Search PubMed⌕ Search

Biomedical subjects

H Shen

Publications and source records attributed to H Shen.

At least 253 records · Page 14Linked to original sources
PubMed1997

Coroner-reviewed infant and toddler deaths. Many "undetermineds" resemble homicides.

Although homicide is a leading cause of death of infants and toddlers, there is some suspicion that an unknown number of additional deaths are unrecognized homicides. The authors used California mortality data from 1969 to 1991 to examine 12,246 injury deaths that occurred before age 5. Characteristics of the dead child, injury event, and postmortem were compared for accidents, homicides, and undetermined deaths. A logistic model was developed to differentiate homicides from accidental deaths and then was used to predict whether undetermined deaths were likely to be homicides or accidents. Unlike accidental deaths, undetermineds and homicides had similar distribution patterns of age, race, sex, and place of injury. The predictive model indicates that 43.8% of the undetermined injury deaths were similar to homicides on several characteristics. True rates of homicide for infants and toddlers may, unfortunately, be nearly one fifth and one tenth higher, respectively, if the undetermined deaths that resemble homicides are taken into account.

Accidents↗
PubMed1997

Antenatal betamethasone therapy augments isoproterenol and prostaglandin E2-mediated relaxation of preterm ovine pulmonary veins.

Antenatal glucocorticoid therapy improves pulmonary function in preterm newborns. We have determined the effect of antenatal glucocorticoid therapy on isoproterenol and prostaglandin (PG) E2-mediated relaxation in preterm ovine pulmonary veins after birth. Ovine fetuses (121 and 126 d of gestation; term = 150 d) received an ultrasound guided intramuscular injection of betamethasone, 0.5 mg/kg, or saline. Lambs were delivered 15 or 48 h later, ventilated for 3 h, and killed. Isolated fourth generation pulmonary veins were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2, 5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to U46619, isoproterenol and PGE2 induced greater relaxations of pulmonary veins of betamethasone-treated lambs than those of control. Forskolin, an activator of adenylate cyclase, caused greater relaxation in veins of betamethasone-treated lambs than in those of controls. A greater relaxation of veins treated with betamethasone than that of control veins also occurred in the presence of isobutylmethylxanthine, an inhibitor of phosphodiesterases. All vessels relaxed similarly to 8-bromo-cAMP, a cell membrane-permeable analog of cAMP. When stimulated with isoproterenol, PGE2, and forskolin, adenylate cyclase activity of crude membrane preparations of pulmonary veins treated with betamethasone was greater than that of controls. These results demonstrate that antenatal betamethasone therapy potentiates isoproterenol and PGE2-mediated relaxation of pulmonary veins of preterm lambs; an enhanced adenylate cyclase activity explain in part the effect of antenatal glucocorticoid therapy on pulmonary veins of preterm lambs.

Adenylyl Cyclases↗
PubMed1997

[Influence of transfection of sense- and antisense-TGF beta 1 gene on human pulmonary giant cell carcinoma cell proliferation].

OBJECTIVE: To investigate the effect of human sense- and antisense-transforming growth factor beta 1 (TGF beta 1) gene on human pulmonary giant cell carcinoma cell (PLA-801D) proliferation. METHODS: PLA-801D cells were transfected with an expression vector containing a full length human sense- or antisense-TGF beta 1 gene by gene transfer. The changes of cell proliferation, expressions of nm23 mRNA and c-myc mRNA and the feature of apoptosis were studied on transfected cells and untransfected cells. RESULTS: The cells transfected by sense-TGF beta 1 gene showed higher TGF beta 1 activity in the conditioned media, growth inhibition in vitro and decreased coloning formation in anchorage-independent assay. The tumorigenic rate was reduced about 47%, the metastasis was inhibited in athymic nude mice as compared with untransfected cells group. The mechanism of such changes described may be associated with the higher expression of nm23 mRNA, and the lower expression of c-myc mRNA as well as the apoptosis in sense-TGF beta 1 gene transfected cells. However, opposing changes were observed in the antisense-TGF beta 1 gene transfected cells. CONCLUSION: TGF beta 1 acts as a negative growth regulator of the PLA-801D in vitro as well as in vivo.

