Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress.

Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O(2)) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy

Eddy transport of organic carbon and nutrients from the Chukchi Shelf : impact on the upper halocline of the western Arctic Ocean

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): C05011, doi:10.1029/2006JC003899.In September 2004 a detailed physical and chemical survey was conducted on an anticyclonic, cold-core eddy located seaward of the Chukchi Shelf in the western Arctic Ocean. The eddy had a diameter of ∼16 km and was centered at a depth of ∼160 m between the 1000 and 1500 m isobaths over the continental slope. The water in the core of the eddy (total volume of 25 km3) was of Pacific origin, and contained elevated concentrations of nutrients, organic carbon, and suspended particles. The feature, which likely formed from the boundary current along the edge of the Chukchi Shelf, provides a mechanism for transport of carbon, oxygen, and nutrients directly into the upper halocline of the Canada Basin. Nutrient concentrations in the eddy core were elevated compared to waters of similar density in the deep Canada Basin: silicate (+20 μmol L−1), nitrate (+5 μmol L−1), and phosphate (+0.4 μmol L−1). Organic carbon in the eddy core was also elevated: POC (+3.8 μmol L−1) and DOC (+11 μmol L−1). From these observations, the eddy contained 1.25 × 109 moles Si, 4.5 × 108 moles NO3 −, 5.5 × 107 moles PO3 −, 1.2 × 108 moles POC, and 1.9 × 109 moles DOC, all available for transport to the interior of the Canada Basin. This suggests that such eddies likely play a significant role in maintaining the nutrient maxima observed in the upper halocline. Assuming that shelf-to-basin eddy transport is the dominant renewal mechanism for waters of the upper halocline, remineralization of the excess organic carbon transported into the interior would consume 6.70 × 1010 moles of O2, or one half the total oxygen consumption anticipated arising from all export processes impacting the upper halocline.This work was supported by the National Science Foundation, and office of Naval Research; DH OPP-0124900, NB OPP-0124868, DK OPP 0124872, RP N00014-02-1-0317

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 µm(3) vs. 1002.4±11.8 µm(3)) and in the dentate gyrus (525.9±27.2 µm(3) vs. 421.5±24.6 µm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 µm(3)) and the dentate gyrus (536.1±27.2 µm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended

Saudi-Iranian Relations Since the Fall of Saddam: Rivalry, Cooperation, and Implications for U.S. Policy

Examines how the structural, sectarian, and ideological tensions and differences over energy interests between Saudi Arabia and Iran have evolved since 2003. Analyzes the roles of the United States and Iraq and makes policy recommendations

Strong hydrographic controls on spatial and seasonal variability of dissolved organic carbon in the Chukchi Sea

A detailed analysis of dissolved organic carbon (DOC) distribution in the Western Arctic Ocean was performed during the spring and summer of 2002 and the summer of 2003. DOC concentrations were compared between the three cruises and with previously reported Arctic work. Concentrations of DOC were highest in the surface water where they also showed the highest degree of variability spatially, seasonally, and annually. Over the Canada Basin, DOC concentrations in the main water masses were: (1) surface layer (71±4 ?M, ranging from 50 to 90 ?M); (2) Bering Sea winter water (66±2 ?M, ranging from 58 to 75 ?M); (3) halocline layer (63±3 ?M, ranging from 59 to 68 ?M), (4) Atlantic layer (53±2 ?M, ranging from 48 to 57 ?M), and (5) deep Arctic layer (47±1 ?M, ranging from 45 to 50 ?M). In the upper 200 m, DOC concentrations were correlated with salinity, with higher DOC concentrations present in less-saline waters. This correlation indicates the strong influence that fluvial input from the Mackenzie and Yukon Rivers had on the DOC system in the upper layer of the Chukchi Sea and Bering Strait. Over the deep basin, there appeared to be a relationship between DOC in the upper 10 m and the degree of sea-ice melt water present. We found that sea-ice melt water dilutes the DOC signal in the surface waters, which is contrary to studies conducted in the central Arctic Ocean

Strong hydrographic controls on spatial and seasonal variability of dissolved organic carbon in the Chukchi Sea

