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B C Gladen

Publications and source records attributed to B C Gladen.

At least 19 recordsLinked to original sources
PubMed2005

Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?

Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning.

Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma and urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to due primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress.

Animals↗
PubMed2001

Risk factors for spontaneous preterm birth in two urban areas of Ukraine.

The economic, social and health problems faced by former eastern bloc countries after the demise of the Soviet Union are unique in the recent history of Europe. We conducted a study in two urban areas of Ukraine, asking if the traditional predictors of preterm delivery continue to be associated with risk under these conditions. Subjects were pregnant women with last menstrual period (LMP) between 25 December 1992 and 23 July 1994. Self-completed questionnaires and the medical record provided data. We compared 137 spontaneous preterm deliveries with 2,886 full-term births, using all established risk factors for which we had data. Maternal age was the variable most strongly related to preterm birth. Being 18 or less had an odds ratio (OR) of 3.7; being 30+ had an OR of 2.5 relative to the reference group of age 25-29. Placental complications and pre-existing hypertension had ORs of 2.7 and 2.3, respectively, but the confidence interval included 1.0. Low net pregnancy weight gain (less than 10 kg) was significantly associated with preterm birth, but the rate of net weight gain was not. Marital status and educational category were only weakly related. We conclude that although Ukraine faced serious difficulties during its transition to a market economy, these problems did not generally alter the outcome of pregnancy in our sample when the classic risk factors for preterm delivery were present.

Adolescent↗
PubMed2001

Hospital admissions during pregnancy in two urban areas of Ukraine.

Hospital admissions are generally regarded as a marker of severe pregnancy complications, and a low ratio of antenatal admissions to deliveries is considered an indicator of maternal-fetal well-being. We investigated the reasons for hospital admissions in a sample of deliveries from Ukraine, a country of the former eastern bloc. All hospitalisations were traced among 3099 women who delivered live singletons of at least 20 weeks gestation in two urban areas of Ukraine and data were abstracted from their medical records. More than a third of the women were admitted to hospital during their pregnancy, and 91% of the admissions were for a pregnancy complication, primarily threatened abortion or early labour. Median length of stay for all admissions was 12 days. The ratio of admissions to deliveries was 52 per 100. The Ukrainian ratio of hospitalisations to deliveries is notably higher than any that have been published in studies from the United States and Australia, reflecting patterns of care that stress hospital-based treatment. This high ratio does not necessarily mean that Ukrainian women are sicker, although that may be the case. The comparison of hospitalisation to delivery ratios is meaningful only when other factors, such as resources, patterns of care, costs and access, are taken into account.

Chi-Square Distribution↗
PubMed2001

An improved GC/MS-based procedure for the quantitation of the isoprostane 15-F2t-IsoP in rat plasma.

This article describes a procedure for the quantitation of the isoprostane 15-F2t-IsoP (9a,11a,15S-trihydroxy-(8b)-prosta-5Z,13E-dien-1-oic acid [CAS#27415-26-5] formerly known as 8-epi-PGF2a or 8-iso-PGF2a, and also as iPF2a-III). We have combined features from several earlier methods for 15-F2t-IsoP and prostaglandins, and identified and modified those steps that may lead to poor recoveries. The resulting protocol is precise and reliable, and was validated by a blind time-course study of plasma levels in rats treated with 120 and 1200 mg CCl4/kg body weight. Plasma levels of 15-F2t-IsoP, as measured according to the procedure described above, are good indicators of acute oxidative stress as induced by CCl4. The precision of the measurements allows detection of elevated plasma 15-F2t-IsoP levels as long as 16 h after an acute exposure of 120 mg CCl4/kg body weight, and 2 h after an exposure of 1 mg CCl4/kg body weight. The results of this low-dose, pilot study suggest that this method has sufficient analytical precision to allow the detection of the small changes in plasma isoprostane levels, which result from chronic and/or lower-level exposures to agents causing oxidative stress.

Animals↗
PubMed2000

Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc in human placentas from two cities in Ukraine.

Ukraine is a highly industrialized country with major environmental problems and deteriorating reproductive health. Heavy metals are known reproductive toxins; a study was undertaken to determine whether they were present at sufficient concentrations to be playing a major role in these health problems. Placental concentrations of arsenic, cadmium, copper, lead, mercury, and zinc were determined in 200 women from the general population of two urban areas of Ukraine, Kyiv and Dniprodzerzhinsk. Arsenic was detected in only 5% of the samples, lead in 22%, and mercury in 28%. Cadmium was detected in almost all samples, with a median of 5.2 ng/g. Concentrations of lead, mercury, and cadmium were low compared to those reported elsewhere, while zinc and copper concentrations were comparable.

Adult↗
PubMed2000

Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl(4) poisoning?

Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl(4) poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl(4) on plasma levels of alpha-tocopherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric acid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl(4) would result in losses of antioxidants from plasma. Concentrations of alpha-tocopherol and CoQ were decreased in CCl(4)-treated rats. Because of concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of alpha-tocopherol and the loss of CoQ from generalized lipid changes, due to liver damage. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes caused by liver malfunction and rupture of liver cells together with a decrease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant status of the plasma.