Animals↗
PubMed1997

[Comparative studies on pharmacological and toxic actions of raw fructus Psoraleae and its salt-baked and improved salt-baked products].

The pharmacological and toxic actions of raw Fructus Psoraleae and its salt-baked, and improved salt-baked products were comparatively studied. The leucogenic action of the improved salt-baked product was more effective than that of the original salt-baked one. But no significant difference in antidiarrheal or antiandrogenoid effect was found between the two salt-baked products. The toxicity(LD50 and the injury on kidney) of the improved salt-baked product was lower than that of the salt-baked. one. The results indicate that this improved processing method would contribute to increasing the efficacy and decreasing the toxicity of Fructus Psoraleae.

Androgen Antagonists↗
PubMed1997

[Toxic studies on various processed products of Fructus Psoraleae].

Toxic studies on Fructus Psoraleae (FP) and its processed products are carried on. LD50 is 37.7 +/- 0.54 g crude drug/kg in oral administration of raw FP in comparison with 43.25 +/- 6.1/kg in that of Salt-bake one in mice. When 5.0 g/kg is given by oral for 14 days, the wet weight of testicles, preputial galnds, prostate and semianl vesicle is decreased in raw FP and its stir-bake tested groups. The wet weight of preputial glends, prostate, seminal vesicle in Lei Gong's Procession group, or prostate, and seminal vesicle in salt-steam group is also decreased to a certain extent. But no significant change on the weight of those sex organs is found in liquor-bake or salt-bake procession group, The glomerulal cell hyperplasia and cloudy swelling of renal tubules are induced by administration of raw FP in pathological examination.

Animals↗
PubMed1997

[Surface-enhanced Raman spectra studies on four complexes derived from D-glucosamine and alpha-glycine and their effect on DNA].

Raman scattering of four complexes derived from d-glucosamine and alpha-glycine and their effects on DNA were studied with surface-enhanced Raman spectra (SERS). It was found that their SERS had shown little difference for their similar structural. Their interaction abilities on DNA were poor according to the change of their SERS spectrun after adding DNA to their water solution except for Co(III)GluG, which has strong effect on DNA. NiGluG's adsorptive ability on Ag sol is the strongest among other three complexes.

DNA↗
PubMed1997

Enhancement of calcium cycling by atrial sarcoplasmic reticulum after cardiopulmonary bypass and cardioplegia during open heart surgery.

We studied myocardial Ca2+ cycling during cardiopulmonary bypass and cold-blood cardioplegia (CPB/CBC) in patients with coronary heart disease undergoing coronary artery bypass grafting. Right atrial biopsies were taken from 13 patients before and after CPB/CBC: after pericardiotomy, immediately after aortic cross-clamp removal, and following termination of CPB/CBC. Changes in ionized Ca2+ concentration (nM) were monitored with indo 1 during Ca2+ uptake and Ca2+ release by sarcoplasmic reticulum in a medium containing 1% homogenized myocardium. Ryanodine inhibition was used to estimate Ca2+ release channel activity. With CPB/CBC, the initial Ca2+ concentration of reaction media increased 33%, (962 +/- 150 to 1262 +/- 106 nM; mean +/- SD). Ca2+ cycling increased asymmetrically, 108% for Ca2+ uptake (3.91 +/- 1.32 to 8.15 +/- 3.17 nM/s), 197% for Ca2+ release (0.90 +/- 0.80 to 2.73 +/- 1.13 nM/s), and 68% for the ratio of Ca(2+)-release to Ca(2+)-uptake activities (0.22 +/- 0.14 to 0.37 +/- 0.13). The dissociation constant of the Ca2+ pump for Ca2+ was unaltered by CPB/CBC (289 +/- 76 nM). During the time period that was studied post-bypass, Ca(2+)-pump activity remained increased, although the Ca(2+)-channel activity returned to pre-bypass values (all p < 0.05). We conclude that CPB/CBC produces increased myocardial Ca2+ load, twofold increased Ca2+ uptake, and threefold increased Ca2+ release by sarcoplasmic reticulum.

