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The relative toxicity of low doses of lead acetate provided steadily in drinking water or by mouth once per week was studied in weanling and adult rats. Free erythrocyte protoporphyrin and urinary delta-aminolevulinic acid levels were measured, as well as lead levels in blood and kidney. The accumulation of lead in brain tissue and in bone (femur) was measured to determine the effect of age and schedule of administration on tissue distribution and retention of lead. Total intakes of lead during the 60-week experimental period were: weanling and adult rats exposed to drinking water supplemented with 200 microgram of lead acetate/ml: 127 +/- 10 mg and 160 +/- 16 mg, respectively; weanling and adult rats dosed with lead acetate orally once per week: 132 mg and 161 mg, respectively. Increased toxic effects of lead in the weanling animals were apparent in most of the parameters measured (urinary delta-aminolevulinic acid and blood, brain, femur and kidney lead levels). This pattern was observed in weanling rats exposed to lead steadily through drinking water or dosed orally with an equivalent quantity of lead once per week. Lead levels in blood were highly correlated with the accumulation of lead in brain, femur, and kidney tissue in both groups of weanling rats. In adult rats, significant correlations between blood lead and kidney lead and between blood lead and femur lead were found only in the rats receiving lead steadily in drinking water.

The initial nutritional status of experimental animals can influence their response to subsequent dietary regimens. In the present study, we determined the variations in minerals in diet NIH-31, a breeding colony stock diet, and in tissues of weanling rats nursed by dams fed this diet. Inductively coupled plasma-atomic emission spectrometry (ICP-AES) was used to determine nine elements (Ca, Cu, Fe, K, Mg, Mn, Na, P and Zn) in diet and in liver, kidney, spleen, duodenum and femur from 22- to 26-day-old rats. Wet digestions were performed in mixtures of nitric, perchloric, and sulfuric acids (diets and soft tissues) or nitric and perchloric acids (femur). Solution concentrations ranged from less than 25 ng/ml for the trace elements to greater than 100 micrograms/ml for the major elements. Large variations in mineral content were found between batches of commercially prepared NIH-31 diet; relative amounts of Cu, Fe, Mn and Zn varied markedly. Significant differences in concentrations of major and trace minerals in liver, kidney, spleen and duodenal tissue were found among groups of weanling rats obtained from the same supplier at different times. Mn was readily quantitated in all tissues except spleen, where it was below detection limits. The precision obtained with the ICP-AES methodology has significant advantages for establishing variations in tissue mineral levels.

Resistance to the antifolates methasquin and amethopterin has been studied in new strains of Streptococcus faecium var. durans . Two methasquin-resistant strains (SF/MQ, SF/MQ T ) and an amethopterin-resistant strain (SF/AM) were selected independently from the wild-type S. faecium var. durans (SF/O). SF/MQ T is a thymine auxotroph. Total dihydrofolate reductase activity was elevated in each of the resistant strains. The greatest increase (36-fold) was observed in extracts of SF/AM. The methasquin-resistant strains, SF/MQ and SF/MQ T , had 29-fold and 8-fold, respectively, more dihydrofolate reductase activity than the parental strain. Total dihydrofolate reductase activity of SF/O was separable by gel filtration into two components: a folate reductase (11%) and a specific dihydrofolate reductase (89%). Folate reductase activity was associated with 88% of the total dihydrofolate reductase activity of SF/MQ T , with specific dihydrofolate reductase activity accounting for the remaining 12%. In SF/MQ and SF/AM, folate reductase activity was associated with 97% of the total dihydrofolate reductase activity. Studies of the inhibition by methasquin and amethopterin of partially purified folate reductase and specific dihydrofolate reductase of the mutant strains suggested that resistance was not accompanied by changes in the affinities of these enzymes for either antifolate.

