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P W Fischer

Publications and source records attributed to P W Fischer.

At least 19 recordsLinked to original sources
PubMed1992

The relationship between the rate of chelator-induced zinc efflux from erythrocytes and zinc status.

The rate of zinc (Zn) release from rat erythrocytes incubated in buffers containing a variety of chelators was measured. Only o-phenanthroline, 8-hydroxyquinoline-5-sulfonate, and EDTA caused detectable Zn release. The relationship between the rate of this release in the presence of o-phenanthroline and Zn status was determined in rats. Rats were fed one of the following: a modified AIN-76 diet providing 46 mumol (3 mg) Zn per kg of diet, a pair-fed diet providing 459 mumol (30 mg)/kg, or the previous diet fed ad lib. Animals were sacrificed at 2-wk intervals for 12 wk, and the Zn efflux rate, plasma, liver, and femur Zn concentrations were determined. The efflux rate was lower in erythrocytes taken from the rats fed the low-Zn diet. The efflux rate was also well correlated with femur Zn (r = 0.509, n = 98, p < 0.0001). A poorer correlation was observed with plasma Zn in the rats. Correlations also were determined between efflux rates and plasma Zn levels in human subjects. There was a significant correlation only in the males. In was concluded that the Zn efflux rate from erythrocytes incubated in the presence of o-phenanthroline is related to Zn status but is not sensitive enough to be a useful index of this status.

Animals↗
PubMed1992

Indices of iron and copper status during experimentally induced, marginal zinc deficiency in humans.

This study examined the effect of diet-induced, marginal zinc deficiency for 7 wks in 15 men (aged 25.3 +/- 3.3 yrs; mean +/- SD) on selected indices of iron and copper status. The regimen involved low-zinc diets based on egg albumin and soy protein with added phytate and calcium such that mean [phytate]/[Zn] and [phytate] X [Ca]/[Zn] molar ratios were 209 and 4116, respectively, for 1 wk, followed by 70 and 2000, respectively, for 6 wks. Subjects were then repleted with 30 mg Zn/d for 2 wks. Plasma copper, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity in plasma and red blood cells (RBC), hemoglobin, hematocrit, and serum ferritin were determined weekly on fasting blood samples. Significant reductions (p less than 0.05) after 7 wks in RBC Cu,Zn-superoxide dismutase (49.5 +/- 7.2 vs 33.6 +/- 6.3 U/mg Hb) and serum ferritin (69.2 +/- 38.7 vs 53.8 +/- 33.7 micrograms/L) occurred; no comparable decline was noted for plasma Cu, hemoglobin, or hematocrit. Significant (p less than 0.05) but less consistent changes were also observed in plasma superoxide dismutase activity. None of the changes were associated with the decreases in plasma, urinary and hair zinc concentrations, and alkaline phosphatase activity in RBC membranes. Results indicate that the biochemical iron and copper status of the subjects was marginally impaired, probably from the dietary regimen that induced marginal zinc deficiency.

Adult↗
PubMed1991

Effects of low copper and high zinc intakes and related changes in Cu,Zn-superoxide dismutase activity on DMBA-induced mammary tumorigenesis.

The effect of low copper and high zinc intakes on Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity and mammary tumorigenesis induced by 9,10-dimethyl-1,2-benzanthracene (DMBA) was investigated. Groups of 40 weanling female Sprague-Dawley rats were fed a modified AIN-76 diet containing the following (/kg diet): 1 mg Cu (0.016 mmol) and 30 mg Zn (0.459 mmol); 6 mg Cu (0.094 mmol) and 30 mg Zn (0.459 mmol) (control); or 6 mg Cu (0.094 mmol) and 150 mg Zn (2.295 mmol) for 21 wk. At 5 wk, 30 rats/group were given 4 mg (15.6 mumol) DMBA in corn oil intragastrically, and controls (10/group) received corn oil alone. Erythrocyte Cu,Zn-SOD activity was measured at 3, 5 (just before DMBA), 9, 13, 17, and 21 wk. The group fed the high-Zn diet had a slightly lower weight gain and food consumption. DMBA treatment had no effect on these parameters. Plasma and liver Cu concentration decreased in the low-Cu group. Femur zinc was significantly elevated in the high-Zn group. Erythrocyte Cu,Zn-SOD activity was decreased in the low-Cu group from 3 to 21 wk and was significantly elevated in the high-Zn group at 3 and 5 wk. In the low-Cu group, there were 5 nonmalignant adenomas and 3 malignant adenocarcinomas; in the control group, there were 4 adenomas and 3 adenocarcinomas; in the high-Zn group, there were 5 adenomas and 3 adenocarcinomas. No relationship between Cu,Zn-SOD activity and the presence of tumors could be found.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

An evaluation of plasma and erythrocyte magnesium concentration and the activities of alkaline phosphatase and creatine kinase as indicators of magnesium status.

