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Acta Obstetricia Et Gynecologica... Aug 2001The objective of this study was to test the hypothesis that maternal plasma, cord plasma and placental tissue lipid peroxidation products are increased and antioxidants...
BACKGROUND
The objective of this study was to test the hypothesis that maternal plasma, cord plasma and placental tissue lipid peroxidation products are increased and antioxidants are decreased in women with pre-eclampsia.
METHODS
Placenta, maternal and cord plasma were collected at delivery from 29 normal, 21 pre-eclamptic and six eclamptic women. Plasma was collected from 21 non-pregnant matched controls. The analyses were measured by HPLC and colorimetric assay.
RESULTS
Plasma maternal concentrations of uric acid, LPO, MDA, ascorbic acid, vitamin E and cholesterol were not significantly different in pre-eclampsia as compared with normal pregnancy. Plasma concentrations of ascorbic acid and vitamin E were not significantly different in normal pregnancy as compared with the non-pregnant controls. Cord plasma concentrations of MDA were significantly higher in eclampsia (1.16+/-0.26 micromol/l) as compared with normal pregnancy (0.79+/-0.05 micromol/l, p<0.02) and pre-eclampsia (0.83+/-0.05 micromol/l, p<0.05). Cord plasma concentrations of vitamin E were significantly higher in eclampsia (21.3+/-7.5 micromol/l) as compared with normal pregnancy (10.2+/-1.1 micromol/l, p<0.01) and pre-eclampsia (10.4+/-1.8 micromol/l, p<0.04). Placental concentrations of LPO, MDA and ascorbic acid were not significantly different in pre-eclampsia as compared with normal pregnancy. Plasma cord concentrations of LPO and placental concentrations of vitamin E were undetected for normal pregnant, pre-eclamptic and eclamptic women respectively. Uric acid concentrations were significantly increased in eclampsia as compared with the non-pregnant controls (p<0.0001), normal pregnant controls (p<0.0001) and pre-eclampsia (p<0.008).
CONCLUSIONS
The findings in this study do not show any evidence of deficiency in the maternal protective antioxidant systems or increased production of lipid peroxidation products, LPO and MDA in African women with pre-eclampsia as compared with normal pregnancy. However, there was evidence of increased cord plasma concentrations of MDA and vitamin E in eclampsia as compared with normal pregnancy and pre-eclampsia. The placenta may be effective in removing MDA. The antioxidant uric acid serves as a protective role whilst the antioxidant and oxidant capacity in the different study groups remained unchanged.
Topics: Adolescent; Adult; Ascorbic Acid; Black People; Case-Control Studies; Cholesterol; Eclampsia; Female; Fetal Blood; Humans; Lipid Peroxides; Malondialdehyde; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Vitamin E
PubMed: 11531614
DOI: 10.1034/j.1600-0412.2001.080008719.x -
The Journal of Clinical Endocrinology... Apr 1999Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is...
Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3'-T2 >> rT3 > T3 > T4. The apparent Km values of 3,3'-T2 and T3 [at 50 micromol/L 3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9 micromol/L for liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol, 0.14 and 29.1 micromol/L for SULT1A1, and 33 and 112 micromol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2) was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3. The sulfation of 3,3'-T2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 micromol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney.
Topics: Adult; Humans; Isoenzymes; Kinetics; Substrate Specificity; Sulfotransferases
PubMed: 10199779
DOI: 10.1210/jcem.84.4.5590 -
The American Journal of Clinical... Dec 2008Choline and betaine are linked to phospholipid and one-carbon metabolism. Blood concentrations or dietary intake of these quaternary amines have been related to the risk...
BACKGROUND
Choline and betaine are linked to phospholipid and one-carbon metabolism. Blood concentrations or dietary intake of these quaternary amines have been related to the risk of chronic diseases, including cardiovascular disease and the metabolic syndrome.
OBJECTIVE
We aimed to determine dietary predictors of plasma choline and betaine among middle-aged and elderly subjects recruited from an area without folic acid fortification.
DESIGN
This is a population-based study of 5812 men and women aged 47-49 and 71-74 y, within the Hordaland Health Study cohort. Plasma concentrations per increasing quartile of intake of foods, beverages, and nutrients were assessed by multiple linear regression analysis, and dietary patterns were assessed by factor analysis.
RESULTS
Plasma choline was predicted by egg consumption (0.16 micromol/L; P < 0.0001) and cholesterol intake (0.16 micromol/L; P < 0.0001), and betaine was predicted by consumption of high-fiber bread (0.65 micromol/L; P < 0.0001); high-fat dairy products (-0.70 micromol/L; P < 0.0001); complex carbohydrates, fiber, folate, and thiamine (0.66-1.44 micromol/L; P
CONCLUSION
In this population of middle-aged and elderly men and women, recruited from an area with relatively low folate intake, neither plasma choline nor betaine was positively associated with consumption of animal products, fruit, or vegetables, but each was positively associated with the intake of specific food items such as eggs (choline) and bread (betaine).
