Biomedical subjects
Publications and source records attributed to L Lakatos.
In the liver of neonate rats and in tissues of adult rats a study was made of the effect of D-penicillamine treatment in vivo on the enzymes of peroxide metabolism, lipid peroxidation and other components. It was found that D-penicillamine primarily acts by decreasing lipid peroxidation, thus stabilizing the membrane.
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D-penicillamine, a drug used clinically for the treatment of neonatal hyperbilirubinaemia, was tested for interference with the binding of bilirubin to human serum albumin by three methods: 1) The peroxidase technique, investigating the effect of D-penicillamine on the equilibrium concentration of unbound bilirubin in a solution containing a molar excess of albumin; 2) the MADDS method, measuring the concentration of vacant bilirubin binding site on albumin in a solution of pure albumin, or infant blood serum, with added D-penicillamine; and 3) injection of D-penicillamine into Gunn rats and determination of any decrease of plasma bilirubin which would be caused by displacement of the pigment. Results were negative in all cases. Quantitatively, the doses of D-penicillamine used clinically cannot displace bilirubin from its binding to albumin. The ameliorating effect on hyperbilirubinaemia in the newborn must be due to some other mechanism.
Concentrations of albumin, IgG, IgA, IgM, alpha 1-acid glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, transferrin, haptoglobin, and coeruloplasmin were determined by radial immunodiffusion in the blood sera and bronchial washings of 8 patients without clinical, radiologic or bronchoscopic evidence of lung diseases. The local production of the proteins was calculated with a formula used by Deuschl and Johansson for the estimation of local synthesis of bronchial immunoglobulins. The formula was completed by a reduction factor established by the authors, based on their previous investigations. The calculations indicated that the individual proteins were secreted locally in various percentages of the total amount found in the secretion, as follows: IgG, 37%; IgA, 84.5%; transferrin, 44.5%, alpha 1-antitrypsin, 15.2%; coeruloplasmin, 11.3%. Local synthesis of IgM was found only in 3 patients. The alpha 1-acid glycoprotein and the haptoglobin do not seem to be secreted locally by the normal bronchial mucosa; they reach the mucus from blood only, through ultrafiltration.
Superoxide dismutase activity of alveolar macrophages, lung, liver, retina and choroid has been studied in rats and rabbits exposed to oxygen at high concentration by itself and in combination with D-penicillamine. Prolonged hyperoxia caused an increase in superoxide dismutase activity while D-penicillamine was found to inhibit the inductive effect of oxygen. It is assumed that the antioxidative effect of D-penicillamine makes it unnecessary to augment the production of superoxide dismutase.
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This study comprises 120 full-term infants with ABO hemolytic disease admitted to the neonatal department during a period of 60 months from 1970-1975. During the first 30 months newborns (n = 61) received no D-penicillamine therapy, whereas all infants (n = 59) received this treatment (300-400 mg/kg/day, divided into 4 equal doses, for 2-5 days) during the last 30 months. The patients were further subdivided into two groups according to the point of time when D-penicillamine treatment was begun, viz. group I (34 treated and 34 control infants) within the first 24 h of life; group II (25 treated and 27 control infants) after the third day of life. In group I D-penicillamine therapy caused a marked decline of serum bilirubin concentrations at a time when such levels were rising in the control infants. The number of exchange transfusions per infant was 1.32 in the control and 0.11 in the D-penicillamine-treated infants. In group II D-penicillamine considerably reduced the number of exchange transfusions (0.70:0.24 = control:treated) but the difference was statistically not significant. In the latter patients the mean bilirubin values showed a smaller difference compared to the controls than in group I. Since group I represented the results of early or preventive treatment, while group II those of late or therapeutic treatment, it is obvious that, for ensuring success, D-penicillamine treatment should be begun as early as possible in ABO hemolytic disease of the newborn.
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A total 330 newborns suffering from haemolytic disease of the newborn and hyperbilirubinaemia was treated with D-penicillamine. The therapy resulted in a significant decrease in the frequency of exchange transfusions and of high serum bilirubin levels among preterm and fullterm babies with or without sensitization. Concerning the drug's mechanism of action, reduction of the bilirubin level is achieved by means of the copper stored in the liver. The intravenous route is suggested for application of the drug. In preterm infants D-penicillamine treatment proved more effective than phototherapy.