Rats were fed diets containing magnesium at concentrations ranging from 3.3 to 26.7 mmol/kg of diet (80 to 650 mg/kg). The magnesium concentration of their plasma and erythrocytes, and the activities of plasma alkaline phosphatase and creatine kinase were investigated to determine their usefulness as indices of magnesium status. All the indices increased with increasing dietary magnesium levels. The best correlations were observed between dietary intake and plasma concentration of magnesium (r = 0.846, p less than 0.001) and between intake and femur concentration (r = 0.811, p less than 0.001). There was an extremely high correlation between plasma concentration and femur concentration (r = 0.930, p less than 0.001). Although significant, the correlations between intake and the enzyme activities were not strong. It is concluded that plasma magnesium concentration is the most useful indicator of magnesium status and that the activities of the two magnesium-requiring enzymes can only be used for the purpose of diagnosing severely deficient magnesium status.

Alkaline Phosphatase↗
PubMed1989

Effect of dietary iodine on autoimmune thyroiditis in the BB Wistar rats.

Diabetes-prone BB Wistar rats were fed a modified AIN-76 diet providing the following amounts of iodine for 10 wk: 0.2 mg/kg diet (recommended amount); 1.0 mg/kg; 2.0 mg/kg; or 3.0 mg/kg. The thyroids were examined for gross and microscopic changes and sera were assayed for antibodies to triiodothyronine (T3), thyroxine (T4), and thyroglobulin (Tg). The body weights and food consumption of the rats fed 0.2 mg of iodine/kg were significantly lower than those of the animals fed higher amounts. Urinary iodine excretion reflected dietary intakes. The thyroids from animals fed 2.0 and 3.0 mg/kg were significantly (P less than 0.01) larger than those from animals fed 0.2 mg/kg. One rat fed 0.2 mg/kg and 2 rats in each group fed 2.0 and 3.0 mg/kg had extensive lymphocytic thyroiditis. Three rats fed 1.0 mg/kg, 6 fed 2.0 mg/kg and 6 fed 3.0 mg/kg had enlarged thyroids. Two rats fed 0.2 mg/kg, 2 fed 2.0 mg/kg and 6 fed 3.0 mg/kg had detectable Tg antibodies. These data suggest that high iodine intakes increase Tg antibodies, which may be associated with an increase in autoimmune thyroiditis in these animals.

Animals↗
PubMed1989

Effects of dietary selenium on DMBA-induced carcinogenesis in rats fed a diet high in mixed fats.

The effects of selenium intake on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis were examined in rats fed a diet high in mixed fats and representative of that consumed in North America. Six groups of 20 rats were fed an AIN-76 diet modified to contain 20% fat from lard:corn oil (3:1 wt/wt) and various amounts of selenium (0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet). At wk 5, animals in groups 2-6 were dosed with 4.32 mg of DMBA. Serum clinical parameters and the activities of plasma selenium-dependent and total glutathione peroxidase (GSHPx), erythrocyte GSHPx and superoxide dismutase (SOD) were determined every 4 wk for 25 wk. The extent of lipid peroxidation was determined by measuring urinary malondialdehyde during wk 13 and 24, and erythrocyte malondialdehyde at wk 25. Erythrocyte GSHPx was found to be a better indicator of selenium status than plasma activity, while SOD did not vary with dietary selenium. The group of animals fed 4.0 mg Se/kg diet had reduced numbers of tumors (P less than 0.01), but this reduction was associated with evidence of chronic selenium toxicity. Variations in GSHPx activity with dietary selenium did not result in differences in tumor incidence, nor in changes in lipid peroxidation in the other groups. Thus, nontoxic levels of selenium do not appear to offer any protective effect during carcinogenesis in rats fed a casein-based diet similar in fat content to that consumed by North Americans.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Changes in selenium and antioxidant status during DMBA-induced mammary carcinogenesis in rats.

Female weanling Sprague-Dawley rats were used to examine the changes that occurred in selenium and antioxidant status during the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. Animals were fed an AIN-76 diet, modified to contain 20% fat (3:1 wt/wt, lard:corn oil) and 0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet. At wk 5, rats in groups 2-6 were administered by intragastric tube 4.32 mg of DMBA dissolved in corn oil. Control rats received corn oil only. A blood sample was removed from the tail vein and analyzed for selenium-dependent glutathione peroxidase (Se-GSHPx) and superoxide dismutase (SOD) activity at wk 5, and every 4 wk until wk 25. At the end of the experiment, rats were classified by tumor status, and each diet group was subdivided into two groups: those rats remaining free of tumors for 25 wk and those with tumors. DMBA treatment caused an initial decrease in erythrocyte SeGSHPx and SOD activity compared to untreated control rats. SeGSHPx activity in rats with tumors remained lower than controls, while SeGSHPX activity increased in rats with no tumors. These changes, however, were not associated with any changes in lipid peroxidation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Effects of dietary magnesium on sodium-potassium pump action in the heart of rats.

