Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Circulating and tissue biomarkers as predictors of bromine gas inhalation.

The threat from deliberate or accidental exposure to halogen gases is increasing, as is their industrial applications and use as chemical warfare agents. Biomarkers that can identify halogen exposure, diagnose victims of exposure or predict injury severity, and enable appropriate treatment are lacking. We conducted these studies to determine and validate biomarkers of bromine (Br2 ) toxicity and correlate the symptoms and the extent of cardiopulmonary injuries. Unanesthetized rats were exposed to Br2 and monitored noninvasively for clinical scores and pulse oximetry. Animals were euthanized and grouped at various time intervals to assess brominated fatty acid (BFA) content in the plasma, lung, and heart using mass spectrometry. Bronchoalveolar lavage fluid (BALF) protein content was used to assess pulmonary injury. Cardiac troponin I (cTnI) was assessed in the plasma to evaluate cardiac injury. The blood, lung, and cardiac tissue BFA content significantly correlated with the clinical scores, tissue oxygenation, heart rate, and cardiopulmonary injury parameters. Total (free + esterified) bromostearic acid levels correlated with lung injury, as indicated by BALF protein content, and free bromostearic acid levels correlated with plasma cTnI levels. Thus, BFAs and cardiac injury biomarkers can identify Br2 exposure and predict the severity of organ damage.

Determinants of plasma PCB, brominated flame retardants, and organochlorine pesticides in pregnant women and 3 year old children in The Norwegian Mother and Child Cohort Study.

BACKGROUND: Exposure to persistent organic pollutants (POPs) during prenatal and postnatal life has been extensively studied in relation to adverse health effects in children. OBJECTIVES: The aim was to identify determinants of the concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (polybrominated diphenyl ethers, PBDEs; polybrominated biphenyl, PBB), and organochlorine pesticides (OCPs) in blood samples from pregnant women and children in The Norwegian Mother and Child Cohort Study (MoBa). METHODS: Blood samples were collected from two independent subsamples within MoBa; a group of women (n=96) enrolled in mid-pregnancy during the years 2002-2008 and a group of 3 year old children (n=99) participating during 2010-2011. PCB congeners (74, 99, 138, 153, 180, 170, 194, 209, 105, 114, 118, 156, 157, 167, and 189), brominated flame retardants (PBDE-28, 47, 99, 100, 153, 154, and PBB-153), as well as the OCPs hexachlorobenzene (HCB), oxychlordane, 4,4'dichlorodiphenyltrichloroethane (DDT), and 4,4'dichlorodiphenyldichloroethylene (DDE) were measured in both pregnant women and children. RESULTS: Age, low parity, and low pre-pregnant BMI were the most important determinants of increased plasma concentrations of POPs in pregnant women. In 3 year old children, prolonged breastfeeding duration was a major determinant of increased POP concentrations. Estimated dietary exposure to PCBs during pregnancy was positively associated with plasma concentrations in 3 year old children, but not in pregnant women. Plasma concentrations were approximately 40% higher in children compared to pregnant women. CONCLUSIONS: Several factors associated with exposure and toxicokinetics, i.e. accumulation, excretion and transfer via breastmilk of POPs were the main predictors of POP levels in pregnant women and children. Diet, which is the main exposure source for these compounds in the general population, was found to predict PCB levels only among children. For the PBDEs, for which non-dietary sources are more important, toxicokinetic factors appeared to have less predictive impact.

Persistent organic pollutants including polychlorinated and polybrominated dibenzo-p-dioxins and dibenzofurans in firefighters from Northern California.

