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PubMedDate not supplied

Developmental toxicity of cysteamine in the rat: effects on embryo-fetal development.

The reproductive and developmental safety of cysteamine has become an important issue to children with cystinosis because renal transplants and treatment with cysteamine reduce the complications associated with cystinosis and increase the lifespan of the affected children. In addition, there is the potential to decrease the severity or the incidence of renal Fanconi syndrome with administration of cysteamine to pregnant women carrying fetuses with cystinosis, and to ease significantly the burden of this disease throughout their lives. If cysteamine increases significantly the risk of fetal death, growth retardation or birth defects at doses used to treat women with cystinosis, treatment of the affected female should cease during pregnancy and would not be considered for fetal treatment. The goal of this study was to assess the developmental safety of exposure in utero to cysteamine in the rat. Pregnant rats were given cysteamine (as phosphocysteamine) from day 6.5 through day 18.5 postconception and fetuses were assessed for survival, growth, and structural abnormalities on day 20.5. Cysteamine was administered orally in doses of 0, 37.5, 75, 100, or 150 mg/kg/day. Cysteamine produced dose-dependent developmental toxicity with an apparent no adverse effect observed level of 75 mg/kg/day. Specific malformations were associated with this effect (cleft palate, kyphosis), as well as intrauterine growth retardation and fetal death at 100-150 mg/kg/day, without signs of maternal toxicity. Investigations continue into the mechanism for the developmental toxicity of cysteamine.

Administration, Oral↗
PubMed1988

Campylobacters and impaired fetal development in mice.

Intravenous injection of eight human strains of Campylobacter fetus ss fetus and Campylobacter jejuni into mice at various stages of pregnancy demonstrated significant strain differences in ability to affect implantation of the fertilised ovum and to cause resorption of the mouse fetus. Implantation was significantly impaired when C. fetus ss fetus was injected intravenously on day 2 of pregnancy, but no effect was observed in mice receiving C. jejuni. On day 6 of pregnancy, before the development of placental circulation, both C. fetus ss fetus and C. jejuni impaired fetal growth; one strain of C. jejuni had a greater effect than others of the same species. In animals inoculated on day 13 of pregnancy, after the development of placental circulation, six of the eight campylobacter strains caused resorption of the mouse embryos. A similar effect on the embryos was observed after injection of heat-killed organisms, and endotoxin-like substances may have been responsible. It is also suggested that factors other than endotoxin-like substances have a deleterious effect on embryonic growth.

Animals↗
PubMed1993

CD5 antigen-positive B lymphocytes in human B cell ontogeny during fetal development and after autologous bone marrow transplantation.

We examined bone marrow and peripheral blood specimens from pediatric acute lymphoblastic leukemia (ALL) patients after autologous bone marrow transplantation (BMT) as well as fetal lymphohematopoietic tissues for the presence of CD5+ B lymphocytes. CD5+ B lymphocytes represented 23.6 +/- 0.7% of CD19+ fetal spleen B lineage lymphoid cells, 24.2 +/- 2.5% of CD19+ fetal bone marrow B lineage lymphoid cells and 18.1 +/- 1.7% of CD19+ fetal liver B lineage lymphoid cells. By comparison, in normal pediatric bone marrow samples, only 1.5 +/- 0.3% of lymphoid cells and 4.3 +/- 0.2% of CD19+ B lineage lymphoid cells expressed CD5 antigen. Similarly, very few CD5+CD19+ cells (< or = 2% of lymphoid cells) were found in day 30 and day 100 post-BMT bone marrow or peripheral blood specimens from B lineage ALL patients undergoing autologous BMT using autografts purged ex vivo with B43(anti-CD19)-PAP immunotoxin plus 4-hydroperoxycyclophosphamide (4-HC). Two bone marrow samples that were obtained and analyzed 1 year post-BMT contained only 2 to 4% CD5+CD19+ cells, accounting for 5 to 7% of the total CD19+ population. The fraction of CD5+ B lymphocytes in post-BMT bone marrow samples was not greater than the fraction of CD5+ B lymphocytes in normal healthy bone marrow.

Antibodies, Monoclonal↗
PubMed1989

Estrogen receptors in the rhesus monkey brain during fetal development.

Estrogen receptor (ER) levels were measured in brain tissue cytosol from fetal male and female rhesus monkeys at Days 70, 100 and 160 postconception. The brain regions which were examined included medial basal hypothalamus (MBH), amygdala (AMG), cerebral cortex (CTX) and cerebellum (CB). For comparison, brain tissues were also obtained from an adult female, and muscle (MUS) and genital tract (GEN, ovaries + uterus) ER values were measured in several Day 70 fetuses. Tissues were dissected and homogenized as previously described. Cytosol was passed through a microcolumn of Lipidex 1000 to remove interfering lipids and incubated with [3H]Moxestrol (4 nM) in the presence or absence of 500 nM Moxestrol. Incubations were carried out for 24 h at 4 degrees C, and free and bound ligand separated by Sephadex LH-20 gel filtration. In one case (Day 160 male fetus), saturation analysis yielded an estimate of apparent Kd of 0.46 x 10(-9) M and indicated that maximal specific binding was achieved at a ligand concentration of 1-2 nM. There was no sex difference at any stage of development (ANOVA). A significant age effect (P less than 0.002) was noted for the MBH and CB but not for any of the other tissues examined. In the MBH the significance of this effect was due to a progressive increase in ER levels with fetal age and into adulthood. In contrast, CB levels exhibited a progressive decline with age. These studies revealed that the ER is present during brain development. Thus any estrogens derived from the aromatization of circulating fetal androgens could potentially exert an influence upon brain development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