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16 recordsLinked to original sources
PubMed1992

Wilson's disease treatment by triethylene tetramine dihydrochloride (trientine, 2HCl): long-term observations.

Wilson's disease is an autosomal recessive disorder characterized by an accumulation of a toxic amount of copper in the body. Triethylene tetramine dihydrochloride (trientine, 2HCl) is a new chelating agent that may be effective in the removal of excess copper but long-term efficacy has not yet been investigated. Here we report the use of trientine over more than 8 years in 2 patients with Wilson's disease who could not tolerate D-penicillamine. We found no significant side effect, except a decreased serum iron concentration without clinical symptoms of anemia. In annual examinations at a steady state, the serum copper levels remained below 20 micrograms/100 ml. The 24-hour urinary copper excretion was less than that found using D-penicillamine, while the basal copper excretion, after 5 days abstinence from trientine, was maintained below 100 micrograms/day. Both hepatic and neurological manifestations except bulbar symptoms were recovered without any initial deterioration.

Adolescent↗
PubMed1992

Effects of an inhibitor and a mimic of superoxide dismutase on bleomycin mutagenesis in Chinese hamster ovary cells.

We have investigated the roles of reactive oxygen species (ROS) in bleomycin (BLM)-induced gene mutations in Chinese hamster ovary (CHO) cells using a superoxide dismutase (SOD) inhibitor, triethylenetetramine (TRIEN), and a SOD mimic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEM-POL), to lower and increase intracellular 'SOD activity', respectively. Pretreatment of CHO cells with TRIEN (1 mM) for 1 h enhanced the mutagenic response of BLM (5-50 micrograms/ml, 1 h treatment) in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in CHO cell clone K1-BH4 (CHO/HPRT assay) and the xanthine-guanine phosphoribosyltransferase (gpt) gene in a CHO-K1 cell derivative AS52 (AS52/GPT assay). Pretreatment with TEMPOL (1 mM) for 1 h decreased the BLM (20-100 micrograms/ml, 1 h treatment) mutagenicity in the AS52/GPT assay. The mutagenic response of BLM appears to be modulated by the intracellular level of 'SOD activity' and hence the intracellular level of ROS. These data provide further evidence for the involvement of ROS in bleomycin mutagenesis in mammalian cells.

Animals↗
PubMed1977

The effect of certain chelating compounds on the urinary excretion of copper by the rat: observations on their clinical significance.

1. A screening procedure is described to assess rapidly the clinical potential of chelating agents for the treatment of Wilson's disease. 2. Rats were used as the test animal; they were kept in metabolic cages and the urine was collected in copper-free containers. The compounds investigated were given by mouth as a standard dose of 100 mg. Copper was determined by atomic absorption spectrophotometry. 3. Basal urine copper excretion was 65-1 +/- SE 2-93 nmol/24 h (4-1 microgram +/- 0-185). After penicillamine this rose to 367-1 nmol and after trien to 305-9 nmol. 4. Certain compounds caused a reduction in the amount of copper excreted in the urine, probably by forming insoluble chelates with the metal, hence rendering it unavailable for excretion at the glomerulus.

Animals↗
PubMed1976

Cross-reactions between ethylenediamine, diethylenetriamine and triethylenetetramine.

A consecutive series of 1544 patients and 137 patients in occupational contact with epoxy resins were tested with ethylenediamine and/or triethylenetetramine; some were tested with diethylenetriamine. Guinea pigs sensitized to triethylenetetramine were tested with ethylenediamine and diethylenetriamine. The results showed that cross-reactions may occur between triethylenetetramine and ethylenediamine, although the majority of the patients were sensitized to only one of the compounds.

Allergens↗
PubMed1978

Effect of triethylenetetramine dihydrochloride on the antibiotic susceptibility of Pseudomonas aeruginosa.

A chelating agent, triethylenetetramine dihydrochloride, interacted synergistically in vitro with both gentamicin and carbenicillin against a clinical isolate of Pseudomonas aeruginosa designated Ps 15. The minimal inhibitory concentrations of carbenicillin and gentamicin for Ps 15 in a 50% serum-Trypticase soy broth were 250 and 72.9 mug/ml, respectively. However, addition of triethylenetetramine dihydrochloride to the 50% serum-Trypticase soy broth reduced the minimal inhibitory concentration of both antibiotics approximately 10-fold. A comparison of the growth of Ps 15 in 50% serum-Trypticase soy broth containing either of the antibiotics showed that a rapid decrease in the percentage of survivors only occurred when the chelating agent was present.

Anti-Bacterial Agents↗
PubMed1992

Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse.

The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse.

Animals↗
PubMed1979

The effect of triethylenetetramine dihydrochloride on the in vivo susceptibility of Pseudomonas aeruginosa to gentamicin.

A chelating agent, triethylenetetramine dihydrochloride (TRIEN dihydrochloride) increased the efficacy of gentamicin in vivo against a clinical isolate of P. aeruginosa, designated Ps 15. Mice which were inoculated with 10 X LD50 of Ps 15 and treated with doses of 2 approximately 16 mg of gentamicin per kg per day all died. However, treatment with 8 mg of gentamicin per kg body weight per day plus 30 mg of Trien dihydrochloride per day markedly reduced the mortality. The combined therapy also reduced the number of viable organisms that accumulated in the kidney during a 24-hour period post inoculation. When a dosage level of 8 mg of gentamicin was exceeded in the combined treatment regimen, all of the infected mice died, and a high concentration of endotoxin could be detected in the mouse sera by the limulus assay.

Animals↗
PubMed1977

Comparisons of antidotal efficacy of sodium diethyldithiocarbamate, D-penicillamine and triethylenetetramine upon acute toxicity of nickel carbonyl in rats.

Sodium diethyldithiocarbamate, D-penicillamine, and triethylene-tetramine were administered to rats by im injection in dosages equivalent to 0.6 times their respective LD50 values in order to compare their relative effectiveness in prevention of death caused by exposure for 15 min to inhalation of nickel carbonyl (1.4 or 4.2 mg Ni (CO)4/liter of air). When the three drugs were administered to groups of rats at 10 min before or after the exposure to nickel carbonyl, sodium diethyldithiocarbamate was the most effective antidote. In contrast, then the drugs were administered at 6 hr after exposure to nickel carbonyl, D-penicillamine was the most effective antidote. Based upon the combined results of 4 sets of experiments, sodium diethyldithiocarbamate and D-penicillamine were significantly more effective than triethylenetetramine. The authors recommend that sodium diethyldithio-carbamate should remain the chelating agent of choice for therapy of nickel carbonyl poisoning. If sodium diethyldithiocarbamate is not available or if its use is contraindicated, D-penicillamine might be considered as an alternative chelating agent.

Animals↗