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Biomedical subjects

L S Hurley

Publications and source records attributed to L S Hurley.

At least 19 recordsLinked to original sources

Longitudinal changes in the mineral composition of mouse milk and the relationship to zinc metabolism of the suckling neonate.

We studied changes in the mineral composition of milk of lactating Swiss-Webster mice and the relationship of those changes to mineral metabolism of suckling mouse pups. Concentrations of Zn, Cu, Mg and Ca were analyzed in maternal and neonatal tissues and in milk; Zn metabolism was studied using 65Zn. Although Cu, Ca and Mg concentrations in milk declined during the first 2 d of lactation, only the concentration of Zn decreased progressively throughout 30 d. Various pup tissues were characterized by developmental changes in concentrations of some elements. Turnover of Zn in neonatal tissues was studied by radiolabeling litters in utero and fostering them at birth to nonradiolabeled lactating dams. The turnover of whole-body 65Zn in suckling mice decreased during development, and, at 20 d of age, the biological half-life of 65Zn in the neonate was approximately the same as for a nonpregnant, nonlactating adult female (20 d). The decreased turnover of 65Zn in lactating dams that characterized progressive lactation and was reflected in the Zn concentration of milk is in agreement with changes in whole-body 65Zn turnover observed for the suckling mouse. These findings demonstrate that the metabolism of the suckling neonate is directly related to longitudinal changes in the composition of maternal milk.

Animals

Mineral status of mice suckling early-, mid- and late-lactating foster dams.

We have demonstrated that the zinc (Zn) concentration of mouse milk declines significantly over the lactation period. Pups radiolabeled in utero with 65Zn were forward-fostered (FF) to nonradiolabeled dams at a later stage of lactation to study the effects of early milk deprivation. Other groups of radiolabeled pups were back-fostered at 5, 10 and 15 days of age to a nonradiolabeled dam who had just given birth; this provided additional colostrum during the suckling period. Litters fostered at birth to an unlabeled dam at d 0 of lactation were used as controls. Weight gain of FF litters decreased and signs of Zn deficiency increased as the foster dam's days of lactation increased. The Zn concentration of kidney, brain and plasma tended to decrease with increasing lactation days of the foster dam. Tibia Zn concentration declined progressively as the lactation days of the foster dam increased, and the concentration of calcium also was lower in all three groups of FF litters than in controls, indicating that bone calcification may have been impaired. Kinetic data proved to be a more sensitive index of Zn status than tissue Zn concentration. The biological half-life of whole-body 65Zn for FF suckling mice increased in a linear fashion with increasing lactation days of the foster dam; whole-body retention of 65Zn for back-fostered litters did not differ from that for controls. Brain, small intestine, kidney muscle, plasma and tibia of pups FF to late-lactating dams seemed to have greater retention of Zn than did controls. Thus, deprivation of early milk impaired growth and development of the mouse neonate despite some ability to conserve Zn.

Animals

Influence of maternal dietary zinc intake on in vitro tubulin polymerization in fetal rat brain.

The hypothesis that one of the biochemical lesions underlying zinc deficiency-induced teratogenicity is altered microtubule formation was tested. Day 19 fetuses from zinc-deficient Sprague-Dawley dams were characterized by low brain supernate zinc concentrations and slow brain tubulin polymerization rates compared to controls. Brain supernate tubulin and protein concentrations were similar in zinc-deficient and control fetuses. In vitro brain tubulin polymerization rates were increased following addition of zinc to either control or zinc-deficient brain supernates; however, the stimulatory effect of added zinc on polymerization was significantly higher in brain supernates obtained from zinc-deficient fetuses compared to controls. These results support the idea that one effect of fetal zinc deficiency is a reduction in tubulin polymerization, which in turn may result in altered microtubule function.

Animals

Effects of marginal zinc deficiency on microtubule polymerization in the developing rat brain.