Calcium↗
PubMed1997

Importance of glutathione and associated enzymes in drug response.

Maintenance of cellular homeostasis is a critical survival trait in tumors when exposed to anticancer drugs. Because conjugation and elimination of drugs and their metabolites is dependent upon sequential and coordinated pathways, acquired drug resistance through a gradual adaptive response would rarely be expected to be the consequence of changes in the expression of one gene product. We have used a number of drug-resistant human cell lines to characterize those genes that are implicated in maintaining a resistant phenotype. Human HT29 colon cancer cells chronically exposed to ethacrynic acid (EA) [a glutathione (GSH) and glutathione S-transferase (GST) modulator] have acquired resistance to the drug. Commensurate with resistance, EA is more effectively conjugated to GSH and effluxed from the resistant cells. Using directed and random (differential display) approaches, a number of detoxification and/or protective gene products have been shown to be expressed at elevated levels. These include: gamma-glutamyl cysteine synthetase (gamma-GCS, the rate-limiting enzyme in GSH biosynthesis); GST pi (the enzyme catalyzing the conjugation reaction); multidrug resistance associated protein (MRP) (the membrane pump responsible for effluxing the conjugate from the cell interior). In addition, other gene products not directly linked with EA metabolism were induced, including dihydrodiol dehydrogenase (an alpha-ketoreductase) (30-fold), DT-diaphorase (threefold), and a transcriptional regulator SSP 3521 (threefold). HL60 cells resistant to a GSH paralog Ter199 also show increased expression of some of these gene products. Furthermore, an adriamycin-resistant human HL60 cell line also shows overexpression of GST pi, gamma-GCS, and MRP, but in addition has approximately 20-fold more DNA-dependent protein kinase catalytic subunit (DNA-PKcs). This enzyme is an early stress response gene that can phosphorylate and activate downstream transcription factors. Such overexpression could impact on the transcriptional control of the other detoxification gene products. Both adriamycin and a typical drug-GSH conjugate (APA-SG) are inhibitors of DNA-PK. Because cellular levels of these conjugates would presumably be a good indicator of stress, it would seem reasonable to speculate that DNA-PK may act as a receiver and transmitter of signals that are crucial to the drug-resistant phenotype. Additionally, this enzyme may prove to be a potentially important target for drug design based upon the inhibitory activity of GSH conjugates.

Drug Resistance, Neoplasm↗
PubMed1996

Reduction of CDP-diacylglycerol synthase activity results in the excretion of inositol by Saccharomyces cerevisiae.

A yeast mutant, cdg1, was isolated on the basis of an inositol excretion phenotype. This mutant exhibited pleiotropic deficiencies in phospholipid biosynthesis, including reduced levels of CDP-diacylglycerol (DAG) synthase activity (Klig, L. S., Homann, M. J., Kohlwein, S. D., Kelley, M. J., Henry, S. A., and Carman, G. M. (1988) J. Bacteriol. 170, 1878-1886). In this study we present evidence that the molecular basis for the inositol excretion phenotype is a G305/A305 point mutation (Cys102 --> Tyr substitution) within the CDS1 gene (encodes CDP-DAG synthase) of this mutant. Expression of CDP-DAG synthase activity from a plasmid-borne copy of the CDS1 gene in the cdg1 mutant was not down-regulated, and this expression also corrected the inositol excretion phenotype. Introduction of the above mutated gene (CDS1*) controlled by its endogenous promoter on a single copy plasmid into a cds1-null background reconstituted a transformant with the cdg1 phenotype, including reduced CDP-DAG synthase activity, elevated phosphatidylserine synthase activity, and inositol excretion into the growth medium. Expression of CDS1* in a single copy in the cdg1 mutant raised CDP-DAG synthase activity from 15 to 30% of derepressed wild-type yeast levels but still did not correct the inositol excretion phenotype. CDP-DAG synthase activity was not regulated in response to precursors of phospholipid biosynthesis in the cdg1 mutant either with or without a trans copy of the CDS1* gene. An open reading frame was identified 5' to the CDS1 locus, YBR0314, which also resulted in inositol excretion when present in trans in multiple copies.