The relative toxicity of lead acetate provided at uniform dosages (mg/kg body weight/week) in drinking water or by a single weekly po administration was studied in weanling and adult Sprague-Dawley rats. Free erythrocyte protoporphyrins, urinary δ-aminolevulinic acid, and lead levels in blood, brain, kidney, and femur were measured. Effects of age and schedule of administration were evaluated by calculating the percentage of ingested lead retained in brain, kidney, and femur. No effects of age on levels of lead in blood or in brain tissue were observed within the same dosage schedule group when dosing was equivalent on the basis of body weight. Weanling rats had lower levels of lead in kidney and higher levels in femur than did equivalently dosed adult rats. Concentrations of lead in blood, kidney, and femur were significantly higher in weanling rats exposed to lead daily in drinking water than in weanling animals receiving an equivalent dose of lead once per week. Brain lead levels were significantly higher in adult rats receiving lead in drinking water than in intermittently exposed adult animals. Weanling rats retained significantly higher fractions of ingested lead in brain tissue and in femur than did equivalently dosed adult rats under both schedules of lead administration. Under conditions of intermittent exposure to equivalent doses of lead, adult rats retained a higher percentage of lead in kidney tissue than did weanling animals. Lead retention in kidney tissue of weanling rats was significantly higher when lead was provided daily than when equivalent doses were administered at weekly intervals.

Standardized purified diets limited to required nutrients are needed for nutritional and toxicological studies. In the present study, we formulated a biotin- and cellulose-free diet of reproducible mineral composition (diet A), based on diet AIN-76, and fed it to weanling Long-Evans rats for 3 wk. Inductively coupled argon plasma atomic emission spectrometry was used to determine Ca, Cu, Fe, K, Mg, Mn, Na, P and Zn in liver, duodenum, kidney, spleen and femur. Results were compared with those obtained with rats fed biotin- and/or cellulose-supplemented variations of diet A, diet AIN-76 and diet NIH-31 (an open-formula stock diet). Weanling rats grew slowly and steadily on purified diet A. Growth rates increased when diet A was supplemented with biotin and cellulose. In general, differences among tissue mineral levels in rats fed diet NIH-31 and those fed diet AIN-76 were more pronounced than those among groups fed our purified diets. Values for hemoglobin and hematocrit were significantly lower in rats fed all purified diets than in those fed diet NIH-31. Diets A + biotin, A + cellulose and A + cellulose + biotin appear satisfactory as reference diets for measuring mineral interactions at near-requirement levels as well as effects of fiber on mineral utilization or for studies on vitamins whose endogenous synthesis may be influenced by dietary fiber.

Lead is an ubiquitous contaminant of food and water supplies. Under some circumstances, this contamination can be quite severe, as described in case reports of clinical lead poisoning in which food or water was the source of lead. It is not clear at present if lead is more toxic when added to food or to water because literature relating to this specific problem is limited. Because of the general effects of food intake on reduction of lead absorption in humans, it is possible that lead-contaminated water is more toxic than lead-contaminated food. The purpose of this study was to determine if equal concentrations of lead acetate added to food or to water were equally bioavailable to rats.

[ 14 C ]- N -ethylmaleimide has been used to label binding sites for methotrexate in the plasma membranes of L 1210 cells previously ‘protected’ from reaction with unlabeled N -ethylmaleimide by the presence of methotrexate. A [ 14 C ]- N -ethylmaleimide labeled protein of molecular weight 56,000 was subsequently identified by electrophoresis of crude plasma membranes in sodium dodecyl sulfate containing polyacrylamide gels. Sepharose—methotrexate affinity chromatography was used to isolate an active methotrexate binding protein fraction from L 1210 lymphoma cell plasma membranes. This protein fraction was isolated from crude plasma membrane preparations and from a detergent extract of intact cells. The latter method carried out in the presence of 0.01% TritonX- 100 permits the rapid extraction of plasma membrane proteins from intact L 1210 cells in the absence of extensive cellular destruction. The methotrexate binding capacity of the extracted protein material has been demonstrated. The protein fraction purified by affinity chromatography contains 3 major protein components of molecular weights 67,000, 63,000 and 56,000 as determined by sodium dodecyl sulfate gel electrophoresis.

