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Carbon monoxide (CO) poisoning, though with different sources, is one of the most deadly emergencies in all countries. CO can threaten men's life by several paths especially cardiac complications, which can mimic other cardiac problems such as myocardial infarction. The objective of this study was to determine ECG findings and serum troponin I levels in CO poisoned patients. In this analytical cross-sectional study, 63 CO poisoning patients were consecutively included from hospital's emergency departments. CO content was measured by a CO-oximeter and an electrocardiography was taken first thing on admission. Arterial blood gas (ABG), troponin I and other data was collected afterwards. Data were divided by age groups (adults and children) and gender. CO content was significantly higher only in subjects with normal T wave compared to patients with inverted T wave in their initial ECG (P=0.016). No other significant difference was noticed. None of the ABG findings correlated significantly with CO content. Also no significant correlation was found with CO content after stratification by gender and age groups, but pH in children (r=-0.484, P=0.026). CO content was significantly higher in adults (P=0.023), but other ABG data were not significantly different. Only 3 patients had elevated troponin I. Receiver operating characteristic (ROC) analysis showed no significant cutoff points in CO content for ECG changes. No significant specific change in electrocardiograms (ECG) could contribute carboxyhemoglobin content in carbon monoxide poisoned patients. In addition, no specific difference was found between adults and pediatric subjects' ECGs. All other findings seemed to be accidental.
BACKGROUND - Dapsone, used for Pneumocystis jiroveci (PCP) prophylaxis, is associated with increased risk of methemoglobinemia. Absence of cytochrome b5 reductase enzyme activity causes congenital methemoglobinemia, but its role in dapsone-associated methemoglobinemia is unknown. The authors sought to elucidate drug-related risk factors for dapsone-associated methemoglobinemia in pediatric oncology patients, including contribution of cytochrome b5 reductase enzyme activity.
METHODS - Among 167 pediatric patients treated for hematologic malignancies or aplastic anemia who received dapsone for PCP prophylaxis, demographic and dapsone treatment data were retrospectively collected. Drug-related risk factors were evaluated by Cox proportional hazards, and in a cross-sectional subgroup of 40 patients, cytochrome b5 reductase enzyme activity was assessed.
RESULTS - Methemoglobinemia (median methemoglobin level = 9.0% [3.5-22.4]) was documented in 32 (19.8%) patients. There was a 73% risk reduction in methemoglobinemia with dosing ≥20% below the target dose of 2 mg/kg/d (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.09-0.78; P = .016), whereas methemoglobinemia risk was increased with dosing ≥20% above the target dose (HR, 6.25; 95% CI, 2.45-15.93; P < .001). Sex, body mass index, and age were not associated with increased risk. Cytochrome b5 reductase enzyme activity did not differ by methemoglobinemia status (median 8.6 IU/g hemoglobin [Hb]; [5.5-12.1] vs 9.1 IU/g Hb; [6.7-12.7]). No patient developed PCP on dapsone.
CONCLUSIONS - Methemoglobinemia occurred in almost 20% of pediatric oncology patients receiving dapsone for PCP prophylaxis. Higher dapsone dosing is associated with increased risk. A cross-sectionally acquired cytochrome b5 reductase enzyme activity level was not associated with methemoglobinemia risk. Studies are needed to define biologic correlates of methemoglobinemia and evaluate lower dapsone doses for PCP prophylaxis.
Copyright © 2011 American Cancer Society.
Nitric oxide, when released into the bloodstream, is quickly scavenged by Hb in erythrocytes or oxidized to nitrite. Nitrite can also enter erythrocytes and oxidize Hb. The goals of this work were to determine the mechanism of erythrocyte nitrite uptake and whether this uptake causes oxidant stress in these cells. Erythrocytes took up 0.8 mM nitrite with a half-time of 11 min. Nitrite uptake was sensitive to temperature and to the pH and ionic composition of the medium but was not inhibited by the specific anion-exchange inhibitor DIDS. About 25% of nitrite uptake occurred on the sodium-dependent phosphate transporter and the rest as diffusion of nitrous acid or other species across the plasma membrane. Methemoglobin formation increased in proportion to the intracellular nitrite concentration. Nitrite reacted with erythrocyte ascorbate, but ascorbate loading of cells decreased nitrite-induced methemoglobin formation only at high nitrite concentrations. In conclusion, nitrite rapidly enters erythrocytes and reacts with oxyhemoglobin but does not exert a strong oxidant stress on these cells.
Nonenzymatic glycation of proteins by glucose leading to the formation of toxic and immunogenic advanced glycation end products (AGEs) may be a major contributor to the pathological manifestations of diabetes mellitus, aging, and, possibly, neurodegenerative diseases such as Alzheimer's. We tested the in vitro inhibition of antigenic AGE formation on bovine serum albumin, ribonuclease A, and human hemoglobin by various vitamin B1 and B6 derivatives. Among the inhibitors, pyridoxamine and thiamine pyrophosphate potently inhibited AGE formation and were more effective than aminoguanidine, suggesting that these two compounds may have novel therapeutic potential in preventing vascular complications of diabetes. An unexpected finding was that aminoguanidine inhibited the late kinetic stages of glycation much more weakly than the early phase.
Kinetic and EPR studies show that the first step in the reaction of NO with ferric myoglobin, opossum hemoglobin, and microperoxidase is the reversible formation of the H-NO complex: H + NO in equilibrium H-NO (where H = Mb+, or Hb+ OP, or MP+). The NO-combination rates are markedly affected by the presence or absence of the distal histidine. The distal histidine significantly reduces the NO-combination rates, perhaps by interaction between the distal histidine and the ferric iron. Thus the beta-chains of Hb+ OP and metmyoglobin show similar combination rates. In the absence of a distal histidine, the NO-combination rates in the alpha-chains of Hb+ OP are much faster and similar to those observed for the five-coordinate heme in microperoxidase. The loss of a water molecule from the six-coordination site is assumed to be the rate-limiting step.
The effect of pH and inositol hexaphosphate (IHP) on the symmetry of the heme environments in opossum (Didelphius marsupialis) and new Zealand White rabbit hemoglobins has been studied using electron spin resonance (ESR). Each methemoglobin is found to contain two different heme environments as detected by the rhombicity observed in the ESR spectrum. In both cases the rhombic nature of the ESR spectrum is influenced by pH and IHP binding, although in the case of rabbit methemoglobin the high spin ESR signal disappears above pH 8.0. In both hemoglobins, amino acid alterations in the alpha-chains are known to affect the properties of the ferrous derivatives. It is concluded that these alterations also provide the basis for the ESR spectral properties observed with the methemoglobins.
Opossum methemoglobin differs from methemoglobin A in spectral, spin state, conformational and chemical properties. The primary structural alterations in opossum hemoglobin, including the critical substitution at alpha 58 (E7) His leads to Gln result in the following properties. (a) Major contribution of the spectral transitions due to inositol hexakisphosphate binding arises from the alpha chains. (b) The aquomet to hydroxymet (high-spin to low-spin) transition as a function of pH is slightly retarded resulting in considerable high spin at alkaline pH. (c) The tertiary conformation (t) around the beta hemes, upon transition to a T quaternary state, differs from the known hemoglobin t tertiary structure. (d) Both alpha and beta hemes are susceptible to rapid reduction by ascorbic acid (the reduction rate being tenfold faster than that of methemoglobin A). These properties suggest that the heme environments in both the alpha and beta subunits of opossum hemoglobin are different from those of human hemoglobin A.