A detailed analysis of dissolved organic carbon (DOC) distribution in the Western Arctic Ocean was performed during the spring and summer of 2002 and the summer of 2003. DOC concentrations were compared between the three cruises and with previously reported Arctic work. Concentrations of DOC were highest in the surface water where they also showed the highest degree of variability spatially, seasonally, and annually. Over the Canada Basin, DOC concentrations in the main water masses were: (1) surface layer (71±4 μM, ranging from 50 to 90 μM); (2) Bering Sea winter water (66±2 μM, ranging from 58 to 75 μM); (3) halocline layer (63±3 μM, ranging from 59 to 68 μM), (4) Atlantic layer (53±2 μM, ranging from 48 to 57 μM), and (5) deep Arctic layer (47±1 μM, ranging from 45 to 50 μM). In the upper 200 m, DOC concentrations were correlated with salinity, with higher DOC concentrations present in less-saline waters. This correlation indicates the strong influence that fluvial input from the Mackenzie and Yukon Rivers had on the DOC system in the upper layer of the Chukchi Sea and Bering Strait. Over the deep basin, there appeared to be a relationship between DOC in the upper 10 m and the degree of sea-ice melt water present. We found that sea-ice melt water dilutes the DOC signal in the surface waters, which is contrary to studies conducted in the central Arctic Ocean

Net community production in the northeastern Chukchi Sea

To assess the magnitude, distribution and fate of net community production (NCP) in the Chukchi Sea, dissolved inorganic carbon (DIC), dissolved organic carbon (DOC) and dissolved organic nitrogen (DON), and particulate organic carbon (POC) and particulate organic nitrogen (PON) were measured during the spring and summer of 2004 and compared to similar observations taken in 2002. Distinctive differences in hydrographic conditions were observed between these two years, allowing us to consider several factors that could impact NCP and carbon cycling in both the Chukchi Shelf and the adjacent Canada Basin. Between the spring and summer cruises high rates of phytoplankton production over the Chukchi shelf resulted in a significant drawdown of DIC in the mixed layer and the associated production of DOC/N and POC/N. As in 2002, the highest rates of NCP occurred over the northeastern part of the Chukchi shelf near the head of Barrow Canyon, which has historically been a hotspot for biological activity in the region. However, in 2004, rates of NCP over most of the northeastern shelf were similar and in some cases higher than rates observed in 2002. This was unexpected due to a greater influence of low-nutrient waters from the Alaskan Coastal Current in 2004, which should have suppressed rates of NCP compared to 2002. Between spring and summer of 2004, normalized concentrations of DIC in the mixed layer decreased by as much as 280 ?mol kg?1, while DOC and DON increased by ?16 and 9 ?mol kg?1, respectively. Given the decreased availability of inorganic nutrients in 2004, rates of NCP could be attributed to increased light penetration, which may have allowed phytoplankton to increase utilization of nutrients deeper in the water column. In addition, there was a rapid and extensive retreat of the ice cover in summer 2004 with warmer temperatures in the mixed layer that could have enhanced NCP. Estimates of NCP near the head of Barrow Canyon in 2004 were ?1500 mg carbon (C) m?2 d?1 which was ?400 mg C m?2 d?1 higher than the same location in 2002. Estimates of NCP over the shelf-break and deep Canada Basin were low in both years, confirming that there is little primary production in the interior of the western Arctic Ocean due to near-zero concentrations of inorganic nitrate in the mixed layer

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 µm(3) vs. 1002.4±11.8 µm(3)) and in the dentate gyrus (525.9±27.2 µm(3) vs. 421.5±24.6 µm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 µm(3)) and the dentate gyrus (536.1±27.2 µm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended

Determining net dissolved organic carbon production in the hydrographically complex western Arctic Ocean

Each spring and summer, the Chukchi Sea in the western Arctic Ocean experiences a short but intense phytoplankton bloom that is controlled by sea ice cover, nutrient availability, and river runoff. During the bloom, dissolved inorganic carbon (DIC) concentrations are drawn down in the mixed layer (shelf, ~?100 µmol kg-1; shelf-break, ~?50 µmol kg-1; basin, <?5 µmol kg-1) and converted to particulate organic carbon (POC) and dissolved organic carbon (DOC). We use ?18O and salinity to estimate DOC inputs by river and sea ice melt, allowing the marine portion of the DOC pool to be compared between seasons and to facilitate estimates of net DOC production in the region. We estimate that ~10% of the DIC consumed during net community production is converted to DOC. The remaining carbon deficit (90% of DIC drawdown) is most likely exported from the mixed layer as POC. In 2002 a carbon (C) mass balance was developed for the Chukchi Sea that showed that rates of vertical export were highest over the Chukchi Shelf near Point Barrow (64 mmol C m- d-1), but more commonly ranged from 10 to 35 mmol C m- d-1 over the remainder of the shelf. At the shelf-break and in the Canada Basin export production was <10 mmol C m- d-1. DOC plays a relatively small role as a carbon sink in the system, but quantifying its contributions provides more robust estimates of export production in the Arctic