Biomedical subjects

James F Brien

Publications and source records attributed to James F Brien.

At least 19 recordsLinked to original sources

PubMed2006

Imidazole-dioxolane compounds as isozyme-selective heme oxygenase inhibitors.

Several imidazole-dioxolane compounds were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds, which include (2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane (1) hydrochloride, are structurally distinct from metalloporphyrin HO inhibitors and lack the aminothiophenol moiety of azalanstat. They were found to be highly selective for the HO-1 isozyme (stress induced) and had substantially less inhibitory potency toward HO-2, the constitutive isozyme. These imidazole-dioxolane compounds are the first of their type known to exhibit this isozyme-selective HO inhibition.

Animals↗

PubMed2006

Inhibition of the enzymatic activity of heme oxygenases by azole-based antifungal drugs.

Ketoconazole (KTZ) and other azole antifungal agents are known to have a variety of actions beyond the inhibition of sterol synthesis in fungi. These drugs share structural features with a series of novel heme oxygenase (HO) inhibitors designed in our laboratory. Accordingly, we hypothesized that therapeutically used azole-based antifungal drugs are effective HO inhibitors. Using gas chromatography to quantify carbon monoxide formation in vitro and in vivo, we have shown that azole-containing antifungal drugs are potent HO inhibitors. Terconazole, sulconazole, and KTZ were the most potent drugs with IC(50) values of 0.41 +/- 0.01, 1.1 +/- 0.4, and 0.3 +/- 0.1 microM for rat spleen microsomal HO activity, respectively. Kinetic characterization revealed that KTZ was a noncompetitive HO inhibitor. In the presence of KTZ (2.5 and 10 microM), K(m) values for both rat spleen and brain microsomal HO were not altered; however, a significant decrease in the catalytic capacity (V(max)) was observed (P < 0.005). KTZ was also found to weakly inhibit nitric-oxide synthase with an IC(50) of 177 +/- 2 microM but had no effect on the enzymatic activity of NADPH cytochrome P450 reductase. Because these drugs were effective within the concentration range observed in humans, it is possible that inhibition of HO may play a role in some of the pharmacological actions of these antimycotic drugs.

Animals↗

PubMed2006

Spatial learning deficits induced by chronic prenatal ethanol exposure can be overcome by non-spatial pre-training.

UNLABELLED: This study tested the hypothesis that behavioural intervention, in the form of non-spatial pre-training, mitigates the deficits in spatial learning tasks induced in guinea pig offspring by chronic prenatal ethanol exposure (CPEE). Timed, pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding, or water throughout gestation. Offspring received non-spatial pre-training, in which animals were exposed to the procedural requirements of the water maze in the absence of distal spatial cues, and then were tested in both stationary-platform and moving-platform tasks with spatial cues. Saliva cortisol was quantified in non-trained and pre-trained animals before and after exposure to the water maze. RESULTS: CPEE offspring exhibited performance deficits in the stationary-platform task, and non-spatial pre-training improved performance of CPEE offspring to control levels. In contrast, non-spatial pre-training had no effect on the impaired performance of CPEE offspring in the moving-platform task. Non-trained CPEE offspring had elevated saliva cortisol concentration after water-maze exposure compared to control offspring. Moreover, pre-trained control animals exhibited a sensitization of the cortisol response after repeated exposure to the water maze, and this was not evident in pre-trained CPEE offspring. CONCLUSIONS: These data demonstrate that CPEE produced deficits in spatial learning and memory processes that were partially overcome by non-spatial pre-training; however, more difficult tasks continued to reveal cognitive deficits. For repeated exposure to the water maze, CPEE offspring achieved a level of performance that was not different from control offspring, suggesting that it is the initial rate of acquisition of new learning, rather than the overall ability to learn, that is most adversely affected by CPEE.

Animals↗

PubMed2006

Selectivity of imidazole-dioxolane compounds for in vitro inhibition of microsomal haem oxygenase isoforms.

