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Background Endogenous production of carbon monoxide during hemoglobin metabolism leads to the formation of carboxyhemoglobin. Carboxyhemoglobin concentration is abnormally high in humans with hemolytic anemia (HA). Hypothesis Measurement of carboxyhemoglobin concentration can discriminate HA from other forms of anemia. Animals Twenty‐seven dogs with HA (immune‐mediated HA, n = 22; microangiopathic HA, n = 5), 27 dogs with non‐HA (kidney disease, n = 14; immune‐mediated thrombocytopenia, [n = 6]; miscellaneous, n = 7) and 24 nonanemic control dogs. Methods Prospective cohort study. Carboxyhemoglobin quantification, a CBC and biochemistry profile were performed upon admission, and survival to hospital discharge and at 30 days were the measured outcomes. Groups were compared by the Mann‐Whitney and Kruskal‐Wallis tests. Receiver‐operator characteristic (ROC) analyses were used to examine the predictive utility of carboxyhemoglobin for the diagnosis of HA in anemic dogs. Results Carboxyhemoglobin (median [interquartile range]) differed between dogs with HA (7.7% [2.5%]) and non‐HA (3.6% [1.05]; P < .001) and dogs with HA and nonanemic dogs (3.5% [0.65%]; P < .001). No difference was detected between nonHA and nonanemic dogs. The area under the ROC curve for carboxyhemoglobin as predictor of HA in anemic dogs was 0.997 (95% CI, 0.99‐1.00). Three optimal cut‐off points were identified, including 5.05%, 4.55% and 4.85%, with corresponding sensitivity/specificity of 92.6%/100%, 100%/92.6% and 96.3%/96.3%, respectively. Neither carboxyhemoglobin nor any of the CBC or chemistry analytes were associated with survival. Conclusions and Clinical Importance Carboxyhemoglobin proved an excellent predictor of HA in dogs and might constitute a useful, ancillary tool for diagnosing and monitoring hemolytic anemias.

Normally one expects that flame contact is the major cause of injury and death during fires. Analysis of the factors involved in numerous fires has revealed that most deaths were not due to flame contact, but were a consequence of the production of carbon monoxide, nitrogen oxides, and other combustion products, such as aldehydes, low molecular weight alcohols, hydrogen cyanide, and other noxious species. The major emphasis within the scope of this paper relates to the physiological and toxicological aspects of smoke produced during the combustion of materials. Special emphasis is directed toward laboratory procedures which have been developed to determine the qualitative and quantitative analysis of smoke, factors pertaining to smoke development, and to measure the response of laboratory animals exposed to smoke. The effects that fire retardants, incorporated into polymeric materials as a means of improving flammability characteristics, may have on smoke development, the mechanism of polymer degradation, and on the survival response of laboratory animals are also considered.

Background and aims: Treatment with carbon monoxide (CO) inhalation has been shown to ameliorate postoperative ileus (POI) in rodents and swine. The aim of this study was to investigate whether CO liberated from water-soluble CO-releasing molecules (CO-RMs) can protect against POI in mice and to elucidate the mechanisms involved. Methods: Ileus was induced by surgical manipulation of the small intestine (IM). Intestinal contractility–transit was evaluated by video-fluorescence imaging. Leucocyte infiltration (myeloperoxidase), inflammatory parameters (ELISA), oxidative stress (lipid peroxidation), and haem oxygenase (HO)/inducible nitric oxide synthase (iNOS) enzyme activity were measured in the intestinal mucosa and muscularis propria. Results: Intestinal contractility and transit were markedly restored when manipulated mice were pre-treated with CO-RMs. Intestinal leucocyte infiltration, expression levels of interleukin 6 (IL6), monocyte chemoattractant protein-1 and intercellular adhesion molecule-1, as well as iNOS activity were reduced by treatment with CORM-3 (a transition metal carbonyl that releases CO very rapidly); whereas expression of IL10/HO-1 was further increased when compared to nontreated manipulated mice. Moreover, treatment with CORM-3 markedly reduced oxidative stress and extracellular signal-related kinase (ERK)1/2 activation in both mucosa (early response) and muscularis (biphasic response). The p38 mitogen-activated protein kinase inhibitor SB203580 abolished CORM-3-mediated HO-1 induction. The HO inhibitor chromium mesoporphyrin only partially reversed the protective effects of CORM-3 on inflammation/oxidative stress in the muscularis, but completely abrogated CORM-3-mediated inhibition of the early “oxidative burst” in the mucosa. Conclusions: Pre-treatment with CO-RMs markedly reduced IM-induced intestinal muscularis inflammation. These protective effects are, at least in part, mediated through induction of HO-1, in a p38-dependent manner, as well as reduction of ERK1/2 activation. In addition, CORM-induced HO-1 induction reduces the early “oxidative burst” in the mucosa following IM.