Polychlorinated and polybrominated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs and PBDD/Fs) were measured in serum of twelve firefighters sampled after a fire event in San Francisco, California, along with polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), p,p'-DDE, hexachlorobenzene (HCB), perfluorinated chemicals (PFCs), bisphenol-A (BPA) and tetrabromobisphenol-A (TBBPA). TEQPCDD/F concentrations were relatively low (mean 5pgg(-1) (lipid weight), lw, range 1-11pgg(-1)lw), but concentrations of 1,2,3,4,6,7,8-HpCDD, a congener indicative of exposure during firefighting, were elevated. Tentative WHO2005-TEQs calculated for PBDD/Fs in our samples (mean 104pgg(-1)lw, range 0.2-734pgg(-1)lw) suggested that PBDD/Fs may contribute substantially to dioxin-like toxicity in individual firefighters. PBDE concentrations were elevated in firefighter serum (mean 135ngg(-1)lw, range 48-442ngg(-1)lw). PBDE-209, PBDE-47 and PBDE-153 were prevalent congeners; PBDE-209 contributed >50% of the total PBDE concentration in four individuals, implying continuous occupational exposure to deca-BDE. Perfluorooctanesulfonate (PFOS) was the dominant PFC in serum (mean 12ngml(-1) (wet weight), ww, range 3ngml(-1)ww to 59ngml(-1)ww), followed by perfluorooctanoic acid (PFOA) (mean 7ngml(-1)ww, range 2ngml(-1)ww to 12ngml(-1)ww). Concentrations of perfluorononanoic acid (PFNA) (mean 2ngml(-1)ww, range 1-4ngml(-1)ww) were higher than those reported in the high-smoke exposure group of World Trade Center fire responders, suggesting that the California firefighters were exposed to PFNA in smoke during firefighting. Given their elevated rates of cancers, these results illustrate the importance of monitoring halogenated contaminants including PBDD/Fs in firefighters.

[Determination of three brominated flame retardants in human serum using solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry].

A solid-phase extraction (SPE) method for the simultaneous extraction of hexabromocyclododecanes (HBCDs)/tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) in human serum was developed. The extracts of HBCDs/TBBPA and PBDEs were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS), respectively. The samples with the spiked internal standards, 13C(12)-HBCD, 13C(12)-TBBPA, 3, 3', 4, 4'-tetrabromodiphenyl ether (BDE-77) and 13C(12)-decabromodiphenyl ether (BDE-209), were extracted using the mixture of methyl tert-butyl ether (MTBE) and hexane (1:1, v/v). Then the co-extracted lipid was removed by sulfuric acid treatment. The newly obtained extract was purified using SPE with an LC-Si column and two fractions of HBCDs/TBBPA and PBDEs were finally got. The determination of HBCDs/TBBPA was performed on a 50 mm BEH C18 column in the multi-reaction monitoring (MRM) mode and the determination of PBDEs was on a 15 m capillary column in the selected ion-monitoring (SIM) mode. The limits of detection (LODs, S/N = 3) ranged from 1.81 to 42.16 pg/g. The average recoveries were from 80.3% to 108.8% at two spiked levels of 0.5 and 5 ng/g for HBCDs, 0.05 and 0.5 ng/g for TBBPA and BDE-209 with the relative standard deviations between 1.02% and 11.42% (n = 5). The developed method has been successfully applied to the determination of the 12 analytes in 42 pooled human serum samples. The levels of TBBPA in the samples ranged from < LOD to 6.58 ng/g, that of alpha-HBCD diastereoisomer ranged from < LOD to 7.22 ng/g, which was the most abundant isomer comparing with beta- and gamma-HBCD. The total PBDEs found ranged from 2.90 to 89.69 ng/g. This method was validated to be accurate and sensitive for the analysis of HBCDs, TBBPA and PBDEs in serum samples.

Plasma concentrations of selected organobromine compounds and polychlorinated biphenyls in postmenopausal women of Québec, Canada.

BACKGROUND: Brominated flame retardants, especially polybrominated diphenyl ethers (PBDEs), have been widely used in North America, but little is known about the level of exposure of human populations to these compounds. OBJECTIVES: We set out to assess the internal exposure of postmenopausal Canadian women to selected organobromine compounds and to investigate factors associated with this exposure. METHODS: We measured concentrations of four PBDEs, one polybrominated biphenyl, and for comparative purposes, 41 polychlorinated biphenyl (PCB) congeners in plasma samples from 110 healthy postmenopausal women who were recruited at a mammography clinic in 2003-2004. RESULTS: PBDE-47 was the major PBDE congener, with a mean (geometric) concentration of 8.1 ng/g lipids and extreme values reaching 1,780 ng/g. By comparison, the mean concentration of the major PCB congener (PCB-153) was 41.7 ng/g and the highest value was 177 ng/g. PBDEs 47, 99, and 100 were strongly intercorrelated, but weaker correlations were noted with PBDE-153. As the sum of PBDEs (summation operatorPBDEs) increased, the relative contribution of PBDE-47 to the summation operatorPBDEs increased, whereas that of PBDE-153 decreased. PBDE-153 was the only brominated compound correlated to PCB-153. PBDE levels were not linked to any sociodemographic, anthropometric, reproductive, or lifestyle variables documented in the present study. Age and body mass index gain since the age of 18 years were significant predictors of PCB-153 plasma levels. CONCLUSION: Our results suggest that exposure to PBDE-47 likely occurs through direct contact with the penta-PBDE formulation, whereas exposure to PBDE-153 may originate in part from the food chain.

