , Vitamina K 1/análogos & derivados , Vitamina K/química , Vitamina K/metabolismo , Adolescente , Adulto , Anciano , Animales , Pollos , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Femenino , Análisis de los Alimentos , Manipulación de Alimentos , Humanos , Hidrogenación , Lactante , Masculino , Persona de Mediana Edad , Solanum tuberosum , Estados Unidos , Vitamina K 1/administración & dosificaciónRESUMEN
Prenatal maternal vitamin K1 supplementation to improve the hemostatic status of the fetus may depend upon the route of administration and subsequent presentation at the placental barrier. We investigated intramuscular (IM) vs oral (PO) vitamin K1 supplementation in eight healthy, nonpregnant women of childbearing age. Pharmacokinetics were studied in each subject after a 5 mg IM dose and after a 5 mg oral dose of vitamin K1 approximately one month later. Plasma collected at the peak vitamin K level for each treatment was separated into very low density lipoproteins (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein-free fractions by density gradient ultracentrifugation. Vitamin K1 was measured in the plasma and lipoprotein fractions using HPLC. The concentration of vitamin K1 in plasma reached a peak 2 h after an IM dose and remained high throughout the 30 h course of the study. In contrast, the oral dose of vitamin K1 peaked at 4 h and rapidly decreased to near baseline by 18 to 30 h. The distribution of vitamin K1 in the lipid fractions was different for IM compared to PO. The percentage of vitamin K1 in the VLDL fraction at the peak for an oral dose was significantly higher than for an IM dose (80.8% +/- 3.5 vs 10.8% +/- 6.5, p < 0.0001). After the oral absorption stage, the subjects took 5 mg of vitamin K1 orally, once a day, for 12 days. No significant differences were observed for the following coagulation proteins and hemostatic markers measured immediately before and after long-term oral vitamin K supplementation: factor II, factor VII, protein C, and thrombin-antithrombin III complex. In conclusion, physiological processing of supplemented vitamin K1 differs in the IM vs PO routes of administration and 12 days of oral vitamin K1 does not alter the concentration of selected vitamin K-dependent coagulation proteins or thrombin-antithrombin complex generation.
Asunto(s)
Hemostasis/efectos de los fármacos , Lipoproteínas/sangre , Vitamina K 1/farmacocinética , Administración Oral , Adulto , Fraccionamiento Químico , Femenino , Humanos , Inyecciones Intramusculares , Vitamina K 1/administración & dosificaciónRESUMEN
OBJECTIVE: To examine the relationship between dietary phylloquinone intake and vitamin K status of postmenopausal Caucasian women. DESIGN: Cross-sectional study, in which dietary intake was estimated using weighed record techniques and vitamin K status was measured by a single plasma phylloquinone concentration and 24-h urinary gamma-carboxyglutamic acid (Gla) excretion. SETTING: The metabolic research unit at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA. SUBJECTS: 402 healthy postmenopausal Caucasian women who were participating in a randomized trial to determine the effect of calcium supplementation on bone loss. Of the original group, 362 had complete weighed diet records, 358 had corresponding plasma phylloquinone concentrations, and 346 had corresponding urinary Gla measurements. RESULTS: There was a significant correlation (r = 0.13, P = 0.01) between total dietary intake of phylloquinone (geometric mean = 89 micrograms/day) and plasma phylloquinone levels (mean = 1.12 nmol/l). Dietary intake was neither correlated with urinary Gla excretion (mean = 4.0 mumol/mmol creatinine) nor did it vary by season. The ratio of intra- to interindividual variance in phylloquinone intake was 2.6, from which it was estimated that 5 days of independent recording is necessary to estimate true usual dietary intake, assuming a correlation of 0.8. CONCLUSIONS: A weighed record has the potential to be a reliable method for estimating dietary intakes of vitamin K which relate to plasma phylloquinone levels used as an indicator of vitamin K status in postmenopausal Caucasian women.
Asunto(s)
Dieta , Evaluación Nutricional , Posmenopausia/fisiología , Vitamina K/administración & dosificación , Vitamina K/sangre , Ácido 1-Carboxiglutámico/orina , Adulto , Anciano , Sesgo , Estudios Transversales , Registros de Dieta , Ayuno , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores de TiempoAsunto(s)
Café/química , Té/química , Vitamina K 1/análisis , Cromatografía Líquida de Alta Presión , HumanosRESUMEN
Commercially available intravenous lipid emulsions are largely derived from vegetable oils, a natural source of phylloquinone (vitamin K1). We therefore examined the concentration of vitamin K1 in two widely used intravenous lipid emulsions by using a previously validated high performance liquid chromatography technique. The vitamin K1 concentrations of 10% emulsions of Intralipid and Liposyn II were 30.8 and 13.2 micrograms/dL, respectively. The concentration of vitamin K1 in the 20% emulsions of these products was essentially double that in the 10% emulsions. The coefficients of variation between the vitamin K1 content in three different lots of each product were consistently less than 7.0%. The observed concentrations of the vitamin in these lipid emulsions paralleled the predicted content on the basis of the type of vegetable oil(s) used to make the product. The type of vegetable oil used for production therefore seems to be a major determinant of the final vitamin K1 content. The vitamin K1 contained in these intravenous lipid emulsions is substantial and may have great impact on the vitamin K status of the recipient.
Asunto(s)
Emulsiones Grasas Intravenosas/química , Vitamina K 1/análisis , Cromatografía Líquida de Alta Presión , Emulsiones , Humanos , Fosfolípidos , Aceites de Plantas , Aceite de Cártamo , Aceite de SojaRESUMEN
We compared the intake of 12 micronutrients as reported on a semiquantitative food frequency questionnaire with corresponding biochemical indicators of nutrient status in a sample of 57 males and 82 females aged 40-83 y. Age-, sex-and energy-adjusted correlation coefficients ranged from near zero for thiamin, vitamin A, and zinc to 0.63 for folate. Correlation coefficients between intake and the biochemical measures were > 0.30 for carotenoids, vitamin D, vitamin E, vitamin B-12, folate, and vitamin C. Differences of 50% or more were observed between extreme quartiles of intake for mean plasma concentrations of folate, vitamin B-12, and vitamin C. Excluding nutrient supplement users generally reduced the correlations. These data demonstrate that food frequency questionnaires can provide valid information on intake for a number of micronutrients.
Asunto(s)
Registros de Dieta , Fenómenos Fisiológicos de la Nutrición , Encuestas y Cuestionarios , Oligoelementos/administración & dosificación , Vitaminas/administración & dosificación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Oligoelementos/sangre , Vitaminas/sangreRESUMEN
Although Freund's adjuvant has been used for decades as an immune enhancer in rabbits, adverse physiologic side effects have prompted the search for more suitable alternatives. We used osteocalcin, a bovine bone protein (M.W. 5,800), as the test antigen to evaluate four adjuvant regimens: a) primary inoculation with complete Freund's adjuvant (CFA) followed by three boosts with incomplete Freund's adjuvant (IFA), b) four serial inoculations with RIBI MPL+TDM+CWS adjuvant, c) four serial inoculations with TiterMax #R-1, and d) primary inoculation (only) with TiterMax #R-1. The antibody yield associated with the CFA/IFA regimen (mean OD = 2.152) was at least sixfold that of either TiterMax (mean OD = 0.358) or RIBI (mean OD = 0.239) multiple injection regimens. No antibody response was observed after the single injection of TiterMax antigen emulsion. Maximal antibody production occurred rapidly in response to Freund's adjuvant (day 31) as compared with TiterMax (day 74) and RIBI (day 66).