Alveolar macrophages (aMs) play a central role in respiratory host defense by sensing microbial antigens and initiating immune-inflammatory responses early in the course of an infection. The purpose of this study was to investigate the effect of cigarette smoke exposure on aMs after stimulation of innate pattern recognition receptors (PRRs) in a murine model. To accomplish this, C57BL/6 mice were exposed for 8 weeks using two models of cigarette smoke exposure, nose-only or whole-body exposure, and aMs isolated from the bronchoalveolar lavage. After stimulation of aMs with pI:C, a mimic of viral replication, and bacterial cell-wall constituent LPS, aMs from cigarette smoke-exposed mice produced significantly attenuated levels of the inflammatory cytokines TNF-alpha and IL-6, and the chemokine RANTES. This attenuation was specific to the aM compartment, and not related to changes in aM viability or expression of Toll-like receptor (TLR)3 or TLR4 between groups. Furthermore, aMs from smoke-exposed mice had decreased cytokine RNA as compared with aMs from sham-exposed mice. Mechanistically, this was associated with decreased nuclear translocation of the proinflammatory transcription factor NF-kappaB, and increased activator protein-1 nuclear translocation, in aMs from smoke-exposed mice. Attenuated cytokine production was reversible after smoking cessation. Cigarette smoke exposure also attenuated TNF-alpha production after stimulation with nucleotide-oligomerization domain-like receptor agonists, showing that the effect applies more broadly to other PRR pathways. Our data demonstrate that cigarette smoke exposure attenuates aM responses after innate stimulation, including pathways typically associated with bacterial and viral infections.

Stress disturbs homeostasis and may induce various disorders. Immobilization stress (IS) induced due to reduced area provided for mobility results in the imbalance of oxidant and antioxidant status. Stress leads to male reproductive dysfunction in many species, including rodents and humans. Induction of heme oxygenase-1 (HO-1), the rate limiting enzyme in heme degradation, increases host antioxidant defenses. We elucidated the protective role of induction of HO-1 by hemin on testicular damage induced by acute IS. Male albino rats were immobilized for a period of 6 h. Hemin was given for 3 consecutive days (40 μmol/kg/day, s.c.), before subjecting the animals to acute IS. Upregulation of HO-1 following hemin administration was evidenced in our study by increasing carboxyhemoglobin (COHb) level. Histopathological evaluation confirmed that acute IS caused significant testicular tissue injury, which improves in groups pretreated with hemin. Acute IS also caused significant increases in serum catecholamines and corticosterone levels; however, it produced a significant decrease in testosterone level with non-significant changes in luteinizing hormone (LH) level. In addition, it was found that IS significantly increased testicular malondialdehyde (MDA) and decreased catalase activities. The HO-1 inducer (i.e., hemin) significantly decreased catecholamines and corticosterone levels, and increased testosterone and LH levels. Hemin also decreased testicular MDA and increased catalase activities significantly. Induction of HO-1 protects the testes through its antioxidant and anti-inflammatory effects. Thus, it represents a potential therapeutic option to protect testicular tissue from detrimental effects of IS.

Objective: To evaluate relations between production and conjugation of bilirubin in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD) deficient neonates. Methods: Term and borderline premature (35–37 weeks gestational age), healthy, male, G6PD deficient neonates were studied close to the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO (COHbc; an index of bilirubin production) and serum total conjugated bilirubin (TCB; a reflection of bilirubin conjugation) were measured in simultaneously drawn blood samples by gas chromatography and reverse phase high performance liquid chromatography respectively. A bilirubin production-conjugation index comprising COHbc/TCB was determined; a high index reflects imbalance between the bilirubin production and conjugation processes. COHbc and TCB individually and the production-conjugation index were studied in relation to serum total bilirubin (STB) concentration. Results: Fifty one G6PD deficient neonates were sampled at 51 (8) hours. COHbc values did not correlate with STB (r  =  0.22, p  =  0.15). TCB did correlate inversely with STB (r  =  −0.42, p  =  0.004), and there was a positive correlation between the production-conjugation index and STB (r  =  0.45, p  =  0.002). The production-conjugation index (median (interquartile range)) was higher in the premature (n  =  8) than term neonates (2.31 (2.12–3.08) v 1.05 (0.53–1.81), p  =  0.003). This difference was the result of changes in TCB. Conclusions: The data show that jaundice in G6PD deficient neonates is the result of an imbalance between production and conjugation of bilirubin with a tendency for inefficient bilirubin conjugation over increased haemolysis in its pathogenesis. Borderline premature infants are at especial risk of bilirubin production-conjugation imbalance.

