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Biomedical subjects

B Fulton

Publications and source records attributed to B Fulton.

35 records · Page 2Linked to original sources

The temporal relationship between hepatic GSH loss, heme oxygenase induction, and cytochrome P450 loss following intraperitoneal aluminum administration to mice.

The time- and dose-dependent accumulation of aluminum (Al) in liver and its effect on several hepatic systems were investigated in female Swiss-Webster mice given intraperitoneal (ip) Al lactate. A single dose of 50, 75, or 100 mg Al/kg produced significant depletion of hepatic glutathione (GSH) and cytochrome P450 (P450) and an increase in heme oxygenase (HO) activity when measured at 6 hr. However, no increase in hepatic malondialdehyde (MDA) was seen at this time. Using a dose of 100 mg Al/kg, Al rapidly accumulated in liver (0.29 +/- 0.03 vs 0.12 +/- 0.04 micrograms Al/mg protein at 6 hr). Hepatic GSH was significantly depleted at 2, 4, and 6 hr postdosing, HO activity was significantly increased at 6, 12, 24, 48, and 96 hr postdosing, hepatic cytochrome P450 was decreased at 12, 18, 24, and 48 hr postdosing, while hepatic MDA was not significantly elevated until 24 hr postdosing. Twenty-four hours following three daily doses of 50 mg Al/kg, HO activity was increased, P450 levels were depleted, and hepatic Al content was significantly increased, although hepatic MDA was unaffected. We conclude that parenteral Al produces a course of hepatic damage that begins with GSH depletion and proceeds through a sustained increase in HO activity, with cytochrome P450 loss being an early event and production of hepatic MDA being a late event.

Aluminum↗

Heme oxygenase induction. A possible factor in aluminum-associated anemia.

The effect of repeated parenteral administration of aluminum (Al) was investigated to determine if a relationship exists between the severity of anemia and increase in hepatic heme oxygenase activity. Female Swiss Webster mice were dosed for 11 d with 50 mg Al/kg, as Al lactate, and sodium lactate was given to control mice. On d 12, hematocrit, hemoglobin, blood smears, hepatic heme oxygenase activity, and cytochrome P450 levels were assessed. Significant decreases in hematocrit (39.1 +/- 0.7 vs 43.1 +/- 0.3% in controls) and hemoglobin (13.1 +/- 0.4 vs 14.2 +/- 0.2 g/dL in controls) were produced by Al administration. Blood smears from Al-treated mice consistently showed smaller, more irregular red cells. Cytochrome P450 content was significantly decreased (0.443 +/- 0.043 vs 0.665 +/- 0.055 nmol/mg) whereas hepatic heme oxygenase activity was significantly increased (2.75 +/- 0.34 vs 1.66 +/- 0.20 nmol/mg/h) in Al-treated animals. The production of mild anemia by parenteral aluminum correlated significantly with the increase in heme oxygenase activity, which, although only 66% greater than in control, preceded a significant loss of cytochrome P450. The increased heme oxygenase activity, with subsequent increased destruction of heme and/or heme proteins is discussed as a possible mechanism for the microcytic, hypochromic anemia associated with Al overload.

Aluminum↗

Absorption and retention of aluminum from drinking water. 1. Effect of citric and ascorbic acids on aluminum tissue levels in rabbits.

Adult, male New Zealand rabbits (three per group) were administered drinking water containing aluminum chloride (0, 100, or 500 mg Al/liter) together with citrate (0.11 M), ascorbate (0.11 M), or no added ligand ad libitum for 12 weeks. They were fed ad libitum regular rabbit chow analyzed to contain 297 mg Al/kg. Treatment had no effect upon food and water intake or weight gain during the experimental period. No effect of aluminum was observed on tissue levels of the essential metals zinc, copper, and iron, or on hemoglobin and hematocrit values. Aluminum levels were found to increase in a dose-dependent manner in stomach and intestinal mucosa, kidney, bone, urine, and feces. There was only a slight accumulation in liver, and no accumulation in brain (cerebral cortex or hippocampus). Although plasma aluminum was directly related to aluminum intake, whole blood aluminum bore no relation to aluminum dose. Citrate had no effect on aluminum accumulation in the stomach or intestine, but significantly enhanced plasma and bone aluminum levels. Ascorbate did not enhance aluminum accumulation in any tissue studied and even prevented accumulation in bone. Both citrate and ascorbate enhanced excretion of aluminum. Ascorbate therapy may be of potential clinical use to enhance aluminum excretion.