Diacylglycerol Cholinephosphotransferase↗
PubMed1996

Temporal mapping of gene expression levels during the differentiation of individual primary hematopoietic cells.

A hierarchical order of gene expression has been proposed to control developmental events in hematopoiesis, but direct demonstration of the temporal relationships between regulatory gene expression and differentiation has been difficult to achieve. We modified a single-cell PCR method to detect 2-fold changes in mRNA copies per cell (dynamic range, 250-250,000 copies/cell) and used it to sequentially quantitate gene expression levels as single primitive (CD34+,CD38-) progenitor cells underwent differentiation to become erythrocytes, granulocytes, or monocyte/macrophages. Markers of differentiation such as CD34 or cytokine receptor mRNAs and transcription factors associated with their regulation were assessed. All transcription factors tested were expressed in multipotent progenitors. During lineage-specific differentiation, however, distinct patterns of expression emerged. SCL, GATA-2, and GATA-1 expression sequentially extinguished during erythroid differentiation. PU.1, AML1B, and C/EBP alpha expression profiles and their relationship to cytokine receptor expression in maturing granulocytes could be distinguished from similar profiles in monocytic cells. These data characterize the dynamics of gene expression accompanying blood cell development and define a signature gene expression pattern for specific stages of hematopoietic differentiation.

Adult↗
PubMed1996

Structure and in vitro substrate specificity of the murine multidrug resistance-associated protein.

MRP is a recently described ATP-binding cassette transporter that confers cellular resistance to natural product cytotoxic drugs. To examine the biochemical activity and cellular physiology of this transporter, we isolated the murine MRP homologue and analyzed its in vitro substrate specificity. Murine MRP transcript is widely expressed in tissues and encodes a protein of 1528 amino acids that is 88% identical to its human homologue. Hydropathy analysis indicated that murine and human MRP, the yeast cadmium resistance transporter and the sulfonylurea receptor share a conserved topology distinguished from P-glycoprotein and the cystic fibrosis conductance regulator by an N-terminal hydrophobic region that contains several potential transmembrane domains. Drug uptake assays performed with membrane vesicles prepared from NIH3T3 cells transfected with a murine MRP expression vector revealed ATP-dependent transport for the natural product cytotoxic drugs daunorubicin and vincristine, as well as for the glutathione S-conjugates leukotriene C4 and azidophenacyl-S-glutathione. Drug transport was osmotically sensitive and saturable with regard to drug and ATP concentrations, with K(m) values of 19 microM, 19 microM, 26 nM, 17 microM, and 77 microM for daunorubicin, vincristine, leukotriene C4, APA-SG, and ATP, respectively. Consistent with broad substrate specificity, the drug glutathione conjugate APA-SG, oxidized glutathione, the LTD4 antagonist MK571, arsenate, and genistein were competitive inhibitors of daunorubicin transport, with Ki values of 32 microM, 25 microM, 1.9 microM, 108 microM, and 23 microM, respectively. This study demonstrates that the substrate specificity of murine MRP is quite broad and includes both the neutral or mildly cationic natural product cytotoxic drugs and the anionic products of glutathione conjugation. The widespread expression pattern of murine MRP in tissues, combined with its ability to transport both lipophilic xenobiotics and the products of phase II detoxification, indicates that it represents a widespread and versatile cellular defense mechanism.

3T3 Cells↗
PubMed1996

ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles establishes MRP as a broad specificity transporter.

