Heme Catabolism and Bilirubin Production in Readmitted Jaundiced Newborns.

We measured end-tidal CO levels in 50 jaundiced newborns readmitted for phototherapy at age 54-244 hours. The median end-tidal CO level was 1.55 ppm, suggesting that hemolysis is not the primary contributor to the hyperbilirubinemia in many readmitted newborns.

Acute Carbon Monoxide Poisoning Secondary to Cigarette Smoking in a 40-Year-Old Man: A Case Report.

BACKGROUND AND OBJECTIVES: Carbon monoxide is one of the most common causes of fatal intoxications in the United States, and multiple previous studies have demonstrated that cigarette smokers have higher levels of carbon monoxide in their blood. However, the potential negative effects due to acute carbon monoxide poisoning from excessive cigarette smoking have not been well established. METHODS: This is a single patient case report. RESULTS: In this case report, a 40-year-old male with a past medical history of depression, anxiety, panic attacks, and substance use disorder developed symptomatic, acute carbon monoxide poisoning secondary to heavy cigarette smoking in a confined space. In this patient, the cessation of clonazepam therapy coincided with increasing anxiety and panic disorder with agoraphobia triggering an escalation in his cigarette smoking. The patient smoked three packs of cigarettes in 3 hours and developed worsening of his symptoms. He required inpatient treatment with benzodiazepines and hyperbaric oxygen. DISCUSSION AND CONCLUSIONS: Therefore, it is important to recognize cigarette smoke as a significant source of carbon monoxide exposure. SCIENTIFIC SIGNIFICANCE: While the negative effects of cigarette smoking are often perceived as being chronic and only coming to fruition after numerous years of exposure, it is important for both physicians and patients to recognize the possibility for potentially life-threatening acute toxicity secondary to carbon monoxide exposure. (Am J Addict 2019;28:413-415).

Effects of Tai Chi exercise on blood pressure and plasma levels of nitric oxide, carbon monoxide and hydrogen sulfide in real-world patients with essential hypertension.

Objective was to investigate the effects of Tai Chi exercise on nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) levels, and blood pressure (BP) in patients with essential hypertension (EH). EH patients were assigned to the Tai Chi exercise group (HTC, n = 24), and hypertension group (HP, n = 16) by patients' willingness. Healthy volunteers matched for age and gender were recruited as control (NP, n = 16). HTC group performed Tai Chi (60 min/d, 6 d/week) for 12 weeks. Measurements (blood glucose, cholesterol, NO, CO, H2S and BP) were obtained at week 0, 6, and 12. SBP, MAP, and low-density lipoprotein cholesterol levels decreased, and high-density lipoprotein cholesterol levels increased by week 12 in the HTC group (all p < 0.05 versus baseline). Plasma NO, CO, and H2S levels in the HTC group were increased after 12 weeks (all p < 0.05 versus baseline). SBP, DBP and MAP levels were significantly lower in the HTC than in the HP group (all p < 0.05). However, no changes were observed in the HP and NP groups. Correlations were observed between changes in SBP and changes in NO, CO and H2S (r = -0.45, -0.51 and -0.46, respectively, all p < 0.05), and between changes in MAP and changes in NO, CO and H2S (r = -0.36, -0.45 and -0.42, respectively, all p < 0.05). In conclusion, Tai Chi exercise seems to have beneficial effects on BP and gaseous signaling molecules in EH patients. However, further investigation is required to understand the exact mechanisms underlying these observations, and to confirm these results in a larger cohort.

The relationship between blood lactate, carboxy-hemoglobin and clinical status in CO poisoning.

AIM: We aimed to determine the relationship between blood lactate, carboxy-hemoglobin (COHb) levels and the severity of clinical findings in patients with CO poisoning. MATERIALS AND METHODS: Patients over 18 years old and of both gender who were admitted to Emergency Department with the diagnosis of CO poisoning between 10.02.2008 and 17.03.20011 were enrolled in this study. Detailed physical examination of each patient was performed, patients and their relatives were informed about the study and written consents were noted. The levels of consciousness, physical examination findings, electrocardiographic findings, Glasgow Coma Scale (GCS) scores, laboratory results (lactate, COHb, CK-MB, Troponin-I levels) and applied treatments [normobaric oxygen therapy (NBOT), hyperbaric oxygen therapy (HBOT)] were recorded to standart data entry form for each patient. "SPSS for Windows version 18″ package program was used for statistical analysis of the data. RESULTS: Total 201 patients were included in this study. Thirty five patients (17.4%) received HBOT and lactate, COHb, CKMB, Troponin-I levels of this group were higher than the other patients. Lactate and COHb levels were statistically significantly higher in patients with GCS < 15 than the ones with GCS = 15 (p < 0.01). The patients whose both Troponin-I and CK-MB levels increased have higher lactate levels (p = 0.038), but COHb levels of these patients did not change (p = 0.495). CONCLUSIONS: According to our study, blood lactate and COHb levels were both correlated with the changes of consciousness in CO poisoning. Blood lactate levels together with COHb in defining indications for HBO treatment might be suggested.