Haem oxygenases (HO) are involved in the catalytic breakdown of haem to generate carbon monoxide (CO), iron and biliverdin. It is widely accepted that products of haem catabolism are involved in biological signaling in many physiological processes. Conclusions to most studies in this field have gained support from the judicious use of synthetic metalloporphyrins such as chromium mesoporphyrin (CrMP) to selectively inhibit HO. However, metalloporphyrins have also been found to inhibit other haem-dependent enzymes, such as nitric oxide synthase (NOS), cytochromes P-450 (CYPs) and soluble guanylyl cyclase (sGC), induce the expression of HO-1 or exhibit varied toxic effects. To obviate some of these problems, we have been examining non-porphyrin HO inhibitors and the present study describes imidazole-dioxolane compounds with high selectivity for inhibition of HO-1 (rat spleen microsomes) compared to HO-2 (rat brain microsomes) in vitro. (2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane hydrochloride) was identified as the most selective inhibitor with a concentration of 0.6 microM inhibiting HO-1(inducible) by 50% compared with 394 microM for HO-2 (constitutive). These compounds were found to have no effects on the catalytic activities of rat brain NOS and lung sGC, but were potent inhibitors of microsomal CYP2E1 and CYP3A1/3A2 activities. In conclusion, we have identified imidazole-dioxolanes that are able to inhibit microsomal HO in vitro with high selectivity for HO-1 compared to HO-2, and little or no effect on the activities of neuronal NOS and sGC. These molecules could be used to facilitate studies on the elucidation of physiological roles of HO/CO in biological systems.

Animals↗

PubMed2006

Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal Guinea pig.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n=8), isocaloric-sucrose/pair-feeding (n=8) or water (n=2) throughout gestation. At gestational day 65 (term, gestational day 66 to 69), each dam and her offspring were euthanized, and meconium was collected from the term fetal large intestine. Eight individual FAEE (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic and arachidonic AEE) were measured by gas chromatography--flame ionization detection and confirmed by gas chromatography--mass spectrometry. The chronic maternal ethanol regimen decreased fetal body weight and brain weight. There was virtually no measurable FAEE in the meconium for the water group (n=3 fetuses). For meconium of the ethanol offspring (n=25 fetuses) compared with the sucrose offspring (n=23 fetuses), the total FAEE concentration was 8-fold higher; and lauric, palmitic, stearic and oleic AEE concentrations were at least 5-fold higher for the ethanol group. The data indicate that fetal meconium FAEE constitute a biomarker of prenatal ethanol exposure for a maternal ethanol regimen that restricts fetal development, with an inverse relationship between meconium total FAEE concentration and both body weight and brain weight.

Animals↗

PubMed2005

Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors.

Several analogues based on the lead structure of azalanstat were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). A number of these compounds, which are structurally distinct from metalloporphyrin HO inhibitors, were found to be selective for the HO-1 isozyme (stress induced), and had substantially less inhibitory activity on HO-2, the constitutive isozyme.

Aniline Compounds↗

PubMed2005

A Guinea pig model for the identification of in utero alcohol exposure using fatty acid ethyl esters in neonatal hair.

Measuring levels of fatty acid ethyl esters (FAEE) in hair has been a useful way to discriminate between adult heavy and nondrinkers. Extending the use of FAEE into neonatal hair to objectively identify children exposed to alcohol in utero may revolutionize current methods used to diagnose fetal alcohol spectrum disorder (FASD). Here we confirm for the first time that chronic exposure to alcohol during pregnancy in guinea pigs leads to increased levels of FAEE in both maternal and neonatal hair. The mean cumulative FAEE concentration in exposed maternal samples taken at GD57 was 0.431+/-0.140 pmol/mg (mean+/-SEM); levels observed in corresponding sucrose and water controls were 10-fold lower. Similarly, FAEE concentrations in exposed offspring samples taken at postnatal d 1 (mean cumulative FAEE=0.491+/-0.177 pmol/mg) were more than 15-fold higher than control counterparts. Sixty percent of all alcohol-exposed animal samples contained two or more quantifiable FAEE, whereas close to 90% of either water or sucrose control samples did not have more than one quantifiable level of a single FAEE. Results of this study suggest that FAEE in neonatal hair may be useful biomarkers in identifying in utero alcohol exposure and may facilitate the early diagnosis and treatment of FASD.

