Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory.

Cognitive and memory deficits can be caused or exacerbated by dietary folate deficiency, which has been combatted by the addition of folate to grains and dietary supplements. The recommended dose of the B9 vitamin folate is 400 µg/day for adolescents and non-pregnant adults, and consumption above the recommended daily allowance is not considered to be detrimental. However, the effects of excess folate have not been tested in adolescence when neuro and endocrine development suggest possible vulnerability to long-term cognitive effects. We administered folate-supplemented (8.0 mg folic acid/kg diet) or control lab chow (2.7 mg folic acid/kg diet) to rats ad libitum from 30 to 60 days of age, and subsequently tested their motivation and learning and memory in the Morris water maze. We found that folate-supplemented animals had deficits in motivation and spatial memory, but they showed no changes of the learning- and memory-related molecules growth-associated protein-43 or Gs-α subunit protein in the hippocampus. They had decreased levels of thyroxine (T4) and triiodothyronine (T3) in the periphery and decreased protein levels of thyroid receptor-α1 and -α2 (TRα1 and TRα2) in the hippocampus. The latter may have been due to an observed increase of cytosine-phosphate-guanosine island methylation within the putative thyroid hormone receptor-α promoter, which we have mapped for the first time in the rat. Overall, folate supplementation in adolescence led to motivational and spatial memory deficits that may have been mediated by suppressed thyroid hormone function in the periphery and hippocampus.

Nonparametric approach to population pharmacokinetics in oncology patients receiving aminoglycoside therapy.

A nonparametric expectation maximization approach to the study of population pharmacokinetics is described for an aminoglycoside antibiotic. The method is used to explore population estimates for gentamicin clearance (liters per hour per creatinine clearance) and volume of distribution (liters per kilogram) in tumor patients. Joint and marginal probability distributions are plotted and further characterized by using standard descriptors such as mean, median, mode, standard deviation, skewness, and kurtosis. Results of additional analyses using hematologic or solid tumor subpopulations agree with those of a recent larger study which found no significant pharmacokinetic differences between these groups. Nonparametric maximum-expectation analyses are convenient and allow exploratory analysis of population estimates directly from routine laboratory information.

The perinatal impact of cocaine, amphetamine, and opiate use detected by universal intrapartum screening.

Universal urine testing for cocaine, amphetamines, and opiates was performed on 1643 women admitted to an obstetric service for a 1-year period with 20.5% having positive results. There were 299 patients with positive toxicology results matched for race and discharge date with patients having negative toxicology and drug history. Significant differences in age, prior obstetric history, prenatal care, alcohol history, and smoking were noted between groups. There was a significant decrease in birth weight, head circumference, length, and gestational age for the drug-positive group, which was most marked in cocaine and multiple drug users. These differences persisted after we controlled for smoking, prenatal care, and prior preterm births. Differences in birth weight and head circumference remained after we controlled for gestational age. Rates of congenital anomalies and abruptio placental were similar between groups. Perinatal substance abuse is independently associated with growth retardation and prematurity. Multiple risk factors are frequently present, necessitating a comprehensive approach to prenatal care.

Folic acid compounds in romaine lettuce.

The composition of folate coenzymes in romaine lettuce was studied. Lettuce extract was purified on QAE-Sephadex A-25 and folate compounds were separated into a monoglutamate fraction and a polyglutamate fraction by chromatography on Sephadex G-15. Both the mono- and poly-glutamate fractions were resolved on DEAE-cellulose. Positive identification of DEAE peaks was made by further cochromatography with high specific activity radioactive marker folate compounds and with differential microbiological assay. The distribution of folate compounds in lettuce is as follows: 32% 5-CH3-H4PteGlu; 1% 5-CHO-H4PteGlu; 3% 5-CHO-H4PteGlu4; 9% 5-CH3-H4PteGlu4; 13% 5-CHO-H4PteGlu5; and 31% 5-CH3-H4PteGlu5.

Determination of linkages in beta-D-Glucans from Phaseolus aureus by exo-beta-(1 to 3)-D-glucanase.

An alkali-insoluble glucan synthesized from UDP-d-glucose by the particulate enzyme system from Phaseolus aureus is hydrolyzed by a highly purified exo-beta-(1 --> 3)-d-glucanase to d-glucose, to the extent of 91% in 24 hr. The alkali-insoluble glucan from GDP-d-glucose formed by the particulate enzyme system from the same plant which is known to be (from chemical data) a beta-(1 --> 4)-d-glucan (cellulose) is not acted upon by this glucanase.

Biosynthesis of Insoluble Glucans From Uridine-Diphosphate-d-Glucose With Enzyme Preparations From Phaseolus aureus and Lupinus albus.

Particulate, and digitonin-solubilized, enzyme systems from Phaseolus aureus and Lupinus albus catalyze the biosynthesis of aqueous-insoluble glucans from UDP-d-glucose. The digitonin treatment greatly increases the enzymic activity of (per unit protein) both the 34,000g pellet and the supernatant liquid as compared with that of the original particles. Most of the polymer produced (90-95%) is soluble in hot, dilute alkali; the interglucosidic linkages of the alkali-soluble and alkali-insoluble polymers are identical. The optimum concentration for the incorporation of radioactivity from UDP-d-glucose-(14)C into soluble glucan is high; at 10(-3)m at least 50% of the added radioactive glucosyl donor is incorporated.Careful examination of the products of degradation of the polymers produced by various enzymic preparations showed that beta-(1-->3)-glucans are produced. No evidence was obtained for any measurable amount of beta-(1-->4)-d-glucose linkages.