The transplacental transfer, irreversible binding, and ultrastructural lesions in the fetal adrenal cortex were studied following single injections of the persistent DDT-metabolite 3-methylsulphonyl-DDE (MeSO2-DDE) in pregnant C57B1 mice. Tape-section autoradiograms of fetuses on gestation days 12 to 17 revealed a high and tissue-specific accumulation of MeSO2-DDE-14C-derived radioactivity in the fetal adrenal gland. On gestation day 12 the adrenal radioactivity could be extracted with organic solvents, whereas on days 13 to 17 the radioactivity in the adrenal was irreversibly bound and could not be extracted from the tissue. As determined by computer-assisted image analysis of autoradiograms, the uptake of radioactivity in the fetal adrenals increased continuously with gestational age. Electron microscopy revealed mitochondrial degeneration and vacuolation in fetal adrenal cortex cells following injection of MeSO2-DDE (25 mg/kg b.w.) to the pregnant dam. The lesions were clearly visible on days 14 to 15 but most pronounced on days 16 to 17. Administration of the cytochrome P450(11 beta) inhibitor metyrapone to pregnant dams (gestation day 17) reduced the mitochondrial toxicity induced by MeSO2-DDE in the fetal adrenal cortex. In conclusion, the adrenocorticolytic DDT metabolite MeSO2-DDE is transformed to a reactive, cytotoxic metabolite in the fetal adrenal cortex from its earliest stage of development. Hence, the activating cytochrome P450 form, previously proposed to be P450(11 beta), seems to be expressed during gestation days 12 to 13 in the adrenal cortex in the mouse fetus.

Adrenal Cortex↗

PubMedDate not supplied

[The growth rate of healthy children in the first 16 years: Bonn-Dortmund longitudinal developmental study].

Standards for supine length/height velocity from birth to 16 years (percentiles, mean and standard deviation) are presented, based on the longitudinal growth studies from Bonn and Dortmund. During the first two years of life growth velocity is twice to three times higher as in the following years. Many things point to the growth velocity during the first two years being of decisive significance for the observed secular acceleration of height. International comparisons with other longitudinal growth studies show a trend of somewhat higher growth velocity of the children from the Bonn and Dortmund studies.

Adolescent↗

PubMedDate not supplied

[Anterior fontanelle as a window to the brain--normal values and timing of closure].

Nowadays an exact examination of the infant's brain is possible through the anterior fontanelle by ultrasonography (US); however for that a certain minimal size of the fontanelle is necessary. In the literature standards for size and timing of closure are scarce. In the Bonn Longitudinal Study of growth and development of preterm infants in comparison with full term infants also the length (anterior-posterior diameter) and width (transversal) of the anterior fontanelle have been measured monthly from birth, and the timing of closure was registered. As a measure of fontanelle size here the width (transversal diameter) is used. For the full term infants the width (50. percentile) at birth is 2.0 cm; it decreases to 0.6 cm until the age of 12 months. The great variability of fontanelle size observed in the Bonn study is also confirmed in the literature. In the appropriate for gestational age (AGA) preterm infants the anterior fontanelle (50. percentile) increases between 32 and 40 postmenstrual weeks from 1.8 to 2.5 cm and is then significantly greater than in the full term infants. At least at the age of 3 months there is no significant difference between the AGA preterm infants and the full term infants, either for the boys or for the girls. For the boys, in spite of their significantly greater head circumference there is a tendency to have a smaller fontanelle than the girls; the difference is at no age significant. For preterm as well as for full term infants timing of closure occurs somewhat earlier in the boys than in the girls.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMedDate not supplied

Distribution and effect of some polychlorinated biphenyls in the hemopoietic tissues.

