Penny Erhard

Intrauterine Exposure to Low Levels of Lead: The Status of the Neonate

It has been suggested that lead (Pb) at low exposure levels is a behavioral teratogen. Blood lead (Pb-B) was measured in 185 samples of maternal blood and in 162 samples of cord blood drawn from members of a cohort of mother-infant pairs. Routine newborn assessments, an examination for minor anomalies, the Brazelton Neonatal Behavioral Assessment (NBAS), and part of the Graham/Rosenblith Behavioral Examination (G/R) were administered. Maternal and cord Pb-B correlated 0.80. In regression analyses, Apgar scores, birthweight, length, head circumference, neonatal anomalies, and seven behavioral scales were unrelated to either maternal or cord Pb-B. Three scales--the NBAS Abnormal Reflexes, the G/R Neurological Soft Sign, and the G/R Muscle Tonus Scales--were related minimally to either cord or maternal Pb-B. Because of the contrast in maternal and cord results, despite the high correlation of maternal and cord Pb-B, the data were reanalyzed for 132 cases with paired data. Only the Soft Sign Scale remained significant and that only for cord, but not maternal Pb-B. Regression analysis revealed a suppression with the Soft Sign Scale related to the variance of the cord Pb-B that was not common with maternal Pb-B. The possibility that the fetus under stress tends to accumulate Pb was considered.

Cadmium levels in maternal blood, fetal cord blood, and placental tissues of pregnant women who smoke.

Previous studies have reported that cigarette smoking is a major source of exposure to cadmium (Cd). This study was carried out to determine the degree of exposure to Cd of pregnant women who smoke and to determine the degree of exposure to Cd of pregnant women who smoke and to determine the disposition of the Cd in the maternal-fetoplacental unit. Our data reveal that pregnant women who smoke expose themselves and their placentas to levels of Cd higher than those to which they would normally be exposed. The percentage increase in Cd due to smoking was 32% in the placenta and 59% in maternal blood; these increases are statistically significant. The mean levels of Cd in maternal blood, cord blood, and placental tissues of pregnant women who smoked were all higher than the mean levels of Cd in the same tissues and blood of pregnant women who did not smoke. In addition, the levels of Cd in the maternal blood of smokers were significantly higher than levels of Cd in the cord blood of their infants; this relationship was not found in nonsmokers. On the basis of the Cd data on cord blood and placental tissues, the fetuses found in nonsmokers. On the basis of the Cd data on cord blood and placental tissues, the fetuses of pregnant women who smoke apparently receive very little additional exposure to Cd; however, this does not lessen concern for the fetus. The presently reported increase in exposure to Cd of pregnant women due to smoking must be viewed as undesirable because Cd has been shown to alter placental function in animals, and because Cd has no known biologic function.

The effect of smoking on placental and fetal zinc status

Previous studies have reported a cadmium/zinc interaction in cadmium-exposed pregnant animals that results in (1) increased placental cadmium levels, (2) increased placental zinc levels, and (3) decreased placental zinc transport. This study was carried out to determine whether zinc status would be affected in pregnant women exposed to cadmium through cigarette smoke. Atomic absorption spectroscopy was used to determine the levels of cadmium and zinc; 65 pregnant women who smoke and 84 who do not smoke were studied. Our data reveal that increased cadmium levels in pregnant women as the result of smoking increase placental zinc levels and decrease cord red blood cell zinc levels. Significantly higher levels of both cadmium and zinc were found in the placentas of pregnant women who smoke; moreover, stepwise multiple regression showed that maternal whole blood cadmium levels predicted placental zinc levels. In regard to cord blood, a significant 9% decrease in the red blood cell zinc level was observed in infants of mothers who smoke and this decrease was correlated with smoking activity, as evaluated by measuring plasma levels of thiocyanate. Also cord red blood cell zinc levels were found to correlate with placental zinc levels in nonsmokers but not in smokers. Overall, our data show that a cadmium/zinc interaction does take place in the maternal-fetal-placental unit of pregnant women who smoke and results in less favorable zinc status in the infants.