MRP is a recently isolated ATP-binding cassette family transporter. We previously reported transfection studies that established that MRP confers multidrug resistance [Kruh, G. D., Chan, A., Myers, K., Gaughan, K., Miki, T. & Aaronson, S. A. (1994) Cancer Res. 54, 1649-1652] and that expression of MRP is associated with enhanced cellular efflux of lipophilic cytotoxic agents [Breuninger, L. M., Paul, S., Gaughan, K., Miki, T., Chan, A., Aaronson, S. A. & Kruh, G. D. (1995) Cancer Res. 55, 5342-5347]. To examine the biochemical mechanism by which MRP confers multidrug resistance, drug uptake experiments were performed using inside-out membrane vesicles prepared from NIH 3T3 cells transfected with an MRP expression vector. ATP-dependent transport was observed for several lipophilic cytotoxic agents including daunorubicin, etoposide, and vincristine, as well as for the glutathione conjugate leukotriene C4 (LTC4). However, only marginally increased uptake was observed for vinblastine and Taxol. Drug uptake was osmotically sensitive and saturable with regard to substrate concentration, with Km values of 6.3 microM, 4.4 microM, 4.2 microM, 35 nM, and 38 microM, for daunorubicin, etoposide, vincristine, LTC4, and ATP, respectively. The broad substrate specificity of MRP was confirmed by the observation that daunorubicin transport was competitively inhibited by reduced and oxidized glutathione, the glutathione conjugates S-(p-azidophenacyl)-glutathione (APA-SG) and S-(2,4-dinitrophenyl)glutathione (DNP-SG), arsenate, and the LTD4 antagonist MK571. This study establishes that MRP pumps unaltered lipophilic cytotoxic drugs, and suggests that this activity is an important mechanism by which the transporter confers multidrug resistance. The present study also indicates that the substrate specificity of MRP is overlapping but distinct from that of P-glycoprotein, and includes both the neutral or mildly cationic natural product cytotoxic drugs and the anionic products of glutathione conjugation. The widespread expression of MRP in tissues, combined with its ability to transport both lipophilic xenobiotics and the products of phase II detoxification, indicates that the transporter represents a widespread and remarkably versatile cellular defense mechanism.

3T3 Cells↗
PubMed1996

Intragenic suppressors of P-loop mutations in the beta-subunit of the mitochondrial ATPase in the yeast Saccharomyces cerevisiae.

Three intragenic second-site suppressors, P353L, T237I, and L390F, were identified that suppressed two mutations in, and one adjacent to, the P-loop in the beta-subunit of the yeast F1-ATPase. The crystal structure of bovine F1-ATPase (Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628) shows that these suppressor residues are located in the nucleotide-binding domain. Specific hypotheses have been formulated that suggest the conformational coupling of the P-loop with the suppressor sites. P353L is in a "catch" region, which forms unique interactions with the gamma-subunit in the three different conformational states of the catalytic site. The identification of this suppressor mutation demonstrates genetically that the catch region is conformationally coupled to the P-loop. T237I is shown to interact with Lys-209, which occurs just after the P-loop. This suggests that this interaction changes the conformation of the P-loop to suppress the initial mutation. L390F interacts with Ala-181, which is adjacent to the P-loop. The mechanism of this suppression is suggested to occur through the interactions of L390F with Ala-181. These results identify critical interactions that modulate the structure of the P-loop and thus the biochemistry of the enzyme.

Adenosine Triphosphatases↗
PubMed1996

Cellular and in vitro transport of glutathione conjugates by MRP.