[Urgent cesarean section in a pregnant woman with carbon monoxide poisoning]. / Sürgosségi császármetszés szén-monoxid-mérgezésben.

Recognition of carbon monoxide is difficult due to its plain physical-chemical properties. Carbon and gas operating heating systems may cause severe poisoning. Carbon-monoxide intoxication may generate severe hypoxic damage and it may cause death. The authors present the case of severe carbon monoxide poisoning affecting one young child and five adults, including a pregnant woman. Because the availability of hyperbaric oxygen therapy is limited in Hungary, urgent cesarean section was performed to avoid intrauterine hypoxic damage. The authors note that there are no standardized non-invasive methods for measuring fetal carbon-monoxide level and that the level of carbon monoxide accumulation is higher and the clearance is longer in the fetus than in the mother. The pathophysiology of carbon monoxide intoxication and therapeutic options in pregnancy are discussed.

Rapid elimination of CO through the lungs: coming full circle 100 years on.

At the start of the 20th century, CO poisoning was treated by administering a combination of CO(2) and O(2) (carbogen) to stimulate ventilation. This treatment was reported to be highly effective, even reversing the deep coma of severe CO poisoning before patients arrived at the hospital. The efficacy of carbogen in treating CO poisoning was initially attributed to the absorption of CO(2); however, it was eventually realized that the increase in pulmonary ventilation was the predominant factor accelerating clearance of CO from the blood. The inhaled CO(2) in the carbogen stimulated ventilation but prevented hypocapnia and the resulting reductions in cerebral blood flow. By then, however, carbogen treatment for CO poisoning had been abandoned in favour of hyperbaric O(2). Now, a half-century later, there is accumulating evidence that hyperbaric O(2) is not efficacious, most probably because of delays in initiating treatment. We now also know that increases in pulmonary ventilation with O(2)-enriched gas can clear CO from the blood as fast, or very nearly as fast, as hyperbaric O(2). Compared with hyperbaric O(2), the technology for accelerating pulmonary clearance of CO with hyperoxic gas is not only portable and inexpensive, but also may be far more effective because treatment can be initiated sooner. In addition, the technology can be distributed more widely, especially in developing countries where the prevalence of CO poisoning is highest. Finally, early pulmonary CO clearance does not delay or preclude any other treatment, including subsequent treatment with hyperbaric O(2).

Therapeutic potential of pegylated hemin for reactive oxygen species-related diseases via induction of heme oxygenase-1: results from a rat hepatic ischemia/reperfusion injury model.

Many diseases and pathological conditions, including ischemia/reperfusion (I/R) injury, are the consequence of the actions of reactive oxygen species (ROS). Controlling ROS generation or its level may thus hold promise as a standard therapeutic modality for ROS-related diseases. Here, we assessed heme oxygenase-1 (HO-1), which is a crucial antioxidative, antiapoptotic molecule against intracellular stresses, for its therapeutic potential via its inducer, hemin. To improve the solubility and in vivo pharmacokinetics of hemin for clinical applications, we developed a micellar hemin by conjugating it with poly(ethylene glycol) (PEG) (PEG-hemin). PEG-hemin showed higher solubility in water and significantly prolonged plasma half-life than free hemin, which resulted from its micellar nature with molecular mass of 126 kDa in aqueous media. In a rat I/R model, administration of PEG-hemin significantly elevated HO-1 expression and enzymatic activity. This induction of HO-1 led to significantly improved liver function, reduced apoptosis and thiobarbituric acid reactive substances of the liver, and decreased inflammatory cytokine production. PEG-hemin administration also markedly improved hepatic blood flow. These results suggest that PEG-hemin exerted a significant cytoprotective effect against I/R injury in rat liver by inducing HO-1 and thus seems to be a potential therapeutic for ROS-related diseases, including I/R injury.

Prevention of clinical and histological signs of proteolipid protein (PLP)-induced experimental allergic encephalomyelitis (EAE) in mice by the water-soluble carbon monoxide-releasing molecule (CORM)-A1.