Patients with atherosclerotic cardiovascular disease may be adversely affected by the presence of carboxyhemoglobin, even at low concentrations. We investigated the effects of carbon monoxide exposure on myocardial ischemia during exercise in 63 men with documented coronary artery disease. On each test day, subjects performed two symptom-limited incremental exercise tests on a treadmill; the tests were separated by a recovery period and 50 to 70 minutes of exposure to either room air or air containing one of two concentrations of carbon monoxide (117±4.4 ppm or 253±6.1 ppm). The order of exposure was assigned randomly. On each occasion, neither the subjects nor the study personnel knew whether the subjects had been exposed to room air or to one of the concentrations of carbon monoxide. Exposure to room air resulted in a mean carboxyhemoglobin level of 0.6 percent, exposure to the lower level of carbon monoxide resulted in a carboxyhemoglobin level of 2.0 percent, and exposure to the higher level of carbon monoxide resulted in a level of 3.9 percent. An effect of carbon monoxide on myocardial ischemia was demonstrated objectively by electrocardiographic changes during exercise. We observed a decrease of 5.1 percent (90 percent confidence interval, 1.5 to 8.7 percent; P = 0.02) and a decrease of 12.1 percent (90 percent confidence interval, 9.0 to 15.3 percent; P≤0.0001) in the length of time to a threshold ischemic ST-segment change (ST end point) after carbon monoxide exposures that produced carboxyhemoglobin levels of 2.0 percent and 3.9 percent, respectively. The length of time to the onset of angina decreased by 4.2 percent (90 percent confidence interval, 0.7 to 7.9 percent; P = 0.054) at the 2.0 percent carboxyhemoglobin level and by 7.1 percent (90 percent confidence interval, 3.1 to 10.9 percent; P = 0.004) at the 3.9 percent carboxyhemoglobin level. Significant dose–response relations were found in both the change in the length of time to the ST end point (P≤0.0001) and the change in the length of time to the onset of angina (P = 0.02). We conclude that low levels of carboxyhemoglobin exacerbate myocardial ischemia during graded exercise in subjects with coronary artery disease. (N Engl J Med 1989;321:1426–32.) CARBON monoxide is a ubiquitous and toxic air pollutant produced by the incomplete combustion of carbonaceous substances. Two major sources of carbon monoxide exposure are automotive emissions and cigarette smoke. 1 In addition, exposure to high levels of carbon monoxide can occur in numerous occupational settings. The adverse health effects of carbon monoxide are thought to be related primarily to the development of tissue hypoxia. Relatively low concentrations of carboxyhemoglobin resulting from exposure to ambient carbon monoxide are usually not associated with adverse health effects. However, patients with atherosclerotic coronary artery disease are potentially at increased risk of adverse effects because . . .

Five strains of Frankia were selected to represent a wide range of genetic diversity and examined for presence of hemoglobin. All five strains produced hemoglobin when grown on media without (–N) or with (+N) combined nitrogen. This indicates that hemoglobin is common in Frankia and is not directly associated with nitrogen fixation. Frankia strain EAN1 pec was examined in more detail. It showed greater hemoglobin concentration when grown at 2% O 2 than at 20% O 2 in the –N treatment but no effect of oxygen on hemoglobin concentration in the +N treatment. At both oxygen levels, it produced substantially more biomass in +N than in –N culture. It also produced significantly more biomass when the medium contained 0.2% CO 2 than in the absence of CO 2 . The molecular mass of the hemo- globin as determined by size exclusion chromatography was 13.4 ± 0.2 kDa (mean ± SE, n = 3) and is consistent with that of a truncated hemoglobin. The hemoglobin had absorption spectra that were typical of a hemoglobin. The oxygen dissociation rate constants for the hemoglobin were 131.2 ± 5.8 s –1 for –N culture and 166 ± 8.2 s –1 for +N culture. These rapid rates are consistent with a function in facilitated diffusion of oxygen.Key words: Frankia, hemoglobin, truncated hemoglobin.

Mean pulmonary excretion rate of carbon monoxide in 13 premature babies on ventilators was significantly higher (p less than 0.001) than that of 19 healthy infants born at full term. This correlated with carboxyhaemoglobin concentrations in blood, indicating that the premature infants on ventilators produced abnormally large amounts of bilirubin.

A 35-year-old furniture refinisher came to the occupational medicine clinic with complaints of upper respiratory irritation, fatigue, and lightheadedness occurring on a daily basis after using a methylene chloride-containing paint stripper. Determinations of blood carboxyhemoglobin (COHb) on three occasions showed an apparently linear elevation of COHb as a function of hours worked on the day of sampling. COHb levels predicted from spot industrial hygiene measurements were in close concordance with those observed in the patient, indicating the potential usefulness of COHb monitoring in estimating airborne exposure levels. Methylene chloride (or dichloromethane) is an organic solvent that has found wide use as a degreaser, paint remover, aerosol propellant, and a blowing agent for polyurethane foams, and as a solvent in food processing, photographic film production, and plastics manufacturing. Discovery of its unusual metabolic fate--conversion to carbon monoxide in vivo--has earned the compound a special place in the solvent toxicology literature. Demonstration of oncogenicity in experimental animals has occasioned a reconsideration of exposure limits, with emphasis upon stricter controls. In some workplaces, conditions prevail in which controls are inadequate to prevent even acute toxicity, much less long-term exposure risks.