MRP is a recently identified ATP-binding cassette transporter. We previously established that MRP confers resistance to a spectrum of natural product cytotoxic drugs [Kruh, G.D., (1994) Cancer Res. 54, 1649-1652], that expression of MRP is associated with enhanced drug efflux [Breuninger, L.M., (1995) Cancer Res. 55, 5342-5347], and that MRP transcript is widely expressed in human tissues and solid tumor cell lines [Kruh, G.D., (1995) J. Natl. Cancer Inst. 87, 1256-1258]. In the present study the relationship between MRP and drug glutathione S-conjugates was examined. We observed that MRP was labeled by azidophenacylglutathione (APA-SG), a photoaffinity analog of glutathione, and that inside-out membrane vesicles prepared from MRP-overexpressing HL60/ADR cells transported this compound. Transport into membrane vesicles was ATP-dependent, sensitive to osmolarity, and saturable with regard to APA-SG and ATP concentrations, with Km values of 15 and 61 microM, respectively. APA-SG transport was competitively inhibited by the natural product cytotoxic drugs daunorubicin, vincristine, and etoposide, with Ki values of 4.8, 3.8, and 5.5 microM, respectively. Oxidized glutathione, the drug-glutathione S-conjugate DNP-SG, the LTD4 antagonist MK571 and arsenate were also competitive inhibitors, with Ki values of 9.0, 23.4, 1.1, and 15.0 microM, respectively. Analysis of the fate of monochlorobimane in MRP transfectants revealed reduced intracellular concentrations of drug-glutathione S-conjugates associated with enhanced efflux and altered intracellular distribution. These results indicate that MRP can transport glutathione conjugates in vitro and in living cells and suggest the possibility that the transporter may represent a link between cellular resistance to some classes of cytotoxic drugs and glutathione-mediated mechanisms of resistance. In addition, the observation that both mildly cationic or neutral natural product cytotoxic drugs and anionic compounds such as DNP-SG, MK571, and arsenate are competitive inhibitors of MRP action suggests that the substrate specificity of the transporter is quite broad.

3T3 Cells↗
PubMed1996

Effects of chronic ethacrynic acid exposure on glutathione conjugation and MRP expression in human colon tumor cells.

Chronic exposure to ethacrynic acid of a subcloned HT29 human colon cancer cell line produces a 3- to 4-fold increase in the level of resistance to this agent. The resistant cells (HT6-8) have an enhanced capacity to metabolize the parent drug and efflux it from the cell. This is reflected in a 5-fold enhanced decompositioning rate constant for ethacrynic acid in HT6-8 (3.47 x 10-3 min-1) versus wild type cells (1.58 x 10-2 min-1). We observed that the glutathione conjugate of ethacrynic acid is an effective competitive inhibitor for binding to the multidrug resistance-associated protein by [35S]azidophenacyl-glutathione, a photoaffinity analog of glutathione. In addition, the HT6-8 cells overexpressed multidrug resistance-associated transcript 2- to 3-fold. These results suggest that resistance to ethacrynic acid results from a concerted, coordinate increase in defense mechanisms which detoxify the drug and remove its conjugate via plasma membrane efflux.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

The CDS1 gene encoding CDP-diacylglycerol synthase in Saccharomyces cerevisiae is essential for cell growth.

An open reading frame (CDS1) residing on chromosome II of Saccharomyces cerevisiae encodes a hydrophobic protein with a predicted molecular mass of 51,789 Da, which exhibits 29 and 37% amino acid sequence identities with CDP-diacylglycerol synthases reported from Escherichia coli and Drosophila, respectively. Induction of expression of a GAL1 promoter-driven CDS1 gene on a multicopy plasmid in a cds1 null mutant background resulted in synthase activity 10 times that of wild-type cells and an elevation in the apparent initial rate of synthesis of phosphatidylinositol relative to phosphatidylserine. Without induction, activity was reduced to 10% of wild-type levels, which was sufficient to support growth but resulted in an inositol excretion phenotype, and had an opposite effect on the above phospholipid synthesis. Null cds1 mutants were incapable of spore germination or vegetative growth and could not be complemented under uninduced conditions with a GAL1 promoter-driven CDS1 gene on a low copy plasmid. Therefore, the essential CDS1 gene encodes the majority, if not all, of the synthase activity. The lack of consensus RNA splice sites derived from the genomic CDS1 sequence predicts that the multiple subcellular locations for synthase activities do not arise through RNA processing events.

Amino Acid Sequence↗
PubMed1996

Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus.

The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.

Administration, Oral↗