Topics: Aged; Betaine; Bread; Cardiovascular Diseases; Choline; Cohort Studies; Diet Surveys; Dietary Fats; Eggs; Factor Analysis, Statistical; Feeding Behavior; Female; Folic Acid; Food, Fortified; Humans; Linear Models; Male; Meat; Metabolic Syndrome; Middle Aged; Norway; Phospholipids
PubMed: 19064529
DOI: 10.3945/ajcn.2008.26531 -
The American Journal of Clinical... May 2010Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine,...
BACKGROUND
Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations.
OBJECTIVE
The objective was to examine whether choline and betaine intakes, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post-methionine-load conditions in both pre- and post-folic acid fortification periods in the United States.
DESIGN
We assessed the association between choline and betaine intakes and fasting and post-methionine-load homocysteine concentrations using the US Department of Agriculture revised food-composition tables and evaluated whether the associations varied by folic acid fortification periods in 1325 male and 1407 female participants in the sixth examination (1995-1998) of the Framingham Offspring Study.
RESULTS
A higher choline-plus-betaine intake was associated with lower concentrations of post-methionine-load homocysteine; the multivariate geometric means were 24.1 micromol/L (95% CI: 23.4, 24.9 micromol/L) in the top quintile of intake and 25.0 micromol/L (95% CI: 24.2, 25.7 micromol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 micromol/L (95% CI: 9.3, 9.9 micromol/L) in the top quintile and 10.1 micromol/L (95% CI: 9.8, 10.4 micromol/L) in the bottom quintile (P for trend < 0.001). When we stratified by plasma folate and vitamin B-12 concentrations, the inverse association was limited to participants with low plasma folate or vitamin B-12 concentrations. In the postfortification period, the inverse association between choline-plus-betaine intake and either fasting or post-methionine-load homocysteine was no longer present.
CONCLUSIONS
Choline and betaine intakes were associated with both fasting and post-methionine-load total homocysteine concentrations, especially in participants with low folate and vitamin B-12 status. The inverse association between choline and betaine intakes and homocysteine concentrations was no longer present in the postfortification period.
Topics: Betaine; Cardiovascular Diseases; Choline; Cognition Disorders; Diet; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Vitamin B 12; Vitamin B 6
PubMed: 20219967
DOI: 10.3945/ajcn.2009.28456 -
Scandinavian Journal of Work,... Aug 2004The aim of this study was to evaluate different biomarkers of exposure to N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. For this purpose, differences...
OBJECTIVES
The aim of this study was to evaluate different biomarkers of exposure to N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. For this purpose, differences in toxicokinetics between men and women and between pure and water-mixed NMP were evaluated after dermal absorption.
METHODS
Six female and six male volunteers (groups 1 and 2) were topically exposed for 6 hours to 300 mg of NMP. An additional group of six male volunteers (group 3) was exposed to 300 mg of NMP in a 50% water solution. Blood and urine were sampled before, during, and up to 9 days after the exposure. Plasma and urine were analyzed using mass spectrometry.
RESULTS
For groups 1 and 2, 16% and 18% of the applied dose were recovered in the urine as the sum of NMP and its metabolites. For group 3, 4% was recovered. The maximal concentration of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) was 10, 8.1, and 2.1 micromol/l for groups 1, 2 and 3, respectively, in plasma and 420, 360 and 62 micromol/l in urine adjusted for density. For 2-hydroxy-N-methylsuccinimide (2-HMSI), the maximal concentration was 5.4, 4.5, and 1.3 micromol/l for groups 1, 2 and 3, in plasma, respectively, and 110, 82 and 19 micromol/l in urine adjusted for density. For 5-HNMP there was a difference in time to reach the maximal concentration depending on whether pure NMP or 50% NMP in water was used. No such difference was seen for 2-HMSI. The differences in kinetics between male and female volunteers were small.
CONCLUSIONS
Preferably 2-HMSI should be used as the biomarker of exposure to NMP.
Topics: Adult; Biomarkers; Female; Humans; Male; Middle Aged; Occupational Exposure; Pyrrolidinones; Sweden
PubMed: 15458014
DOI: 10.5271/sjweh.799 -
Sheng Li Xue Bao : [Acta Physiologica... Aug 2008In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels...