Comparison of mercury levels in maternal blood, fetal cord blood, and placental tissues

Previous studies have reported that mercury accumulates in cord blood during pregnancy. This study was carried out to determine where in cord blood the mercury accumulates, i.e., in cord erythrocytes, in cord plasma, or in both, and to determine whether the predominant form of mercury which accumulates is methyl or inorganic mercury. From our data it is clear that methyl mercury accumulates in cord erythrocytes: A total of 30% more methyl mercury was found in fetal erythrocytes than in maternal erythrocytes. Also correlation analysis of the methyl mercury levels in maternal and fetal erythrocytes showed a strong correlation (r = 0.87). In regard to inorganic mercury, the highest concentration was found in the placenta, suggesting a barrier role, but a significant correlation (r = 0.62) was also found between the maternal and fetal plasma levels of inorganic mercury. Moreover, the inorganic mercury concentration per gram of plasma was higher in fetal cord plasma than in maternal plasma. Overall, the relative levels of methyl and inorganic mercury reported here varied considerably in materrnal and fetal erythrocytes, plasma, and in the placenta, but all of the levels were low (<6 ng Hg/gm of tissue) and in agreement with Øtotal¿ mercury levels reported by others.

Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT)

BACKGROUND Urinary markers were tested as predictors of macroalbuminuria or microalbuminuria in patients with type 1 diabetes. STUDY DESIGN Nested case-control of participants in the Diabetes Control and Complications Trial (DCCT). SETTING & PARTICIPANTS 87 cases of microalbuminuria were matched to 174 controls in a 1:2 ratio, while 4 cases were matched to 4 controls in a 1:1 ratio, resulting in 91 cases and 178 controls for microalbuminuria. 55 cases of macroalbuminuria were matched to 110 controls in a 1:2 ratio. Controls were free of micro-/macroalbuminuria when their matching case first developed micro-/macroalbuminuria. PREDICTORS Urinary N-acetyl-beta-d-glucosaminidase (NAG), pentosidine, advanced glycation end product (AGE) fluorescence, and albumin excretion rate (AER). OUTCOMES Incident microalbuminuria (2 consecutive annual AERs > 40 but < or = 300 mg/d) or macroalbuminuria (AER > 300 mg/d). MEASUREMENTS Stored urine samples from DCCT entry and 1-9 years later when macro- or microalbuminuria occurred were measured for the lysosomal enzyme NAG and the AGE pentosidine and AGE fluorescence. AER and adjustor variables were obtained from the DCCT. RESULTS Submicroalbuminuric AER levels at baseline independently predicted microalbuminuria (adjusted OR, 1.83; P < 0.001) and macroalbuminuria (adjusted OR, 1.82; P < 0.001). Baseline NAG excretion independently predicted macroalbuminuria (adjusted OR, 2.26; P < 0.001) and microalbuminuria (adjusted OR, 1.86; P < 0.001). Baseline pentosidine excretion predicted macroalbuminuria (adjusted OR, 6.89; P = 0.002). Baseline AGE fluorescence predicted microalbuminuria (adjusted OR, 1.68; P = 0.02). However, adjusted for NAG excretion, pentosidine excretion and AGE fluorescence lost the predictive association with macroalbuminuria and microalbuminuria, respectively. LIMITATIONS Use of angiotensin-converting enzyme inhibitors was not directly ascertained, although their use was proscribed during the DCCT. CONCLUSIONS Early in type 1 diabetes, repeated measurements of AER and urinary NAG excretion may identify individuals susceptible to future diabetic nephropathy. Combining the 2 markers may yield a better predictive model than either one alone. Renal tubule stress may be more severe, reflecting abnormal renal tubule processing of AGE-modified proteins, in individuals susceptible to diabetic nephropathy.

Fetal lead exposure: Antenatal factors

It was hypothesized that maternal blood lead level at delivery and cord blood lead level of the neonate would be affected by maternal use of alcohol, history of alcohol abuse, and smoking. The possibility that iron status, as reflected in maternal serum ferritin, would be related to lead level was also explored. The maternal history of alcohol abuse was unrelated to lead level in 208 samples of maternal blood and 178 samples of cord blood. However, alcohol use during pregnancy was related in a dose-response fashion to maternal and to cord blood lead level. This effect was significant with and without control of maternal smoking. The effect of maternal smoking and serum thiocyanate on maternal and cord blood lead level were also highly significant with and without control of the maternal drinking variable. Serum ferritin was marginally related to lead level for white women and for black infants, but tests of the dichotomized maternal ferritin variable did not yield a significant linkage with maternal or cord blood lead level. The results further support recommendations that women abstain from alcohol consumption and cigarette smoking in pregnancy.