Absorption↗

Bioavailability of aluminum from drinking water.

Aluminum, present in our drinking water as hydroxide or sulfate, is limited by solubility to 2.5 mg/liter at pH 7.0. This study was carried out to determine if aluminum at doses typically found in drinking water would accumulate in rat tissues if a ligand such as citrate at neutral or acid pH is coadministered, or in the absence of citrate at acid pH. Al(OH)3 or AlCl3 was given ad libitum in drinking water to male Sprague-Dawley rats at 0, 0.1, 2.0, or 100 mg/liter, in 4 mM acetate, pH 3.2 (A), 4 mM citrate, pH 2.6 (C), 4 mM citrate, pH 7.0 (7C), or distilled water, pH 7.0 (W). After 10 weeks, rats were killed and tissues were wet-ashed in nitric acid for determination of aluminum by flameless atomic absorption. Copper, iron, and zinc were determined by flame atomic absorption. Metal ion concentrations in tibia, brain, liver, blood, and kidney did not differ significantly between treatment groups. Aluminum accumulated in intestinal cells of all 100 mg Al/liter rats, with the C group accumulating more aluminum than the A or W groups. In the C group, intestinal aluminum content increased significantly in a dose-dependent manner. Intestinal iron was decreased significantly in all the 100 mg Al/liter groups. Intestinal copper was decreased in the W group at 100 mg Al/liter, with a trend toward a decrease in A and C groups. We conclude that at these low levels studied, aluminum accumulates in intestinal tissue, and that this accumulation is enhanced by citrate ligand. At 100 mg Al/liter, intestinal iron accumulation is decreased, and copper accumulation is marginally decreased.

Aluminum↗

Hydrogen peroxide as a source of molecular oxygen for in vitro mammalian CNS preparations.

Using an isolated neonatal rat spinal cord preparation, we have studied the ability of hydrogen peroxide to act as a source of oxygen for mammalian central nervous system (CNS) maintained in vitro. We report here that hydrogen peroxide, in low concentrations (0.001-0.004%), can effectively provide the only source, or act as a supplementary source of oxygen. This is brought about via the intracellular enzyme catalase which catalyzes the conversion of H2O2 into molecular oxygen and water.

Animals↗

A comparison of winged steel needles and Teflon cannulas in maintaining intravenous access during gastrointestinal endoscopy.

We have conducted a prospective study in 142 consecutive patients undergoing either gastroscopy or colonoscopy. The patients were randomized to have either a 23-gauge winged steel needle or a 23-gauge Teflon cannula inserted. The two groups were well matched, with 71 patients receiving each device. Intravenous access was achieved in every case. The steel needle was inserted at the first attempt in 65 of 71 cases (91.6%) compared with 67 of 71 cases (94.4%) for the Teflon cannula. Extravasation occurred in only 1 of 71 cases (1.4%) with Teflon cannulas compared with 18 of 71 cases (25.5%) of steel needle use (p < 0.01). Additionally, no Teflon cannula blocked completely, whereas 1 of 71 steel needles (1.4%) did so. Only 1 of 71 (1.4%) of the Teflon cannulas became difficult to flush compared with 12 of 71 steel needles (16.9%). The Teflon cannula was as easy to insert and provided significantly more reliable intravenous access than the steel needle.

Adult↗

Intravenous chlormethiazole.

Intravenous chlormethiazole is widely used for its sedative and anticonvulsant action in patients with acute alcohol withdrawal, status epilepticus, pre-eclampsia and eclampsia. Concern remains over its safety if it is given carelessly and without careful monitoring.

Chlormethiazole↗