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S Balderman

Publications and source records attributed to S Balderman.

7 recordsLinked to original sources

Metallothionein-induced increase in mitochondrial inner membrane permeability.

OBJECTIVE: To elucidate the effect of metallothionein on the permeability of the mitochondrial inner membrane. BACKGROUND: Metallothionein (MT) is a 6-7-kDa protein which is rapidly produced by stressed cells. MT is induced by cytokines and other factors thought to mediate the stress response. The organelle with the highest concentration of MT is the mitochondrion. Therefore we studied the effect of MT on mitochondrial function. We chose to study the effect of MT on mitochondrial inner membrane permeability because of the role of this function in numerous cellular processes. METHODS: Mitochondria were isolated from livers of Sprague-Dawley rats by differential centrifugation and suspended in sucrose-containing buffer. Changes in mitochondrial inner membrane permeability were monitored by following the change in absorbance at 540 nm. All experiments were of a paired design. RESULTS: We found that an increase in inner membrane permeability was induced by physiological metallothionein 1 (MT1) concentrations between 6 and 50 microM. There was no increase in the effect beyond 50 microM. The metals of MT1, zinc, and cadmium alone had no effect at physiological concentrations. The action of MT1 was inhibited by the aliphatic polyamine, spermine, as well as magnesium both at physiological concentrations. Spermine was effective whether added before or after MT1. Metallothionein 2 of different Zn2+ and Cd2+ compositions induced different kinetics of pore opening. CONCLUSIONS: These experiments reveal the possibility that the permeability of the mitochondrial inner membrane is regulated by relative concentrations of MT, spermine, and magnesium. The metal composition of MT could also play a role in this regulation.

Animals↗

Mitochondrial oxygen consumption is synergistically inhibited by metallothionein and calcium.

OBJECTIVE: To determine the combined effect of metallothionein and calcium on the oxygen consumption of mitochondria. BACKGROUND: We previously showed that mitochondrial oxygen consumption was inhibited by the intracellular acute-phase reactant, metallothionein, which is rapidly induced by nearly all stressed cells. Other investigators have demonstrated that calcium also inhibited oxygen consumption. However, the calcium concentrations used in their experiments were supraphysiologic. Our hypothesis was that metallothionein would enhance the effect of calcium. METHODS: We conducted these experiments, of a paired design, on the effects of combinations of metallothionein and calcium using mitochondria isolated from rat liver. An oxygen electrode implanted into a 600-microliter chamber with a stir bar was used to measure oxygen consumption. Various concentrations of calcium, metallothionein, and other reagents were added while oxygen consumption was being continuously recorded. Metals were removed from metallothionein by gel filtration to produce apometallothionein. RESULTS: Physiological levels of metallothionein synergistically enhanced the inhibitory effect of calcium so that its action occurred at physiological concentrations. Metallothionein devoid of its metals, zinc and cadmium, had no effect on oxygen consumption. CONCLUSION: In isolated mitochondria metallothionein inhibits ADP-initiated oxygen consumption. This effect is synergistic with the inhibitory action of calcium. These observations suggest a possible enhancement by metallothionein of the effect of fluxes in intracellular calcium in stressed cells.

Adenosine Diphosphate↗

Opposite effects of metallothionein I and spermine on mitochondrial function.

Previously, we reported that the stress-induced protein metallothionein I (MT) modulated the oxygen consumption (VO2) of isolated rat liver mitochondria [Life Sci. 55 221-226, 1994]. We now present confirmation of this finding, and the additional observations that in rat liver mitochondria, MT caused swelling and depolarization. These actions of MT were inhibited by the aliphatic polyamine, spermine. Our findings suggest that mitochondrial function could be influenced by the balance between MT and spermine.

Animals↗

Single-dose antimicrobial prophylaxis in open heart surgery.

A single one-gram pre-operative dose of ceftriaxone was compared with seven one-gram doses of cefazolin administered peri-operatively with the aim of preventing infections associated with coronary artery bypass graft surgery. Ninety-four evaluable cases were analyzed; 49 patients received ceftriaxone and 45 received cefazolin. There was no significant difference in the number of infectious complications between the two groups. Ceftriaxone had a terminal half-life of approximately 15.7 hours. There was no toxicity associated with either antibiotic. Because of the reduced number of doses, single-dose prophylaxis may result in considerable savings. Single-dose prophylaxis with ceftriaxone was found to be an effective modality for prevention of infection in open heart surgery.

Bacterial Infections↗

A comparison of the safety, efficacy, and distribution of ceforanide and cephalothin in coronary artery bypass graft surgery.

Antibiotic prophylaxis in open-heart operations is a widely accepted practice. Introduction of new antibiotics with differences in tissue distribution, spectrum of activity and therapeutic index prompts their evaluation as possible effective prophylactic agents. We compared the distribution, clinical efficacy, and safety of ceforanide with cephalothin as a prophylactic agent in coronary artery bypass graft (CABG) procedures. The results indicated that the intravenous administration of ceforanide at the dose of 1 gm every 12 hours for 2.5 days was equivalent to cephalothin 1 gm every 6 hours for 2.5 days. Serum, muscle, and bone concentrations of ceforanide were significantly greater than those of cephalothin. These concentrations consistently exceeded the minimal inhibitory concentration for Staphylococcus aureus, the major pathogen implicated in wound infections. No toxicty was observed with either antibiotic. Ceforanide merits consideration as a prophylactic antibiotic in CABG operations.

Aged↗