Animals↗

PubMed2004

Elimination kinetics of ethanol in pregnant women.

To evaluate the pharmacokinetics of ethanol in the early second trimester of pregnancy, ethanol concentrations simultaneously measured in the maternal blood (EtOH-MB) and in the amniotic fluid (EtOH-AF) of six pregnant women were obtained from a previous study in which a single ethanol dose of 300mgkg(-1) body weight was administered orally. For maternal blood ethanol concentration, the kinetic equation was: [Formula: see text] where k(12) and k(21) are, respectively, the rate constant of ethanol transfer from either the central compartment to the peripheral compartment or vice versa; V(max)(EtOH)is the maximal velocity for ethanol oxidation; and K(m)(EtOH) is the concentration at which half of the maximal rate of ethanol elimination is reached. The maximum concentration of EtOH in AF was 60% lower than in MB (P=0.36). However, the AUC(0-3.5h) in AF was only 16% lower than the value for MB (P=0.059). The k(12) (0.20 =/- 0.26 h(-1)) was almost twice faster than k(21) (0, h(-1)). The V(max)(EtOH) was 237.6 +/- 71.5 microgml(-1)h(-1) and K(m)(EtOH) was 3.7 +/- 4.7 microgml(-1). Our results imply that in the early second trimester, ethanol metabolism is fast. However, ethanol clearance from the AF is slower than ethanol clearance in MB. This process is widely variable, and our findings may partially explain the wide variability of ethanol's toxic effects on the fetus.

Acetaldehyde↗

PubMed2004

The source of heme for vascular heme oxygenase I: heme uptake in rat aorta.

During the last decade, heme oxygenase (HO) and carbon monoxide (CO) have garnered substantial research interest in terms of cell and organ regulation, especially as they bear on the central nervous system, organ transplantation, and the cardiovascular system. While the enzymatic mechanism, substrates, and products of HO are well known, it is not clear whether the cardiovascular system derives its supply of the heme substrate through de novo synthesis or uptake from the extracellular milieu. The objective of the present study was to test the latter possibility in rat aorta and to determine the influence of plasma proteins that bind heme in vivo, viz. hemopexin and albumin. Aortic tissue was exposed to [14C]heme in vitro, and the concentration and time dependence of heme uptake was assessed. The presence of hemopexin or albumin in the incubation medium dramatically decreased heme uptake by the aorta. Heme uptake by aortic tissue was not altered after induction of HO-1, which would be expected to increase tissue heme demand. In summary, the rat, isolated aorta was capable of obtaining heme from its external milieu, but this was obtunded in the presence of the plasma proteins hemopexin or albumin. For normal physiological situations, heme uptake may not be a usual source of substrate for vascular HO and hemoenzymes such as nitric oxide synthase, soluble guanylyl cyclase, and cyclooxygenase.

Animals↗

PubMed2004

The source of heme for vascular heme oxygenase II: de novo heme biosynthesis in rat aorta.

Heme is an essential prosthetic group or substrate for many proteins, including hemoglobin, and hemo enzymes such as nitric oxide synthase, soluble guanylyl cyclase, and heme oxygenase (HO). HO is responsible for the breakdown of heme into equimolar amounts of biliverdin, iron, and carbon monoxide, the latter of which is thought to play a role in the regulation of vascular tone. It is not clear whether the source of heme for cardiovascular functions is derived from uptake from the extracellular milieu or synthesis. In this study, we tested the hypothesis that blood vessels obtain their supply of heme for HO through de novo synthesis. Adult male Sprague-Dawley rat aorta was incubated at 37 degrees C in Krebs' solution with 1 micro M [14C]delta-aminolevulinic acid (ALA). [14C]ALA uptake was linear for about 30 min and reached a plateau at approximately 100 min. The radioactivity was incorporated into porphyrins and heme as determined by esterification of 14C-labelled metabolites and thin-layer chromatography. The first and rate-limiting step of heme biosynthesis is catalyzed by ALA synthase (ALA-S), the activity of which was determined in rat aorta using a radiometric assay, approximately 250 nmol x (g wet mass)(-1) x h(-1). Inducing HO-1 in rat aorta with S-nitroso-N-acetylpenicillamine (500 micro M) did not increase ALA-S activity as compared with basal activity levels of the enzyme. It appears that there is a sufficient amount of heme available under basal ALA-S activity conditions to meet the increased demand for heme resulting from HO-1 induction. These observations indicate that the complete enzymatic pathway for de novo heme biosynthesis resides in rat aorta and furthermore indicate that de novo heme synthesis is capable of supplying a substantial portion of the heme substrate for HO in the aorta.

