Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

<p>Abstract</p> <p>Background</p> <p>Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia.</p> <p>Methods</p> <p>Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments.</p> <p>Results</p> <p>Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells.</p> <p>Conclusions</p> <p>We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.</p

The association between low level exposures to ambient air pollution and term low birth weight: a retrospective cohort study

BACKGROUND: Studies in areas with relatively high levels of air pollution have found some positive associations between exposures to ambient levels of air pollution and several birth outcomes including low birth weight (LBW). The purpose of this study was to examine the association between LBW among term infants and ambient air pollution, by trimester of exposure, in a region of lower level exposures. METHODS: The relationship between LBW and ambient levels of particulate matter up to 10 um in diameter (PM(10)), sulfur dioxide (SO(2)) and ground-level ozone (O(3)) was evaluated using the Nova Scotia Atlee Perinatal Database and ambient air monitoring data from the Environment Canada National Air Pollution Surveillance Network and the Nova Scotia Department of Environment. The cohort consisted of live singleton births (≥37 weeks of gestation) between January1,1988 and December31,2000. Maternal exposures to air pollution were assigned to women living within 25 km of a monitoring station at the time of birth. Air pollution was evaluated as a continuous and categorical variable (using quartile exposures) for each trimester and relative risks were estimated from logistic regression, adjusted for confounding variables. RESULTS: There were 74,284 women with a term, singleton birth during the study period and with exposure data. In the analyses unadjusted for year of birth, first trimester exposures in the highest quartile for SO(2 )and PM(10)suggested an increased risk of delivering a LBW infant (relative risk = 1.36, 95% confidence interval = 1.04 to 1.78 for SO(2 )exposure and relative risk = 1.33, 95% confidence interval = 1.02 to 1.74 for PM(10)). After adjustment for birth year, the relative risks were attenuated somewhat and not statistically significant. A dose-response relationship for SO(2 )was noted with increasing levels of exposure. No statistically significant effects were noted for ozone. CONCLUSION: Our results suggest that exposure during the first trimester to relatively low levels of some air pollutants may be associated with a reduction in birth weight in term-born infants. These findings have implications for the development of effective risk management strategies to minimize the public health impacts for pregnant women

Impacts of Exogenously Derived Nitrogen Oxide and Sulfur Compounds on the Structure and Function of the Vascular Endothelium Link Pregnancy Hypertension with Later Life Hypertension

The relationship between pregnancy hypertension and later life hypertension is explained by long-term impacts of environmental oxidants on the vascular endothelium. These impacts may precede the onset of the disease as a primary defect and may participate in the pathogenesis of hypertension itself. Continuous exposure to strong exogenous oxidants such as NOx (NO and NO2) reversibly oxidizes oxyhemoglobin (Fe2+) to methemoglobin (Fe3+), and irreversible methemoglobinemia can arise because of disruption of the oxidant/antioxidant balance supported by SO2 metabolites, as inhibitors of antioxidants, and by synergistic degradation of antioxidant thiols. Methemoglobin by itself and from heme, redox-active ferric iron as product of methemoglobin catabolism, have prooxidant properties and cause important structural and functional changes in the vascular endothelium such as growth arrest, senescence, morphological alterations and cell apoptosis. In 1975, an epidemiological study among 204 pregnant women in Labin (Croatia) identified 30 (14.7%) cases of preeclampsia and 25 (12.3%) cases of hypertension in pregnancy. Ten years later, we found a significant number of hypertension cases (N=5; P=0.0027), and among them, we found a significant number of pregnancy-induced hypertension cases (N=3; P=0.0003) and a significant number of psychoneurotic disturbances (P=0.0190), but these conditions were not found in the normotensive women ten years after giving birth (P = 0.1161). Our original findings confirm that hypertension in pregnancy is not a transient impairment but instead is an extension of the effects of exogenously induced oxidative stress on the structure and function of the vascular endothelial, and indicate delayed effects plausibly manifesting as hypertension in later life

Methemoglobinemia &#8212; A biomarker and a link to ferric iron accumulation in Alzheimer&#8217;s disease

Understanding the mechanism of oxidative stress is likely to yield new insights regarding the pathogenesis of Alzheimer\u2019s disease (AD). Our earlier work focused on the difference between hemoglobin and methemoglobin degradation, respectively leading to ferrous (Fe2+) iron, or ferric (Fe3+) iron. Methemoglobin has the role of carrier, the donor of cytotoxic and redox-active ferric (Fe3+) iron, which can directly accumulate and increase the rate of capillary endothelial cell apoptosis, and may cross into the brain parenchyma, to the astrocytes, glia, neurons, and other neuronal cells (neurovascular unit). This supposition helps us to understand the transport and neuronal accumulation process of ferric iron, and determine how iron is transported and accumulated intracellularly, identifiable as \u201cBrain rust\u201d. Earlier research found that the incidences of neonatal jaundice (p = 0.034), heart murmur (p = 0.011) and disorders such as dyslalia and learning/memory impairments (p = 0.002) were significantly higher in those children born from mothers with methemoglobinemia. Our hypothesis suggests that prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as AD and other neurodegenerative diseases