Animals↗
PubMed2000

Retinal degeneration in licensed pesticide applicators.

BACKGROUND: Retinal degeneration is the leading cause of visual impairment in older adults, but little is known about its relationship to neurotoxic exposures. METHODS: The Agricultural Health Study is a cohort study of licensed pesticide applicators from Iowa and North Carolina. We used cross-sectional data from self-administered questionnaires given at enrollment in 1994-1996 to compare pesticide use in 154 applicators who reported retinal degeneration and 17,804 controls. RESULTS: Retinal degeneration was associated with fungicide use (odds ratio = 1.8, 95% confidence interval = 1.3-2.6). This relationship was seen in subgroups defined by state, demographic characteristics, or medical history, as well as in the entire group. Risk increased with cumulative days of fungicide use (P for trend = 0.011) and was greater when application methods involving greater personal exposure were used. Retinal degeneration was also related to use of organochlorine or carbamate insecticides, but these associations were less consistent. Since nearly all applicators used organophosphate insecticides and herbicides, these exposures could not be effectively evaluated. CONCLUSIONS: These results suggest that exposure to some fungicides and insecticides may increase risk of retinal degeneration.

Adolescent↗
PubMed2000

Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene.

OBJECTIVES: Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal growth and development in humans. STUDY DESIGN: Follow-up of 594 children from an existing North Carolina cohort whose prenatal and lactational exposures had previously been measured. Height, weight, and stage of pubertal development were assessed through annual mail questionnaires. RESULTS: Height of boys at puberty increased with transplacental exposure to DDE, as did weight adjusted for height; adjusted means for those with the highest exposures (maternal concentration 4+ ppm fat) were 6.3 cm taller and 6.9 kg larger than those with the lowest (0 to 1 ppm). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects; neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by 5.4 kg, but differences were significant only if the analysis was restricted to white girls. CONCLUSIONS: Prenatal exposures at background levels may affect body size at puberty.

Adolescent↗
PubMed2000

Preterm birth in two urban areas of Ukraine.

OBJECTIVE: To determine whether the preterm birth rate was elevated in two urban areas of Ukraine, a former eastern bloc country that experienced serious economic, social, and health problems during its transition from a socialist republic. METHODS: We identified every pregnancy in a defined period in two urban sites where a separate study of pregnancy and childhood was being conducted. We obtained gestational age and vital status at delivery for each. Information about onset of labor and conduct of delivery was available for the subgroup enrolled in the collaborating study. RESULTS: Among 17,137 pregnancies, all but 6774 were terminated voluntarily. Among the continuing pregnancies, the preterm birth rate was 6.6% for live-born singletons of 20 or more weeks' gestation. Only 12% of preterm births involved medical intervention, the rest were idiopathic. The preterm birth rate was higher than in Europe (4.0% to 5.4%) and Canada (5.9%) but lower than for whites in the United States (8.4%). CONCLUSION: Live-born preterm birth rates are influenced by whether infants survive to be included in calculations. The high fetal mortality rate in Ukraine causes many preterm births to be excluded, thus lowering the rate. Frequent pregnancy termination and lack of ultrasound dating in Ukraine also might cause the preterm birth rate to be lower. Preterm birth rates, especially among live-born infants, are difficult to interpret and treacherous to compare across nations. Survival of the fetus and its health and development at birth are better indicators of reproductive outcome.

Female↗
PubMed2000

Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates.

Polychlorinated biphenyls (PCBs) are industrially produced environmentally persistent compounds. In developed countries all humans have detectable levels in blood and other tissues. PCBs alter thyroid hormone metabolism in animal experiments, and human data suggest background-level exposure may have similar effects in neonates. We evaluated this possible effect among 160 North Carolina children whose in utero PCB exposure was estimated on the basis of the mother's PCB levels in milk and blood, in 1978-1982 (estimated median PCB level in milk at birth, 1.8 mg/kg lipid). Their umbilical cord sera were thawed in 1998 and assayed for total thyroxine, free thyroxine, and thyroid stimulating hormone. We found that PCB exposure was not strongly related to any of the thyroid measures. For example, for a one unit change in milk PCB concentration (mg/kg lipid), the associated multivariate-adjusted increase in thyroid stimulating hormone level was 7% (95% confidence limits (CL) = -6, 21). Despite the possibility of sample degradation, these data suggest that within the range of background-level exposure in the United States, in utero PCB exposure is only slightly related to serum concentration of total thyroxine, free thyroxine, and thyroid stimulating hormone at birth.

Adult↗
PubMed2000

Polycyclic aromatic hydrocarbons in placenta.