In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels expressed in Xenopus oocytes and the effects of changing the channel molecular determinants characteristics on the blockade with and without ketanserin intervention using standard two-microelectrode voltage-clamp techniques. Point mutations were introduced into HERG gene (Y652A and Y652R) and subcloned into the pSP64 plasmid expression vector. Complementary RNAs for injection into oocytes were prepared with SP6 Cap-Scribe after linearization of the expression construct with EcoR I. Clampfit 9.2 software was employed for data collection and analysis. Origin 6.0 software was used to fit the data, calculate time constants and plot histograms. The results showed that ketanserin blocked WT HERG currents in voltage- and concentration-dependent manner and showed minimal tonic blockade of HERG current evaluated by the envelope of tails test. The IC50 value was (0.38+/-0.04) micromol/L for WT HERG potassium channel. The peaks of the I-V relationship for HERG channel suggested a negative shift in the voltage-dependence of activation after using ketanserin, whose midpoint of activation values (V1/2) were (-16.59+/-1.01) mV (control) vs (-20.59+/-0.87) mV (ketanserin) at 0.1 micromol/L, (-22.39+/-0.94) mV at 1 micromol/L, (-23.51+/-0.91) mV at 10 micromol/L, respectively (P<0.05, n=6). Characteristics of blockade were consistent with an open-state channel blockade, because the extent and rate of onset of blockade was voltage-dependent, increasing at more potentials even in the condition of leftward shift of activation curve. Meanwhile, in the different depolarization duration, the fractional blockade of end-pulse step current and peak tail current at 100 ms duration was significantly lower than that at 400 ms and 700 ms, which indicated that following the channel activation fractional blockade was enhanced by the activated channels. Ketanserin could also modulate the inactivation of HERG channel, which shifted the voltage-dependence of WT HERG channel inactivation curve from (-51.71+/-2.15) mV to (-80.76+/-14.98) mV (P<0.05, n=4). The S6 mutation, Y652A and Y652R, significantly attenuated the blockade by ketanserin. The IC50 value were (27.13+/-9.40) micromol/L and (20.20+/-2.80) micromol/L, respectively, increased by approximately 72-fold for Y652A and 53-fold for Y652R compared to that of WT HERG channel blockade [(0.38+/-0.04) micromol/L]. However, between the inhibitory effects of Y652A and Y652R, there was no significant difference. In conclusion, ketanserin blocks WT HERG currents in voltage- and concentration-dependent manner and preferentially blocks open-state HERG channels. Tyr-652 is one of the critical residues in the ketanserin-binding sites.
Topics: Animals; Ether-A-Go-Go Potassium Channels; Humans; Ketanserin; Mutation; Oocytes; Patch-Clamp Techniques; Potassium Channel Blockers; Xenopus
PubMed: 18690396
DOI: No ID Found -
American Journal of Physiology. Heart... Oct 2009Diastolic depolarization (DD) of atrial myocytes can lead to spontaneous action potentials (APs) and, potentially, atrial tachyarrhythmias. This study examined the...
Diastolic depolarization (DD) of atrial myocytes can lead to spontaneous action potentials (APs) and, potentially, atrial tachyarrhythmias. This study examined the hypotheses that 1) a slowly inactivating component of the Na(+) current (referred to as late I(Na)) may contribute to DD and initiate AP firing and that 2) blocking late I(Na) will reduce spontaneous and induced firing of APs by atrial myocytes. Guinea pig atrial myocytes without or with DD and spontaneous AP firing were studied using the whole cell patch-clamp technique. In experiments using cells with a stable resting membrane potential (no spontaneous DD or firing), hydrogen peroxide (H(2)O(2), 50 micromol/l) caused DD and AP firing. The H(2)O(2)-induced activity was suppressed by the late I(Na) inhibitors tetrodotoxin (TTX, 1 micromol/l) and ranolazine (5 micromol/l). In cells with DD but no spontaneous APs, the late I(Na) enhancer anemone toxin II (ATX-II, 10 nmol/l) accelerated DD and induced APs. In cells with DD and spontaneous AP firing, TTX and ranolazine (both, 1 micromol/l) significantly reduced the slope of DD by 81 +/- 12% and 75 +/- 11% and the frequency of spontaneous firing by 70 +/- 15% and 74 +/- 9%, respectively. Ramp voltage-clamp simulating DD elicited a slow inward current. TTX at 1, 3, and 10 micromol/l inhibited this current by 41 +/- 4%, 73 +/- 2%, and 91 +/- 1%, respectively, suggesting that a slowly inactivating I(Na) underlies the DD. ATX-II and H(2)O(2) increased the amplitude of this current, and the effects of ATX-II and H(2)O(2) were attenuated by ranolazine or TTX. In conclusion, late I(Na) can contribute to the DD of atrial myocytes and the inhibition of this current suppresses atrial DD and spontaneous APs.