We have evaluated the effects of the carbon monoxide-releasing molecule CORM-A1 [Na(2) (BH(3) CO(2) ); ALF421] on the development of relapsing-remitting experimental allergic encephalomyelitis (EAE) in SJL mice, an established model of multiple sclerosis (MS). The data show that the prolonged prophylactic administration of CORM-A1 improves the clinical and histopathological signs of EAE, as shown by a reduced cumulative score, shorter duration and a lower cumulative incidence of the disease as well as milder inflammatory infiltrations of the spinal cords. This study suggests that the use of CORM-A1 might represent a novel therapeutic strategy for the treatment of multiple sclerosis.

Environmental and occupational health risks among agricultural workers living in a rural community near petroleum refinery and motorway in Skopje region.

To assess health risks in agricultural workers associated with environmental exposure to pollutants released from a petroleum refinery and from traffic, we performed a cross-sectional study that included 119 randomly selected subjects divided in two groups. Group 1 included 60 agricultural workers living in a rural community near the petroleum refinery and a motorway overpass, whereas Group 2 consisted of 59 agricultural workers performing similar activities and living in a rural community with no exposure to industrial and traffic pollutants. Risk assessment included a questionnaire, blood pressure measurement, spirometry, laboratory tests, and toxicological analysis. The groups showed a similar prevalence of health problems, with exception of muscle pain in the extremities, headache, and fatigue, which were significantly more common in Group 1. Diastolic blood pressure was higher in Group 1, but not significantly (p=0.057). The same is true for blood carbon monoxide. Significantly higher in Group 1 were blood haemoglobin (p=0.001) and blood lead (p<0.001). Serum cholinesterase activity was similar in both groups. Our findings indicate the need of regular medical exams, ambient monitoring and environmental impact assessment in agricultural population in order to detect individuals at risk and to institute adequate preventive measures.

Effect of hyperbaric oxygen therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents.

BACKGROUND: Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure and animal experiments have shown that in rats exposed to CN intoxication, HBO can increase the concentration of CN in whole blood. OBJECTIVE: The purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment. MATERIALS AND METHODS: The patients included were those admitted to the hospital because of CO intoxication, either as fire victims with smoke inhalation injuries or from other exposures to CO. In thirty-seven of these patients we measured CN concentrations in blood samples, using a Conway/microdiffusion technique, before and after HBO. The blood samples consisted of the remaining 2 mL from the arterial blood gas analysis. CN concentration in blood from fire victims was compared to 12 patients from non-fire accidents but otherwise also exposed to CO intoxication. RESULTS: The mean WB-CN concentration before patients received HBO did not differ significantly between the two groups of patients (p = 0.42). The difference between WB-CN before and after HBO did not differ significantly between the two groups of patients (p = 0.7). Lactate in plasma before and after did not differ significantly between the two groups of patients. Twelve of the 25 fire patients and one of the non-fire patients had been given a dose of hydroxycobalamin before HBO. DISCUSSION AND CONCLUSION: CN concentrations in blood from patients admitted to hospital with CO intoxication and smoke inhalation exposure did not differ significantly from controls. Accordingly, we were not able to detect any changes in CN concentrations in blood after treatment with HBO. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00280579.

Carbon monoxide releasing molecule-2 increases the velocity of thrombus growth and strength in hemophilia A, hemophilia B and factor VII-deficient plasmas.

Carbon monoxide derived from carbon monoxide releasing molecules (CORMs) has been demonstrated to enhance normal plasma thrombus speed of growth and strength in vitro. We tested the hypothesis that tricarbonyldichlororuthenium (II) dimer (CORM-2) improves the velocity of formation and strength of hemophiliac plasma thrombi as determined by thrombelastography. Plasma deficient (<1% normal activity) in factor VIII (FVIII; n = 11 individuals), factor IX (FIX; n = 5 individuals) or factor VII (FVII; n = 4 individuals) was exposed to 0 or 100 micromol CORM-2, with coagulation initiated with tissue factor. Coagulation kinetics were monitored with thrombelastography for 15 min. Paired t-tests were used to analyze FVIII-deficient plasma results; relative change was used to describe the other plasma types tested. In FVIII-deficient plasma, CORM-2 exposure significantly (P < 0.05) increased the velocity of thrombus formation (84%) and strength (48%) compared with plasma not exposed to CORM-2. FXI-deficient clots demonstrated an increase in velocity of formation (63%) and strength (43%) after CORM-2 exposure. Lastly, CORM-2 exposure increased FVII-deficient plasma velocity of formation (45%) and strength (63%). CORM-2 markedly enhanced the velocity of clot growth and strength in hemophiliac plasma. These findings serve as the rationale to determine whether CORMs could be utilized as hemostatic agents.