Concentrations of chrysene, benz [a] anthracene, benzo [a]-pyrene, benzo [b] fluoranthene, indeno [1,2,3-c,d] pyrene, dibenz [a,h] anthracene, and benzo [g,h,i] perylene were measured in placentas from 200 women from two cities in Ukraine, Kyiv and Dniprodzerzhinsk. The participants had no special exposures and were chosen from among subjects in an ongoing study of reproductive health. All seven of the polycyclic aromatic hydrocarbons (PAHs) were found in all placentas, with the sole exception of benzo [a] pyrene in one placenta. Chrysene was present at the highest concentrations, with median 1.38 ng/g dry weight. Dibenz [a,h] anthracene and benzo [g,h,i] perylene had the lowest concentrations; each had median 0.73 ng/g dry weight. Concentrations in Kyiv were slightly higher than those in Dniprodzerzhinsk, but the difference was significant only for dibenz [a,h] anthracene. Dibenz [a,h] anthracene and benzo [g,h,i] perylene increased significantly with maternal body mass index, but other PAHs showed no such pattern. Placentas from deliveries in autumn or winter had slightly but not significantly higher concentrations. Concentrations were not related to maternal age. There were too few smokers in the sample for meaningful evaluation. No associations were seen between any of the placental PAH concentrations and birth weight of the infant.

Adult↗
PubMed1999

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine.

Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalent, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries.

Adult↗
PubMed1999

Correlations among polychlorinated biphenyls, dioxins, and furans in humans.

BACKGROUND: Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. METHODS: We present correlations among dioxins, furans, and PCBs in blood collected in 1991-1992 from 44 American Vietnam veterans from Michigan. RESULTS: Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher-chlorinated congeners being more highly correlated. Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated. Correlations of PCBs with dioxins and furans ranged from -0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. DISCUSSION/CONCLUSIONS: If confirmed in other populations, such correlations may allow the use of simpler assays but may also raise issues of confounding and calibration.

Adult↗
PubMed1999

Organochlorines in breast milk from two cities in Ukraine.

Reports of environmental problems in the former Soviet Union, including excess use of pesticides, have led to concerns about high levels of contamination in humans, but little information is available to assess whether these concerns are warranted. Samples of breast milk from 197 women from two cities in Ukraine were analyzed for p,p'-DDT, p,p'-DDE, endrin, dieldrin, heptachlor epoxide, trans-nonachlor, oxychlordane, hexachlorobenzene, ss-hexachlorocyclohexane (HCH), and 18 polychlorinated biphenyl congeners, and results were compared to previous reports from Europe. The median ss-HCH concentration was 731 ng/g milk fat, which is higher than other reports from Europe but lower than reports from other parts of the world. The median DDE concentration was 2,457 ng/g milk fat, which is higher than most but not all other reports from Europe. Concentrations of other chemicals were comparable to or lower than other reports from Europe. Concentrations from the city of Kyiv were generally lower than those from Dniprodzerzhinsk, but the magnitudes of these differences were modest.

Adult↗
PubMed1999

Outcomes of 17,137 pregnancies in 2 urban areas of Ukraine.

OBJECTIVES: Frequent terminations of pregnancy and high rates of fetal loss have been reported, but not confirmed, in the former eastern bloc. A census of pregnancies in Ukraine, a former eastern bloc country, was conducted to determine the rates of these events. METHODS: All pregnancies registered in 2 urban areas were enumerated. During a 19-month period between 1992 and 1994, 17,137 pregnancies and their outcomes were recorded. RESULTS: Sixty percent of the pregnancies were voluntarily terminated, generally before the 13th week. In pregnancies delivered at 20+ weeks, fetal mortality was 29 per 1000, nearly 5 times the rate among Whites in the United States. There was a greater proportion of very early deliveries (20-27 weeks) in Ukraine, as well as higher death rates at all gestational ages. Perinatal mortality was estimated to be 35 per 1000, about 3 times the US rate. CONCLUSIONS: This is believed to be the first study in the former eastern bloc to ascertain all of the clinically recognized pregnancies in a specified period and to determine their outcomes. The data document elevated reproductive risks in a former Soviet state.

Abortion, Induced↗
PubMed1998

Exposure opportunities of families of farmer pesticide applicators.

BACKGROUND: Families of farmer pesticide applicators have unusual opportunities for exposure, directly or indirectly, to pesticides. These exposures are not well characterized. METHODS: Subjects were 26,793 licensed private pesticide applicators enrolled in the Agricultural Health Study, a cohort study being conducted in Iowa and North Carolina. Questionnaires were completed by the applicators and their spouses. RESULTS: Many indirect exposure opportunities exist; for example, 21% of homes are within 50 yards of pesticide mixing areas, 27% of applicators store pesticides in their homes, and 94% of clothing worn for pesticide work is washed in the same machine as other laundry. Direct exposure opportunities also occur; for example, 51% of wives of applicators worked in the fields in the last growing season, 40% of wives have ever mixed or applied pesticides, and over half of children aged 11 or more do farm chores. DISCUSSION/CONCLUSIONS: The extent of the opportunities for exposure of family members of farmer pesticide applicators makes studies of their health important.

Adult↗