Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30-and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.The recommended dietary allowance (RDA) for vitamin C is 60 mg daily, based on threshold urinary excretion of the vitamin and on preventing the vitamin C deficiency disease scurvy with a margin of safety (1, 2).. Ingestion of 60 mg daily was proposed to prevent scurvy for 30-45 days if vitamin C intake ceased (1-7). Threshold urinary excretion of vitamin C was reported at the 60-mg daily dose (3,4,7,8 tTo whom reprint requests should be addressed.
A prospective cohort study was conducted to examine the effects of double-strength grapefruit juice on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics of terfenadine in poor metabolizers of terfenadine. Six healthy volunteers who were previously found to be poor metabolizers of terfenadine were studied, with each participant serving as his or her own control. In phase I of the study, terfenadine was given to participants at recommended dosages until steady state was achieved (60 mg twice daily for 7 days). In phase II, participants began receiving concomitant twice-daily, double-strength servings of grapefruit juice for 7 days. Serial pharmacokinetic and pharmacodynamic determinations were made after each phase of the study. The main outcome measures were serum concentrations of terfenadine and terfenadine acid metabolite, and corrected QT intervals as determined by 12-lead electrocardiogram. Significant changes occurred in time to maximum concentration (t(max)) and area under the concentration-time curve (AUC) of terfenadine and terfenadine acid metabolite after addition of grapefruit juice. All participants had detectable concentrations of unmetabolized terfenadine at the end of Phase I, which were quantified in three of the six participants. Further, all participants had increased and quantifiable levels of unmetabolized terfenadine after addition of grapefruit juice that were associated with prolongation of the QT interval relative to the baseline control period without terfenadine. Grapefruit juice did not alter the elimination half-life (t1/2) of terfenadine acid metabolite. Because of the intraindividual variability in the pharmacokinetics of terfenadine, further study is needed to confirm these results.
Цель исследования-оценка уровня цитокинов и активность системы комплемента в плазме крови и в смыве из десневого кармана у детей с хроническим генерализованным катаральным гингивитом в подросковом возрасте на фоне использования дополнительно к стандартному лечению геля пародонтоцида. Под постоянным наблюдением находилось 42 подростка в возрасте от 14 до 17 лет с верифицированным диагнозом: хронический катаральный генерализованный гингивит, которые были разделены на 2 группы: пациенты 1-й группы получали базисное лечение, а пациенты 2-й группы дополнительно в составе базисного лечения получали гель пародонтоцида. До начала лечения и через 2 недели определяли уровень фактора некроза опухолей альфа (TNFα), IL-2, IL-1α, IL-6, IL-18, интерферона-α (IFα), IL-8, IL-4, IL-10, рецепторного антагониста интерлейкина-1 (IL-1Ra), компонентов системы комплемента (С3, С3а, С4, С5, С5а, фактор H, С 1-ингибитора) и секреторного IgA. Применение только стандартного лечения у подростков с хроническим генерализованным катаральным гингивитом не оказывает необходимого иммунокорригирующего эффекта в отношении показателей системы комплемента и цитокинового звена иммунитета, а требует использования дополнительных средств фармакологической коррекции, в этом отношении эффективным является препарат «Пародонтоцид» в виде геля. Ключевые слова: хронический катаральный гингивит, препубертантный период, пародонтоцид, цитокины, система комплемента.
The effects of UV and magnetic radiation on the immunometabolic activity of ampicillin and cephazolin immobilized in erythrocytic and leukocytic carriers were studied in intact Wistar rats and animals infected with staphylococci. Erythrocytic and leukocytic carriers with antibiotics were obtained. Injection of free antibiotics stimulated the immunosuppressive, pro-oxidant, and hepatotoxic effects, associated with staphylococcal infection. Treatment with antibiotics in erythrocytic and leukocytic carriers stimulated (to different degrees) the activity of the immune system and stabilized the parameters of LPO, antioxidant defense, cytolysis, and cholestasis. Ultraviolet irradiation and magnetic field modified (to different measures) the immunometabolic effects of ampicillin and cephazolin, immobilized in erythrocytic and leukocytic carriers, in animals with staphylococcal infection.
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