Topics: Acetanilides; Action Potentials; Animals; Atrial Function; Cnidarian Venoms; Diastole; Female; Guinea Pigs; Heart Atria; Hydrogen Peroxide; Kinetics; Male; Myocytes, Cardiac; Patch-Clamp Techniques; Piperazines; Ranolazine; Sodium; Sodium Channel Blockers; Sodium Channels; Tachycardia, Supraventricular; Tetrodotoxin
PubMed: 19700626
DOI: 10.1152/ajpheart.00444.2009 -
The Journal of Infectious Diseases Nov 2009Hemolysis causes anemia in falciparum malaria, but its contribution to microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic...
BACKGROUND
Hemolysis causes anemia in falciparum malaria, but its contribution to microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, endothelial activation, and vascular complications. We examined the relationship of plasma hemoglobin and myoglobin to endothelial dysfunction and disease severity in malaria.
METHODS
Cell-free hemoglobin (a potent NO quencher), reactive hyperemia peripheral arterial tonometry (RH-PAT) (a measure of endothelial NO bioavailability), and measures of perfusion and endothelial activation were quantified in adults with moderately severe (n = 78) or severe (n = 49) malaria and control subjects (n = 16) from Papua, Indonesia.
RESULTS
Cell-free hemoglobin concentrations in patients with SM (median, 5.4 micromol/L; interquartile range [IQR], 3.2-7.4 micromol/L) were significantly higher than in those with moderately severe malaria (2.6 micromol/L; IQR, 1.3-4.5 micromol/L) or controls (1.2 micromol/L; IQR, 0.9-2.4 micromol/L; P < .001). Multivariable regression analysis revealed that cell-free hemoglobin remained inversely associated with RH-PAT, and in patients with SM, there was a significant longitudinal association between improvement in RH-PAT index and decreasing levels of cell-free hemoglobin (P = .047). Cell-free hemoglobin levels were also independently associated with lactate, endothelial activation, and proinflammatory cytokinemia.
CONCLUSIONS
Hemolysis in falciparum malaria results in NO quenching by cell-free hemoglobin, and may exacerbate endothelial dysfunction, adhesion receptor expression and impaired tissue perfusion. Treatments that increase NO bioavailability may have potential as adjunctive therapies in SM.
Topics: Adult; Anemia, Hemolytic; Endothelium, Vascular; Female; Hemoglobins; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Middle Aged; Myoglobin; Nitric Oxide; Severity of Illness Index; Young Adult
PubMed: 19803726
DOI: 10.1086/644641 -
Journal of Dairy Science Jun 2010The aim of this study was to determine the nucleoside and nucleotide content in ovine and caprine milks at the colostral, transitional, and mature stages of lactation.... (Comparative Study)
Comparative Study
The aim of this study was to determine the nucleoside and nucleotide content in ovine and caprine milks at the colostral, transitional, and mature stages of lactation. Samples from 18 dairy sheep and 18 dairy goats were collected at 1, 2, 3, 4, 5, and 15 d postpartum. Separation and quantitation of the 5'-nucleotides (NT) and the nucleosides (NS) was performed by reverse phase HPLC. For each compound measured, considerable interindividual variation was recorded in both species of milk. The total NS content ranged from 57 to 132 micromol/L and from 54 to 119 micromol/L in ovine and caprine milk, respectively. The major NS identified in both species of milk was uridine, representing more than 60% of the total NS pool. The mean levels of inosine and guanosine were comparable between ewe and goat milk. Instead, the mean level of cytidine across the sampling period was much higher in ewe milk (11.9 micromol/L compared with 4.5 micromol/L in goat milk) and exhibited a peak value on the fourth day of lactation. The adenosine content was at least 3-fold higher in caprine milk compared with its ovine counterpart. The total NS and orotic acid contents did not differ significantly between the 2 species. However, in the case of total NT content, interspecies differences were significant, with NT levels ranging from 294 to 441 micromol/L in ovine milk and from 166 to 366 micromol/L in caprine milk. The NT content in colostrum (1-3 d) of both species was higher than in mature milk (15 d), and uridine monophosphate was the dominant NT in all samples.
Topics: Adenosine; Adenosine Monophosphate; Animals; Cattle; Chromatography, High Pressure Liquid; Colostrum; Cytidine; Cytidine Monophosphate; Female; Goats; Guanosine; Inosine; Lactation; Milk; Nucleosides; Nucleotides; Uridine; Uridine Monophosphate
PubMed: 20494137
DOI: 10.3168/jds.2009-2836