5-Aminolevulinate Synthetase↗

PubMed2003

Differential effects of pirfenidone on acute pulmonary injury and ensuing fibrosis in the hamster model of amiodarone-induced pulmonary toxicity.

Pulmonary toxicity, including fibrosis, is a serious adverse effect associated with the antidysrhythmic drug amiodarone (AM). We tested the potential usefulness of pirfenidone against AM-induced pulmonary toxicity in the hamster model. Intratracheal AM administration resulted in pulmonary fibrosis 21 days posttreatment, as evidenced by an increased hydroxyproline content and histological damage. Dietary pirfenidone administration (0.5% w/w in chow), for 3 days prior to and continuously after AM, prevented fibrosis and suppressed elevation of pulmonary transforming growth factor (TGF)-beta1 mRNA content at 7 and 21 days post-AM. Protection against AM-induced lung damage was not observed when supplementation with pirfenidone was delayed until 7 days following AM administration, suggesting that alteration of early events in AM lung toxicity is necessary for the protective effect of pirfenidone. Both AM and bleomycin, another pulmonary fibrogen, caused inflammation 24 h after intratracheal dosing, measured as increased lactate dehydrogenase activity, protein content, and cellular alterations in bronchoalveolar lavage fluid, with the response to AM markedly greater than that to bleomycin. Administration of AM, but not bleomycin, also caused whole lung mitochondrial dysfunction, alveolar macrophage death, and an influx of eosinophils into the lung, of which pirfenidone was able to decrease only the latter. We conclude that: (1) AM induces alveolar macrophage death and severe, acute pulmonary inflammation with associated eosinophilia following intratracheal administration; (2) mitochondrial dysfunction may play an early role in AM pulmonary injury; and (3) pirfenidone decreases AM-induced pulmonary fibrosis in the hamster, probably through suppression of TGF-beta1 gene expression.

Acute Disease↗

PubMed2003

Effects of chronic prenatal ethanol exposure on NMDA receptor number and affinity for [3H]MK-801 in the cerebral cortex of the young postnatal and adult guinea-pig.

The objective of this study was to test the hypothesis that chronic prenatal ethanol exposure (CPEE) produces changes in the number and/or affinity of N-methyl-D-aspartate (NMDA) receptors in the cerebral cortex that are developmental-age-dependent. Timed, pregnant Dunkin-Hartley-strain guinea-pigs received oral intubation of one of the following regimens, given daily as two equally divided doses 2 h apart, from gestational day (GD) 2 to GD 67 (term, ~GD 68): (i) 4 g ethanol kg(-1) maternal bodyweight; (ii) isocaloric sucrose with pair feeding; or (iii) water. Maternal blood ethanol concentration was measured on GD 57 or 58 at 1 h after the daily dose, and was 51.1 +/- 8.5 mM (235 +/- 39 mg dL(-1); n = 8). At postnatal day (PD) 11 (pre-weaning) and PD 61 (adulthood), body, brain and cerebral cortical weights of the offspring were measured. The number of NMDA receptors and their affinity for [(3)H]MK-801 were measured in a crude cerebral cortical membrane preparation using saturation isotherm analysis to determine the B(max) and K(D). Chronic prenatal ethanol exposure decreased offspring brain and cerebral cortical weights at PD 11 and PD 61. At PD 11, there was no CPEE-induced change of [(3)H]MK-801 binding characteristics in the cerebral cortex. At PD 61, both B(max) and K(D) for [(3)H]MK-801 binding to cerebral cortical NMDA receptors were decreased by CPEE compared with the isocaloric sucrose/pair-fed and water treatment groups. Loss of cerebral cortical NMDA receptors and increased affinity of the remaining receptors for [(3)H]MK-801 in the adult guinea-pig, compared with no change in the number or affinity of these receptors in the young postnatal offspring, demonstrated that the effects of CPEE on these ionotropic glutamate receptors are developmental-age-dependent.