Sprague-Dawley rats were fed a basal AIN-76 diet containing 80, 200, 350, 500 or 650 mg of magnesium per kilogram of diet for 6 wk. Ventricular slices, as well as microsomal fractions, were prepared from the hearts and were used to determine sodium-potassium pump activity. Sodium-potassium pump activity was assessed in the microsomal membranes by determining the ouabain-inhibitable Na+, K+-ATPase activity and [3H]ouabain binding, and in the ventricular slices, by determining ouabain-sensitive 86Rb uptake under K+-free conditions. The ATPase activity increased with increasing dietary magnesium, so that in the hearts of those animals that were fed 500 and 650 mg of magnesium/kg diet, it was significantly greater than the activity in the hearts of the animals fed 80 and 200 mg/kg diet. Similarly, 86Rb uptake by heart slices from rats fed 500 and 650 mg of magnesium/kg diet was significantly greater than the uptake by heart slices from animals fed 80 and 200 mg/kg diet. [3H]Ouabain binding did not change with increasing dietary magnesium. Thus, magnesium deficiency appears to have no effect on the number of sodium-potassium pump sites, but does decrease the activity of the pump. It is suggested that this leads to an increase in intracellular Na+, resulting in a change in the membrane potential, and may contribute to the arrhythmias associated with magnesium deficiency.

Animals↗
PubMed1986

An automated method for the determination of Cu,Zn-superoxide dismutase in plasma and erythrocytes using an ABA-200 discrete analyzer.

An automated enzymatic method is described for the determination of Cu,Zn-superoxide dismutase (SOD) in plasma or erythrocytes using the xanthine-xanthine oxidase and cytochrome C coupled assay. This method was adapted to an Abbott ABA-200 discrete analyzer. Coefficients of variation for within-run and day-to-day analyses were less than 5%. Only 2.5 muL of serum or erythrocyte extract is required so a capillary tube sample of blood (70 muL) is sufficient for the assay. Recovery of added SOD ranged from 92 to 101%. The method reported here is practical for use in a clinical chemistry laboratory for monitoring changes in this enzyme, which is a sensitive early indicator of alterations in copper status.

Animals↗
PubMed1979

Hormonal effects on the regulation of hepatic heme biosynthesis.

Drug-induced porphyrin accumulation occurs in chick embryo liver cells maintained in serum-free Waymouth MD 705/1 medium. Addition of insulin and thyroxine to the medium results in a marked enhancement of porphyrin accumulation. The addition of hydrocortisone results in a further enhancement of porphyrine accumulation. Several agents which are reported to increase intracellular adenosine 3':5'-monophosphate (cAMP) levels, viz. glucagon, sodium fluoride, cAMP or its dibutyryl derivative, 3-isobutyl-1-methylxanthine and papaverine enhanced drug-induced porphyrin biosynthesis. On the other have, agents which are reported to decrease intra-cellular cAMP levels, viz. alloxan and imidazole, diminished drug-induced porphyrin accumulation. cAMP appears to enhance, but not to function as a "second messenger" in drug-induced porphyrin biosynthesis. Drug-induced porphyrin accumulation in chick embryo liver cells depend upon the insulin to glucagon ratio. A low level of porphyrin accumulation occurs at insulin to glucagon ratios similar to those found following glucose administration in vivo, suggesting a possible explanation for the therapeutic effect of glucose in hepatic porphyria. The 5 alpha A(A:B trans) and 5 beta H(A:Bcis) steroids are equipotent in inducing delta-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus, there is no specific steric requirement for porphyrin-inducing activity in steroids.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Porphyrin-inducing activity of alfaxolone and alfadolone acetate in chick embryo liver cells.

The two steroid components of Alfathesin, alfaxolone and alfadolone acetate, have been tested for porphyrin-inducing activity in chick embryo liver cell culture and for hepatic ALA-synthetase-inducing activity in the 17-day-old chick embryo. In cell culture alfoxolone was shown to have potency comparable to that of thiopental, while alfadolone acetate had low potency. In the 17-day-old chick embryo alfaxolone has a third the potency of thiopental; alfadolone acetate showed low potency. The authors conclude that an induction dose of Alfathesin would be less likely than a comparable dose of thiopental to increase ALA-synthetase activity in a patient with hereditary hepatic porphyria.

Alfaxalone Alfadolone Mixture↗