Effect of chronic maternal drug addiction on placental drug metabolism.

Microsomes were prepared from the term placentas of 5 drug-dependent and 4 normal (control) mothers and from the livers of 3 normal fetuses (gestational age = 22-24 weeks) to determine if chronic maternal drug addiction can induce metabolic pathways in the placenta which are utilized in the biotransformation of drugs of abuse. Using as model substrates aminopyrine for demethylation, aniline for hydroxylation, and bilirubin for conjugation, we observed little to none of substrate biotransformation in both drug-dependent and control placentas. Similarly, such enzymatic activity in the fetal liver was also low. We conclude that chronic maternal addiction does not induce metabolic pathways in the placenta for the biotransformation of drugs of abuse.

Influence of breast-feeding on the restoration of the low serum concentration of vitamin E and beta-carotene in the newborn infant.

Vitamin E and beta-carotene are two important natural antioxidants. However, the mean (+/- SD) serum concentrations of beta-carotene in the cord blood of term (17.9 +/- 4.4 micrograms/dl) and preterm (14.04 +/- 4.7 micrograms/dl) infants are one eighth the concentration in the maternal serum (131 +/- 43 micrograms/dl). Likewise the serum concentrations of vitamin E in the term (0.31 +/- 0.09 mg/dl) and preterm (0.29 +/- 0.08 mg/dl) infants are one-third the concentration in the maternal serum (0.97 +/- 0.16 mg/dl). Human breast milk, particularly colostrum, contains very high concentrations of both vitamin E (3.28 +/- 2.93 mg/dl) and beta-carotene (213 +/- 166 micrograms/dl). Thus the breast-fed, term infant attains serum levels of both vitamin E and beta-carotene comparable to those in the adult within 4 to 6 days of breast-feeding. This study shows that the seeming barrier in the fetus to access to the antioxidants vitamin E and beta-carotene, in rapidly corrected and the substances are replenished postnatally through breast-feeding. This study therefore alludes to the possible role of breast-feeding in providing for the infant's defense against oxygen toxicity.

The biosynthesis, processing, and secretion of laminin by human choriocarcinoma cells.

Laminin, a glycoprotein component of basal laminae, is synthesized and secreted in culture by a human malignant cell line (JAR) derived from gestational choriocarcinoma. Biosynthetically labeled human laminin subunits A (Mr approximately 400,000) and B (Mr = 200,000 doublet) are glycoslyated with asparagine-linked high mannose oligosaccharides that are processed to complex oligosaccharides before the laminin molecule is externalized by the cell. The rate-limiting step in the processing of the asparagine-linked glycans of laminin is at the point of action of alpha-mannosidase I since the principal laminin forms that accumulate in JAR cells contain Man9GlcNAc2 and Man8GlcNAc2 oligosaccharide units. The combination of subunits to form the disulfide-linked laminin molecule (Mr approximately 950,000) occurs rapidly within the cell at a time when the subunits contain these high mannose oligosaccharides. The production of laminin is limited by the availability of the A subunit such that excess B subunit forms accumulate intracellularly as uncombined B and a disulfide-linked B dimer. Pulse-chase kinetic studies establish these B forms as intermediates in the assembly of the laminin molecule. The fully assembled laminin undergoes further oligosaccharide processing and translocation to the cell surface, but uncombined B and B dimer are neither processed nor secreted to any significant extent. Therefore, laminin subunit combination appears to be a prerequisite for intracellular translocation, processing, and secretion. The mature laminin that contains complex oligosaccharides does not accumulate intracellularly but is rapidly externalized upon completion, either secreted into the culture medium (25%) or associated with the cell surface (75%) as determined by susceptibility to degradation by trypsin. About one-third of the laminin molecules secreted or shed by JAR cells into the chase medium contain a smaller A subunit form that appears to have been modified by limited proteolytic cleavage. The putative proteolytic event is closely timed to the release of the laminin into the culture medium.

Red cell membrane lipid peroxidation and hemolysis secondary to phototherapy.

The exposure of red cells to phototherapy light in the presence of a sensitizer (bilirubin) resulted in oxidative injury to the red cell membrane as manifested by a significant increase in the concentration of the products of lipid peroxidation (TBA reactants and diene conjugation) in the membrane and hemolysis. To induce a photo-oxidized membrane injury, the sensitizer (bilirubin) has to be membrane bound. Thus, by altering the availability of free bilirubin in the red cell suspension through changes in the molar concentration ratio of bilirubin to albumin, one is able to regulate the occurrence and extent of the oxidative red cell membrane injury. The clinical implications of these findings are discussed.

[The effect of graduated radiation doses on the follicular apparatus of the ovaries and the adenohypophysis in sheep]. / Vplyv stupnovaných dávok ziarenia na folikulárny aparát vajecníkov a na adenohypofýzu oviec.