Animals↗

PubMed2003

Chronic prenatal ethanol exposure alters ionotropic glutamate receptor subunit protein levels in the adult guinea pig cerebral cortex.

BACKGROUND: The superfamily of glutamate-gated ion channels mediates fast excitatory synaptic transmission in the central nervous system and is composed of the NMDA, AMPA, and kainate receptors. Binding studies have shown that chronic prenatal and/or neonatal ethanol exposure produces persistent effects on the numbers of some of these channels. However, whether or not this chronic ethanol exposure produces long-lasting effects on the expression of specific ionotropic receptor subunits remains an open question. METHODS: Timed pregnant Dunkin-Hartley strain guinea pigs received oral administration of one of the following regimens between gestational days 2 and 67: (1) 4 g of ethanol per kilogram of maternal body weight per day with ad libitum access to pellet food and water (ethanol group), (2) isocaloric sucrose- and pair-feeding with ad libitum access to water (sucrose group), or (3) isovolumetric water with ad libitum access to food and water (water group). The maternal blood ethanol concentration produced by the ethanol regimen was 71 +/- 12 mM. Adult offspring were killed on postnatal day 61, and cerebral cortical tissue was analyzed for ionotropic glutamate receptor subunit expression by Western immunoblotting. RESULTS: There was a statistically significant decrease in NR2B subunit protein expression and an increase in GluR2/3 subunit protein expression in the ethanol group. Expression of NR1, NR2A, NR2C, GluR1, GluR6/7, and KA2 subunit proteins was not affected. CONCLUSIONS: These results demonstrate that chronic prenatal ethanol exposure produces long-lasting effects on the subunit composition of NMDA and AMPA receptors in the cerebral cortex of the adult guinea pig.

Animals↗

PubMed2003

Attenuation of amiodarone-induced pulmonary fibrosis by vitamin E is associated with suppression of transforming growth factor-beta1 gene expression but not prevention of mitochondrial dysfunction.

Amiodarone (AM) is an efficacious antidysrhythmic agent that can cause numerous adverse effects, including potentially life-threatening pulmonary fibrosis. The current study was undertaken to investigate potential protective mechanisms of vitamin E against AM-induced pulmonary toxicity (AIPT) in the hamster. Three weeks after intratracheal administration of AM (1.83 micromol), increased pulmonary hydroxyproline content and histological damage were observed, indicative of fibrosis. These effects were preceded by increased pulmonary levels of transforming growth factor (TGF)-beta1 mRNA at 1 week post-AM, which remained elevated 3 weeks post-AM. Dietary supplementation with vitamin E resulted in rapid pulmonary accumulation of the vitamin, and prevention of AM-induced increases in TGF-beta1, hydroxyproline, and histological damage. Although dietary supplementation also markedly elevated lung mitochondrial vitamin E content, it did not attenuate AM-induced inhibition of mitochondrial respiration or disruption of mitochondrial membrane potential in vitro, or lung mitochondrial respiratory inhibition resulting from in vivo AM administration. These results suggest that vitamin E reduces the extent of pulmonary damage after AM administration via down-regulating TGF-beta1 overexpression but that it does not modify AM-induced mitochondrial dysfunction, a potential initiating event in AIPT.

Amiodarone↗

PubMed2003

Chronic prenatal ethanol exposure-induced decrease of guinea pig hippocampal CA1 pyramidal cell and cerebellar Purkinje cell density.