One of the possible mechanisms that has been proposed to underlie the deleterious effects of zinc deficiency on brain development is an impairment in the normal formation of the cytoskeletal network. In the current study, in vivo microtubule polymerization was characterized in brain supernatant fluids, from 20-d-old pups whose dams were fed diets containing control (50 micrograms zinc/g) or marginal levels of zinc (10 micrograms zinc/g) throughout pregnancy and lactation. Pup brain and body weights were similar between the groups; however, plasma zinc concentrations were lower (27%) in pups fed the marginal zinc diet than in controls. Tubulin concentrations in 100,000 g brain supernates were similar between the groups; however, tubulin polymerization in the brain supernates was significantly lower in pups fed the marginal zinc diet compared to controls. Primarily, the early events of polymerization were affected; the lag period of the reaction was doubled, and the initial velocity was slower (26%) in supernates from pups fed the marginal zinc diet than in controls. These findings support the idea that some of the negative effects of marginal zinc deficiency on brain development and function may be mediated by an alteration in microtubule formation.

Animals

Effect of 6-mercaptopurine on 65Zn distribution in the pregnant rat.

The effect of 6-mercaptopurine (6-MP) on the distribution of gavaged 65Zn in maternal and embryonic tissues of Sprague-Dawley rats was examined 24 hr after injection of the drug on day 13 of pregnancy. 6-MP injection resulted in a significantly higher retention of counts of 65Zn in maternal liver and lower counts in maternal plasma, uterus, placenta, and embryo than in controls. Compared to controls, gel chromatography of maternal liver from 6-MP injected dams showed higher counts associated with a protein peak of molecular weight 6,000-8,000, the approximate molecular weight of the zinc-binding protein metallothionein. These results support the idea that the zinc deficiency, which is observed in day 21 fetuses from dams injected with 6-MP during midgestation, may be the result of a drug-induced sequestering of zinc into maternal liver followed by a decrease in maternal plasma zinc and subsequent reduction in fetal zinc uptake. We suggest that this 6-MP-associated redistribution of zinc into maternal liver may be due to induction of maternal metallothionein synthesis by the drug.

Animals

Effect of kainate-induced seizures on tissue trace element concentrations in the rat.

It has been shown that epileptics have lower mean blood concentration of manganese than do controls but the cause of this abnormality has not been determined. In order to investigate the effects of seizures on manganese distribution in the body, rats were treated with kainic acid to produce spontaneous seizures which were quantitated for number and severity. Manganese, zinc, copper and iron concentrations were determined in blood, brain, liver, heart and kidney. Kainate-treated animals ate more food but gained less weight than controls. Liver and kidney manganese concentrations were significantly higher in kainate-treated animals than in controls. Blood manganese concentration showed a significant negative correlation with seizure index while heart manganese concentration showed a significant positive correlation with seizure index. None of the other trace elements showed a significant correlation between trace element concentration and seizure index in any of the tissues, although iron concentration was lower in brain and copper concentration was lower in kidney of kainate-treated animals than in their appropriate controls. These data show that manganese concentrations are generally elevated in tissues of kainate-treated animals. This increased manganese concentration may be related to the increased energy demand of these animals.

Animals

The effect of valproic acid on 65Zn distribution in the pregnant rat.

The effect of valproic acid on the distribution of gavaged 65Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of 65Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher 65Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake.

Abnormalities, Drug-Induced

Effect of zinc or copper deficiency on erythrocyte purine nucleoside phosphorylase and pyruvate kinase activity in the rat.

The effect of deficiencies of zinc or copper in the rat on the activity of purine nucleoside phosphorylase and pyruvate kinase in erythrocytes, liver and muscle was investigated. The data showed no effect of either zinc or copper deficiencies on the activity of these enzymes in the tissues tested. It is concluded that these enzymes are not useful markers for either zinc or copper deficiency.

Animals

The effect of variable magnesium intake on potential factors influencing endurance capacity.

Rats fed a magnesium (Mg) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 micrograms/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.

Animals

Analysis of whole blood manganese by flameless atomic absorption spectrophotometry and its use as an indicator of manganese status in animals.