Impact of protein and carbohydrate supplementation on plasma volume expansion and thermoregulatory adaptation by aerobic training in older men.

We examined whether protein-carbohydrate (CHO) supplementation immediately after exercise each day during aerobic training facilitated plasma volume (PV) expansion and thermoregulatory and cardiovascular adaptations in older men. Fourteen moderately active older men [68 +/- 5 (SD) yr] were divided into two groups so as to have no significant differences in anthropometric measures, PV, and peak oxygen consumption rate (Vo(2peak)). Each group was provided with a mixture of protein and CHO (3.2 kcal, 0.18 g protein/kg body wt, Pro-CHO, n = 7) or a non-protein and low-calorie placebo (0.5 kcal, 0 g protein/kg body wt, CNT, n = 7) immediately after cycling exercise (60-75% Vo(2peak), 60 min/day, 3 days/wk) each day for 8 wk at approximately 19 degrees C ambient temperature (T(a)) and approximately 43% relative humidity (RH). Before and after training, we measured PV, cardiac stroke volume (SV), and esophageal temperature (T(es)) during 20-min exercise at 60% of pretraining Vo(2peak) at 30 degrees C T(a) and 50% RH. Moreover, we determined the sensitivity of the chest sweat rate (DeltaSR/DeltaT(es)) and forearm vascular conductance (DeltaFVC/DeltaT(es)) in response to increased T(es) during exercise. After training, PV increased by approximately 6% in Pro-CHO (P < 0.001), with an approximately 10% increase in SV during exercise (P < 0.001), but not in CNT (P > 0.07). DeltaFVC/DeltaT(es) increased by 80% and DeltaSR/DeltaT(es) by 18% in Pro-CHO (both P < 0.01) but not in CNT (P > 0.07). Moreover, we found a significant interactive effect of group x training on PV, SV, and DeltaFVC/DeltaT(es) (all P < 0.02) but with no significant effect of group (P > 0.4), suggesting that the supplement enhanced these responses to aerobic training. Thus postexercise protein-CHO supplementation during training caused PV expansion and facilitated thermoregulatory and cardiovascular adaptations, possibly providing a new training regimen for older men.

[Forensic medical evaluation of a burn injury from combustion of flammable fluids on the human body based on morphological changes in internal organs].

The author describes morphological features of splanchnic organs in the patients that suffered an injury from combustion of flammable fluids at the body surface. The burn injury is a specific form of trauma originating from a combination of several injurious factors including thermoinhalation and intoxication with combustion products in the absence of oxygen in the centre of the hot spot. A rather specific combination of morphological changes in internal organs along with results of laboratory studies provides the most reliable criterion for forensic medical diagnosis of burn injuries from combustion of flammable fluids on the human body.

Impact of organic solvents and environmental pollutants on the physiological function in petrol filling workers.

Long term exposure to solvents and air pollutants can lead to deleterious effects on respiratory, haematological and thyroid functioning. The aim of this study was to investigate whether chronic exposure to solvents like benzene and pollutants like carbon monoxide in petrol filling workers had adverse effect on blood parameters, thyroid and respiratory functions. The study group consisted of 42 healthy, non-smoker petrol filling workers, aged 20-50 years with work (exposure) duration from 2-15 years while 36 healthy subjects of the same age group served as controls. Physical examination and measurement of pulmonary functions by portable electronic spirometer were performed. Complete blood pictures (CBP) were determined by normal haematology lab procedure and hormones by Chemiluminescence immunoassay (CLIA) light absorption techniques. There was a significant decrease in the lung volumes and capacities; the restrictive pattern was more prevalent in the workers when compared with the control groups. But in the workers exposed for long period (more than 10 years) the restrictive pattern was changed to mixed pattern. A significant increase in haemoglobin (Hb) (>16 mg %) and red blood cells (RBC) (5.4 million cells/mm3) were observed in workers with longer period of exposure when compared with the control subjects (14.483 mg% and 4.83 million cells/mm3 for Hb and RBC respectively). White blood cell count except eosinophils and platelets were significantly lower in workers compared to controls. Marked increase in the tetra iodothyroinine (T4), free thyroxine (T4F) level and significant decrease in thyroid stimulating hormones (TSH), and tri-iodothyronine (T3) were observed between long term exposed and non-exposed groups. Till now researchers focused only on the effect of solvents in workers professionally exposed to solvents without considering the effect of concomittant air pollution. The result obtained from present study indicates that there is a significant toxic effect of solvents and air pollutants on workers exposed for longer duration. Improved detection and prevention technologies are needed to answer environmentally related health questions for petrol filling workers.