The brain is a key target of ethanol teratogenicity, in which ethanol can produce neurodegeneration in selected areas, including the hippocampus and cerebellum. The research objective was to test the hypothesis that chronic prenatal ethanol exposure, via maternal ethanol administration, produces differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells. Timed pregnant guinea pigs received chronic oral administration of ethanol, isocaloric-sucrose/pair-feeding, or water throughout gestation (term, about gestational day (GD) 68), and the offspring were studied at GD 62 (near-term fetus), postnatal day (PD) 1 (neonate), PD 5, and PD 12 (early postnatal life). Ethanol treatment, compared with isocaloric-sucrose/pair-feeding and water treatments, decreased brain, hippocampal, and cerebellar weights at GD 62, PD 1, PD 5, and PD 12. Hippocampal CA1 pyramidal cell linear density and cerebellar Purkinje cell linear density were unaffected at GD 62. Ethanol treatment produced 25, 30, and 30% decreases in linear density of hippocampal CA1 pyramidal cells at PD 1, PD 5, and PD 12, respectively, and a 30% decrease in linear density of cerebellar Purkinje cells at PD 12 only. At PD 5, Purkinje cell profile linear density remained unaffected; however, ethanol treatment appeared to increase linear density of apoptotic Purkinje cell nuclei, as determined by a modified TUNEL method. The data demonstrate that chronic prenatal ethanol exposure produces apparent differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells in the developing guinea pig.

Administration, Oral↗

PubMed2003

Heme oxygenase expression in selected regions of term human placenta.

Carbon monoxide (CO), formed during heme oxygenase (HO)-catalyzed oxidation of heme, has been proposed to play a complementary role with nitric oxide in the regulation of placental hemodynamics. The objective of this study was to elucidate HO enzymatic activity and HO-1 (inducible) and HO-2 (constitutive) protein content in the microsomal subcellular fraction of homogenate of selected regions of placenta from normotensive and mild pre-eclamptic pregnancies. HO enzymatic activity was measured under optimized conditions by gas chromatography using CO formation as an index of activity, and HO-1 and HO-2 protein content were determined by Western immunoblot analysis. Microsomal HO activity in each of the four placental regions was not different between normotensive and mild pre-eclamptic pregnancies. Microsomal HO-2 protein content was not different between normotensive and mild pre-eclamptic pregnancies, whereas there was increased expression of microsomal HO-1 protein in chorionic villi and fetal membranes from pre-eclamptic pregnancy compared with normotensive pregnancy. Microsomal HO enzymatic activity correlated with HO-2, but not HO-1, protein content.

Cell Fractionation↗

PubMed2002

Measurement of endogenous carbon monoxide formation in biological systems.

Endogenous carbon monoxide (CO) formation has been measured in different biological systems using a variety of analytical procedures. The methods include gas chromatography-reduction gas detection, gas chromatography-mass spectroscopic detection, laser sensor-infrared absorption, UV-visible spectrophotometric measurement of CO-hemoglobin or CO-myoglobin complex, and formation of (14)CO from (14)C-heme formed following [2-(14)C]glycine administration. CO formation ranged from a low of 0.029 nmol/mg of protein/h in chorionic villi of term human placenta to a high of 0.28 nmol/mg of protein/h in rat olfactory receptor neurons in culture and rat liver perfusate.

Animals↗

PubMed2002

Heme oxygenase activity in placenta: direct dependence on oxygen availability.

Carbon monoxide (CO), which is formed endogenously from heme catalyzed by heme oxygenase (HO), is proposed to play a role in vascular control. The mRNA and protein expression of the inducible isoform of HO (HO-1) increases in response to hypoxia, and it has been assumed that HO activity also increases. This assumption requires evaluation because the catalytic activity of HO requires three molecules of O(2) for each molecule of CO formed from heme, and HO activity may be limited by O(2) availability. To test the hypothesis that low physiological O(2) concentrations limit HO activity, heme-derived CO formation by microsomal fractions of homogenates of chorionic villi of human placentas was determined after exposure to 0, 1, 5, or 21% O(2). Results revealed that HO activity was directly dependent on O(2) concentration. Thus, although hypoxia may increase HO protein and mRNA expression, there is a progressive decrease in HO activity with decreasing O(2) concentration and the dependence of HO activity on O(2) concentration is similar in chorionic villi from noninfarcted areas of preeclamptic and normotensive placenta.

Carbon Monoxide↗