To investigate the use of whole blood manganese (Mn) as an indicator of total body Mn, we measured Mn in whole blood and liver of rats fed purified diets containing adequate (45 micrograms Mn/g diet) or deficient (1 microgram Mn/g diet) Mn. The mean hepatic Mn concentration was significantly lower (P less than 0.001) in the Mn-deficient group compared to the control group, 0.36, microgram Mn/g and 1.73 micrograms Mn/g, respectively. Furthermore, whole blood Mn was significantly reduced (P less than 0.001) in the deficient group when compared to the control group, 4.0 ng Mn/ml and 8.6 ng Mn/ml, respectively. Hepatic Mn linearly regressed against whole blood Mn yielded a statistically significant (P less than 0.001) correlation coefficient of 0.775. These data suggest that whole blood Mn is a valid indicator of body Mn status and thus may be useful, in addition to the measurements of serum copper and zinc, for the diagnosis and prognosis of diseases in which the metabolism of trace elements is affected. In addition, this paper describes and delineates operational parameters for the measurement of whole blood Mn using the IL 551 atomic absorption spectrophotometer and the IL 555 B flameless atomizer.

Animals

Copper deficiency-induced hypercholesterolemia: effects on HDL subfractions and hepatic lipoprotein receptor activity in the rat.

Male Sprague-Dawley rats (10 per group) were fed diets adequate (control) or deficient (CuDef) in copper for 6 wk. In the CuDef group, plasma total cholesterol, high density lipoprotein (HDL) cholesterol and apoA-I levels were significantly higher than in controls. Apolipoprotein analysis of the HDL fractions revealed a relative enrichment of apoE in the CuDef group. Size analysis of 1.21 density lipoproteins by nondenaturing gradient gel electrophoresis demonstrated the presence of more material migrating in the size range of HDL1 in the CuDef group. Separation of HDL into apoE-rich and apoA-I-rich fractions by heparin-affinity chromatography confirmed the presence of increased apoE-rich HDL in the CuDef group. To determine the mechanism responsible for higher apoE-rich HDL in the CuDef group, the lipoprotein receptor binding activity in hepatic membranes from the control and CuDef group was assayed. Kinetic analysis of the binding data revealed that the lipoprotein binding assay was primarily measuring the activity of the HDL receptor, which is not apoE mediated. When corrected for differential enrichment of plasma membrane, hepatic membranes from the CuDef group bound significantly fewer lipoproteins than did controls. Furthermore, the hepatic receptor binding activity was negatively correlated with the proportion of HDL enriched with apoE.

Animals

Evaluation of negative staining technique for determination of CN--insensitive superoxide dismutase activity.

The different forms of superoxide dismutase (superoxide-superoxide oxidoreductase, EC 1.15.11) have been studied, in tissues of rat, mouse and chicken, by the ectrophoresis-nitro blue tetrazolium technique proposed by Beauchamp. Similar enzyme patterns were evident in every tissue. A fast migrating CN--sensitive form of dismutase activity was present in isolated liver mitochondria of each species. Chicken and mouse liver mitochondria, as well as whole homogenate of every tissue of these two species, showed two additional slow-migrating bands of CN--insensitive activity. In contrast, such bands were not detectable in mitochondria isolated from rat liver or in any of the rat tissues analyzed by this technique. Prior to their electrophoretic separation, the samples were analyzed for CN--insensitive superoxide dismutase activity by a spectrophotometric assay; by this assay it was possible to demonstrate and quantitate a CN--insensitive superoxide dismutase activity in every preparation. Two units of CN--insensitive activity were applied to the gels for each sample. These results indicate that the electrophoresis-nitro blue tetrazolium technique is unsuitable for the detection of the rat CN--insensitive form of superoxide dismutase in crude preparations such as whole tissue homogenates or isolated mitochondria.

Animals

Developmental patterns of copper and zinc concentrations in mouse liver and brain: evidence that the gene crinkled (cr) is associated with an abnormality in copper metabolism.

An abnormality in copper metabolism during both the prenatal and postnatal (preweaning) periods was found to be associated with the autosomal recessive gene "crinkled" (cr) in mice. Liver copper concentration was significantly lower in crinkled mice (cr/cr) than in littermate controls (+/?) from 18 days of gestation to 20 days after birth. Crinkled mice older than 20 days of age and liver copper concentrations similar to those of littermate controls. Liver zinc and brain copper and were similar in crinkled and noncrinkled mice at all times tested. In both crinkled and noncrinkled mice, brain copper concentration increased during the suckling period, and liver copper concentration decreased.

Aging