Phototherapy and photo-oxidation in premature neonates.

OBJECTIVE: The potential for photo-oxidation during phototherapy in premature neonates was assessed by measuring parameters reflective of photo-oxidation. METHODS: Blood was sampled from premature neonates prior to, and after 4 and 24 h of phototherapy, respectively. Total plasma bilirubin (TPB), blood carboxyhemoglobin corrected for inspired carbon monoxide (COHbc) (a sensitive index of heme catabolism), blood thiobarbituric acid reacting substances (TBARS) (a measure of lipid peroxidation), and plasma protein carbonyls (representative of protein oxidation) were determined. Study measurements were compared with baseline values both for the entire study group, and also individually for subgroups < and > or = 1.5 kg birthweight, respectively. The percentage difference (%delta) between baseline and the 24-hour measurement was calculated for each parameter. RESULTS: Forty-one premature neonates (mean [+/- SD] gestational age 30.5 +/- 2.7 weeks and birthweight 1,499 +/- 448 g) were studied. Mean TPB values decreased from a baseline of 9.1 +/- 2.3 to one of 7.2 +/- 2.8 mg/dl, p < 0.01, during the first 24 h of phototherapy. For the entire patient sample, neither COHbc, TBARS or protein carbonyl values increased significantly over baseline measurements: COHbc: 0.90 +/- 0.26% vs. 0.92 +/- 0.32%; TBARS: 19.0 +/- 5.6 vs. 18.0 +/- 4.5 nmol/ml, and protein carbonyls 7.73 +/- 3.78 vs. 7.63 +/- 3.56 U/ml (baseline and 24-hour samples only are shown in the abstract). Similarly, for the entire group, %delta (mean, interquartile range) were not significantly different between COHbc [-3.77 (-15.89-17.65)%], TBARS [-7.47 (-17.37-7.38)%], and protein carbonyls [-1.47 (-28.51-43.48)%], respectively. For subgroup analysis of neonates < or > or = 1.5 kg birthweight, respectively, no significant increases in COHbc, TBARS or protein carbonyls were documented. A significant increase in %delta for COHbc in the <1.5 kg birthweight subgroup compared with those > or =1.5 kg, possibly indicative of hemolysis, was not matched by similar changes in %delta for TBARS or protein carbonyls, and may therefore not be a result of photo-oxidation. CONCLUSIONS: Except for changes in %delta in COHbc alone and in the smallest babies only, overall, short term phototherapy in premature infants was effective in reducing TPB concentrations without associated evidence reflective of photo-oxidation.

In utero and lactation exposure of rats to 1R4F reference cigarette mainstream smoke: effect on prenatal and postnatal development.

Childhood cognitive and behavioral deficits have been reported in children born to mothers who smoked during pregnancy (Institute of Medicine, 2001). To investigate these potential responses in an animal model, reproductive and neurotoxicity evaluations based on the U.S. FDA guidelines were used to examine the offspring of male and female Sprague-Dawley rats exposed 2 h/day, 7 days/week by nose-only inhalation to whole mainstream smoke total particulate matter (TPM). Concentrations of 150, 300, or 600 mg/m(3) were used (males: 4 weeks prior to and during mating; and females: 2 weeks prior to mating, during mating, and through weaning at postnatal day 21). Sham air controls receiving filtered air and cage controls were also maintained. F(1) rats were weighed, identified by gender, examined for clinical signs of toxicity, and evaluated for neurobehavioral effects through postnatal day 65. Parental exposure was evidenced by smoke concentration-related increases in blood carboxyhemoglobin, nicotine, and cotinine and by characteristic cigarette smoke-related rodent respiratory tract histopathology. Also, nicotine and cotinine were found in F(1) blood through the lactation period. Maternal toxicity occurred at concentrations of 300 and 600 mg TPM/m(3), where total body weight gain during gestation was significantly (p < or = 0.05) decreased compared to sham controls. While smoke concentration-related decreases in F(1) birth weight and growth were evident (600 mg TPM/m(3), significantly different from sham at all time points), no adverse effects on developmental landmarks, including age at vaginal patency or preputial separation, motor activity, acoustic startle response or learning, and memory, were observed in the F(1) generation. This study confirmed that maternal exposure to high levels of mainstream cigarette smoke during gestation and lactation reduces birth weight and retards growth in the rat neonate; however, the developmental and neurobehavioral testing methodologies employed did not appear to be sensitive for an evaluation of neonatal behavioral effects following parental smoke exposure.