AGE-RELATED CHANGES OF GLYCOSIDASES IN HUMAN RETINAL PIGMENT EPITHELIUM

This study was undertaken to determine whether there are age-related changes in the specific activities of several glycosidases in fresh retinal pigment epithelial cells (RPE) isolated from the posterior pole of human donor eyes. One hundred and twenty-one pairs of eyes from human donors, between the ages of 43 and 95 years, were obtained from the National Disease Research Interchange (NDRI, Philadelphia, PA) and the Cleveland Ohio Eye Bank within 18 to 24 h of death. None had histories of diabetes, hepatitis, HIV infection, intraocular surgery, or documented age-related macular degeneration, although several older donors with evidence of drusen were included in the study. RPE cells were isolated from the posterior third of the retina using the conventional rush method and homogenized with a glass, Broeck tissue grinder. All post-nuclear supernatants were analyzed for glycosidase activity; a smaller number of nuclear pellets were assayed to verify that the majority of the enzyme activity was associated with the post-nuclear sypernatants. Glycosidase activity was quantitated fluorometrically by measuring the enzymatic release of umbelliferone from synthetic substrate preparations, specific for each enzyme. Total protein was determined by a micro BCA protein assay. Regression analysis revealed statistically significant age-related decreases for the specific activities of alpha-mannosidase (p = 0.0001), beta-galactosidase (p = 0.0001), N-acetyl-beta-glucosaminidase (p = 0.0001), and N-acetyl beta galactosaminidase (p = 0.0001) in fresh human donor RPE cells taken from the region of the posterior third of the retina that included the macula. Mannose and N-acetyl-glucosamine are major carbohydrate monomers of the oligosaccaride chains of human rhodopsin, and a relatively high percentage of the oligosaccharide chains are galactosylated. Defects in their degradation may lead to the accumulation of undigested residual material in the RPE.

A modified lecithin/sphingomyelin ratio test for fetal maturity

Several desirable techniques (rapid chromatogram development, planimetry, acetone precipitation of lecithin, and copper molybdate staining) used in other published lecithin/sphingomyelin (L/S) ratio procedures were integrated into a single L/S ratio test. The resulting test requires only 2 ml of amniotic fluid, can be performed within 75 minutes, and is semiquantitative. Methodology tests showed a high degree of reproducibility without the need for a densitometer: Coefficients of variation for the standards and amniotic fluid samples were 11% and 4%, respectively. Also, a linear relationship was observed between the L/S weight ratios in synthetic mixtures and the corresponding area ratios up to the mature value of 2.5. Clinical evaluation on a normal and high-risk patient population showed excellent reliability: The accuracy in predicting fetal lung maturity and immaturity was 100% and 85%, respectively. Moreover, the numerical value of the L/S ratio in the immature range was found to be indicative of the severity of respiratory distress syndrome. Finally, the relationship between the L/S ratio and gestational age in a normal population was described mathematically by an approximating curve. We concluded from our methodologic and clinical data that the L/S ratio may be determined simply and reliably by means of the procedure described in this report.

Lead and δ-aminolevulinic acid dehydratase in RBC's of urban mothers and fetuses

Abstract Environmental lead pollution may pose a health hazard to the mother and her fetus, but limited information concerning this problem is available. In this study, we examined erythrocyte δ-aminolevulinic acid dehydratase (ALAD) activity and erythrocyte lead levels in urban pregnant women and fetuses. The data show that the ratio of activated/nonactivated ALAD activity and erythrocyte lead are positively correlated in both the mothers and fetuses. The mean level of ALAD inhibition was found to be 28% in the mothers and 12% in the fetuses. The data also show that fetal erythrocytes have significantly higher levels of activated ALAD activity than maternal erythrocytes, and that a positive correlation exists between maternal and fetal erythrocyte lead levels. These results indicate that “normal” urban blood lead levels inhibit erythrocyte ALAD activity in the pregnant woman and fetus.

Processing Advanced Glycation End Product‐Modified Albumin by the Renal Proximal Tubule and the Early Pathogenesis of Diabetic Nephropathy

Abstract: Diabetes is characterized by increased quantities of circulating proteins modified by advanced glycation end products (AGEs). Proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs. The proximal tubule binds, takes up, and catabolizes AGE‐modified albumin by pathways different from those of unmodified albumin. These differences were examined in polarized, electrically resistant proximal tubular cells grown in monolayer culture. In patients with type 1 diabetes, urinary excretion of a lysosomal enzyme predicted the development of nephropathy.