Serial serum zinc concentrations were measured in 31 relatively well, growing premature infants during the first 26 weeks of life. Zinc concentrations declined progressively from 17.9 mumol (1.17 mg/l) at birth (normal adult value) to 8.9 mumol (0.58 mg/l) at 6 weeks of age despite a zinc intake of greater than 13.7 mumol (900 micrograms)/kg/day after the second week of life. The serum zinc increased after 16 weeks of age to 10.7 mumol/dl (0.7 mg/l). No infant demonstrated clinical signs of zinc deficiency. This data may serve as a reference against which serum zinc concentrations in other premature infants may be compared in order to help define the deficiency state.

In order to define the range of serum copper concentrations in preterm infants and to determine the effect of growth upon these values, serial serum copper concentrations were measured in 26 preterm infants over their first six weeks of life. Fourteen healthy, growing preterm infants (Group I) had mean serum copper concentrations below 32 microgram/dl throughout the study. Clinical and hematologic signs of copper deficiency which responded promptly to the oral administration of copper sulfate were noted in five of these 14 infants. Twelve ill preterm infants (Group II-A), who received parenteral nutrition without supplemental copper and had slow rates of growth, had mean serum copper concentrations above 50 micrograms/dl after the first week of life. Seven surviving from Group II-A (Group II-B) had a decrease in mean serum copper concentrations to values similar to those in Group I after two weeks of oral feedings and resumption of normal growth. Our findings suggest that preterm infants who have normal growth while receiving oral feedings are at significant risk for developing copper deficiency.

Publisher Summary At the oxidation states of formate, formaldehyde, and methanol, the enzyme reactions occur as steps in the metabolic production or breaking down of purines, pyrimidines, and amino acids. These transfer reactions are mediated by the coenzyme form of folic acid, tetrahydrofolate, whose structural features allow it to form adducts with the one-carbon groups by covalent linkages at N -5 and N -10. This property provides the basis for the ability of the coenzyme to accept and donate one-carbon groups from metabolites. This chapter describes all of the enzymes responsible for these reactions, with the exception of the B 12 -dependent 5-methyltetrahydrofolate-homocysteine transmethylase and methylenetetrahydrofolate dehydro-genase and methylenetetrahydrofolate reductase, both of which catalyze reactions involving oxidoreduction rather than the transfer of the one-carbon group. The chapter discusses the transfer of fomate and its congeners, including 10-formyltetrahyderofolate synthetase, 10-formyltetrahydrofolate decyclase, 5-formyltetrahydrofolate cyclodehydrase, 5,10-methenyltetrahydrofolate cyclohydrolase, glycinamide ribonucleotide transformylase, formiminoglycine formiminotransferase, formiminoglutamate formiminotransferase, N -formylglutamate transformylase, and methionyl-transfer RNA transformylase. The deacylation of 10-formyltetrahydrofolate proceeds through a formyl intermediate that is oxidized before being released as CO 2 . These results also help to explain why CO 2 production from formate is depressed when animals are maintained on a folate-deficient diet. ATP-supplemented pigeon liver extracts utilizes 5-formyltetrahydrofolate (folinic acid) in the conversion of the purine precursor, 5-amino-4-imidazole carboxamide-5′-phosphoribotide, to inosine-5’-phosphate. Both the transformylase and inosinicase have been partially purified from chicken liver. The transformylase, but not inosinicase, is markedly stimulated by K + . The existence of two separate enzymes is suggested by the K + dependence of only the transformylase. The degradation of histidine in Pseudomonas fluorescens , Aerobacter aerogenes , and mammalian liver leads to the formation of N-formimino-L-glutamate. In liver, the formimino group is transferred to tetrahydrofolate.

Following the severe malaria outbreak in the central highlands in Madagascar in 1986, a vector control program by use DDT pm 75 house-spraying has been implemented to operate in areas located at altitudes between 1000 and 1500 m. Early treatment with chloroquine has also been incorporated in the control program. To detect areas at particular high risk for malaria outbreak the Geographic Information System (GIS) has been applied and tested. The study has shown that the system can be used in malaria surveillance in order to identify areas in which an intense distribution of Anopheles funestus can be anticipated and, hence, targeted in spraying campaigns. The system may also be used to monitor changes in anti-malarial drug resistance, in addition, to control of other vector-born diseases.