Gradually increased radiation doses were applied directly to the ovaries of laparotomized ewes. The effect of these doses was studied as exerted on the qualitative and quantitative changes in the follicular apparatus of the ovaries and adenohypophysis of ewes in anoestrus and upon the recovery processes later on after irradiation. The ovaries irradiated with the dose of 4.79 Gy were found to be heavier when examined after some time from irradiation. The 10th and 30th day from irradiation the number of tertiary follicles decreased, the 100th day from irradiation their number increased to a four-fold level, as compared with the 10th day. Adenohypophysis showed a gradual growth of the number of PAS-positive cells. After the irradiation of ovaries with the dose of 9.57 Gy the ovaries showed the lowest rate of damage on the 10th day from irradiation; the 30th and 100th day from irradiation all the present tertiary follicles were in the state of atresia. In comparison with the control group, the amount of gonadotropic cells of adenohypophysis gradually increased, recovering from a rapid drop after irradiation. When the ovaries were irradiated with the dose of 19.14 Gy, all the tertiary follicles were in the state of atresia and the number of PAS-positive cells of adenohypophysis was lower in comparison with the control group.

[Karyometric changes in the neurons of the hypothalamic and ependymal nuclei of the 3d cerebral ventricle in sheep after administration of Gn-RH and subsequent irradiation]. / Karyometrické zmeny neurónov jadier hypotalamu a ependýmu tretej mozgovej komory oviec po podaní Gn-RH a následnom oziarení.

Caryometric analysis was used for the study of changes in the cell nucleus volume of the neurons of nucleus paraventricularis, nucleus arcuatus, and ependyma of the third cerebral ventricle of sheep after the administration of Gn-RH, followed by exposure to X-rays. The test animals were 12 ewes in physiological anoestrus and two rams. The trials were conducted in spring. The first group of four sheep and two rams were left as controls; in the ewes of the second group the hypothalamo-hypophysial region was irradiated by exposure to 516.5 mC/kg (200 R); in the four ewes of the third group, ovaries were directly irradiated at laparotomy by exposure to 64.4 mC/kg (250 R). The ewes of the second and third group were treated with an i. m. administration of 400 micrograms Gn-RH per head before irradiation. The excisions were collected and processed the tenth day from irradiation. The studied material was fixed by injection of 10% formalin and finished by another dose of 10% formalin after the excision of the brains. The paraffin slices were stained with haematoxylin-eosine. The caryometric analysis was performed at 3000-fold magnification, 200 cells being measured in each sample. Changes in neurosecretory cells were described in the regions of nucleus paraventricularis, nucleus arcuatus and in the ependyma of the third cerebral ventricle. The results of the caryometric analysis of nucleus paraventricularis and nucleus arcuatus suggest that the administration of Gn-RH and irradiation of the hypothalamo-hypophysial region, and direct irradiation of ovaries, stimulate the studied cerebral structures. The changes observed in the ependyma of the third cerebral ventricle after the administration of Gn-RH and subsequent irradiation of the hypothalamo-hypophysial region are insignificant; it is only after the direct irradiation of ovaries that these cells are inhibited by an indirect effect through the feedback mechanism.

The garland type of acute postinfectious glomerulonephritis: morphological characteristics and follow-up studies.

Among 44 patients with acute post-infectious GN, we found 11 cases (10 male, 1 female) displaying an immunohistologically and electron microscopically characteristic "garland pattern". Numerous sub-epithelial deposits of the "hump" type with characteristic patchiness correspond in the electron micrograph to densely packed deposits (IgG, always combined with C3, more rarely also with IgM) demonstrable immunohistologically on the peripheral loops. On the other hand, sub-endothelial, mesangial and intramembranous deposits are less prominent. Clinically, the patients have a strikingly high proteinuria. Follow-up studies have revealed that in a proportion of the patients both the clinical and the morphological findings can regress after a month long course. These are mainly younger patients. On the other hand, in another group of cases (mainly older patients) both the clinical and the morphological findings persist even after months. Within acute post-infectious GN, the "garland type" appears to form a particular group in which a large proteinuria (with or without nephrotic syndrome) and a tendency to chronicity or at least to a protracted course is present in a relatively high percentage.

[Follow-up study on the hemostatic effect of the Vasolamin preparation in domestic animals]. / Sledovanie hemostatického úcinku preparátu vasolamin u domácich zvierat

In this paper the haemocoagulative effect of the Vasolamin preparation was examined after intravenous application in cattle, sheep, and horses by means of tests. After a laboratory confirmation of the coagulative effect of the tested preparation we used it for the purpose of haemostasis in the clinical practice. After an administration of the preparation faster coagulation of the blood was observed in all examined animals. The setting in of the effect could be observed already after 5 minutes, the maximum effect was recorded between the 15th and 30th minutes after application, and the effect lasted, although gradually weakened, for one to two hours. In the case of bleeding clinical patients the application of Vasolamin was always successful.