Distribution of 14C-labeled 2,4',5-trichlorobiphenyl 2,2',4,4',5,5'-hexachlorobiphenyl, and 2,2',3,3',4,4',5,6'-octachlorobiphenyl was studied in the hematopoietic tissues of squirrel monkey and mice (C67 Bl) using whole-body autoradiography. An accumulation of radioactivity was seen in the bone marrow of monkey 24 h and 48 h after iv injection of hexachlorobiphenyl and trichlorobiphenyl, respectively. High concentration of radioactivity was also observed in the bone marrow of normal mice injected iv with octachlorobiphenyl. A combination of whole-body autoradiography and spleen-colony assay in supralethally irradiated mice implanted with syngeneic bone-marrow cells indicated the major part of radioactivity to be localized outside the bone-marrow hemic compartment, probably in the fat. No effect of hexachlorobiphenyl but a significant inhibition with octachlorobiphenyl (10(-5) M) and especially trichlorobiphenyl (10(-5) M) was seen on the formation of granulocytic colonies from mouse progenitor cells in vitro.

Animals↗

PubMedDate not supplied

3,3',4,4'-Tetrachlorobiphenyl. Excretion and tissue retention of hydroxylated metabolites in the mouse.

The coplanar 3,3',4,4'-tetrachlorobiphenyl (TCB) was given orally to mice and the metabolite patterns in feces, urine, liver, and adipose tissue were examined. In feces, 80% of the dose was excreted within 5 days. 5-Hydroxy-, 6-hydroxy-TCB, 4-hydroxy-3,3',4',5-tetrachlorobiphenyl, and unmetabolized TCB were identified by comparison to synthetic standards (GC/MS). 4-Hydroxy-trichlorobiphenyl and a dihydroxy-trichlorobiphenyl were indicated by the fragmentation pattern of the corresponding methylated derivatives by GC/MS. In urine, 4.9% of the TCB dose was excreted mainly as conjugates. After hydrolysis, TCB and seven hydroxylated metabolites were detected; 2-, 5-, and 6-hydroxy-TCB and 4-hydroxy-3,3',4',5-tetrachlorobiphenyl were identified and two dihydroxy-tetrachlorobiphenyls were indicated. The major compound detected after hydrolysis of urine was a dihydroxy-trichlorobiphenyl. TCB was the major compound present in the liver, while a minor portion was due to 4-hydroxy-3,3',4',5-tetrachlorobiphenyl. TCB, 4-hydroxy-3,3',4',5-tetrachlorobiphenyl, and 5- and 6-hydroxy-TCB were present in adipose tissue. In addition, radiolabeled material was present in a lipid fraction obtained after gel permeation chromatography of all samples except urine, indicating the presence of TCB metabolites with lipid characteristics.

Adipose Tissue↗

PubMedDate not supplied

Target cells for the polychlorinated biphenyl metabolite 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl in lung and kidney.

Light microscope autoradiography was used to determine the cellular localization of the polychlorinated biphenyl metabolite 4,4'-bis([14C] methylsulfonyl)-2,2',5-5'-tetrachlorobiphenyl ([3H]TCB) in the lung and kidney of mice and rats. Microautoradiograms prepared from thaw-mounted freeze sections showed that the radioactivity in the lung was localized in the bronchiolar lumen and epithelium. In methacrylate sections (74-82% of radioactivity extracted), a highly selective labeling was registered in the apical cytoplasm of the Clara cells. A pronounced labeling was present also in certain goblet-like cells containing periodic acid-Schiff-positive granules. Gel permeation chromatography and density gradient centrifugation showed that 80-95% of the radioactivity in lung lavage fluid was bound to a specific protein previously characterized in rat and mouse lung cytosol. The protein appeared to be enriched in the lavage fluid, as compared to lung cytosol. These data suggest that [3H]TCB binds to a protein residing in the Clara and goblet-like cells and that the labeled TCB-protein complex is subsequently secreted into the airway lumen. As shown by microautoradiography, the radioactivity in the kidney was confined to a restricted portion of the nephron, predominantly to the apical region of the proximal tubular cells.

Animals↗