Occupational exposure to hexabromocyclododecane at an industrial plant.

Occupational exposure to hexabromocyclododecane (HBCD) among workers at an industrial plant producing expandable polystyrene (PS) added HBCD as flame retardant has been assessed in the present study. Airborne dust samples were collected near the breathing zone of 10 male workers during three 8-h work shifts. The HBCD concentrations in the airborne dust varied from 0.2 to 150 microg/m3 (mean 12.2 and median 2.1 microg/m3). Two serum samples were obtained from each of the workers. The mean serum concentration was 190 ng/g lipids; the median was 101 ng/g lipids (range 6 to 856 ng/g lipids). HBCD was not detected above 1 ng/g lipids (LOD) in any samples from persons in a reference group with no occupational exposure to HBCD. The contribution of gamma-HBCD to the total HBCD serum concentration was notably high (39%) compared to what has usually been observed in biological samples. There was no clear correlation of serum levels with average HBCD concentrations in the airborne dust samples collected near the subjects' breathing zone. The elevated exposure levels reported in this study compared to urban air and serum levels in general populations suggest that further and more detailed exposure assessment studies should be initiated in industries where HBCD is applied.

[Fumigation of soil and food: assessment of occupational exposure to methyl bromide]. / Fumigazione di terreni agricoli e derrate alimentari: la valutazione dell'esposizione professionale a bromuro di metile.

Innovative procedures were developed for the biological monitoring of workers exposed to methyl bromide, through the determination of biomarkers of exposure, such as bromide in serum, and of biomarkers of the biologically effective dose, such as haemoglobin adducts. The effectiveness of the developed techniques for the biological monitoring was tested through the analysis of blood samples from workers employed in soil fumigation.

Glutathione transferase activity and formation of macromolecular adducts in two cases of acute methyl bromide poisoning.

OBJECTIVES: To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute inhalation exposure to methyl bromide. To examine the influence of the polymorphism of glutathione-S-transferase theta (GSTT1) on the neurotoxicity of methyl bromide. METHODS: Two workers acutely exposed to methyl bromide with inadequate respiratory protective devices were poisoned. Seven weeks after the accident, blood samples were drawn from both patients, for measurement of glutathione transferase activity in erythrocytes (conjugator status--that is, GSTT1 phenotype) and measurement of binding products of methyl bromide with blood proteins. Conjugator status was determined by a standard procedure. The binding product of methyl bromide, S-methylcysteine, was measured in globin and albumin. RESULTS: Duration and intensity of exposure were identical for both patients as they worked together with the same protective devices and with similar physical effort. However, one patient had very severe poisoning, whereas the other only developed mild neurotoxic symptoms. The first patient was a "conjugator" with normal glutathone transferase activity, whereas this activity was undetectable in the erythrocytes of the second patient, who consequently had higher concentrations of S-methylcysteine adduct in albumin (149 v 91 nmol/g protein) and in globin (77 v 30 nmol/g protein). CONCLUSIONS: Methyl bromide is genotoxic and neurotoxic. Its genotoxicity seems to be the consequence of the alkylating activity of the parent compound, and conjugation to glutathione has a protective effect. The data presented here suggest a different mechanism for methyl bromide neurotoxicity which could be related to the transformation of methylglutathione into toxic metabolites such as methanethiol and formaldehyde. If such metabolites are the ultimate toxic species, N-acetylcysteine treatment could have a toxifying rather than a detoxifying effect.

Macromolecular adducts in the use of methyl bromide as fumigant.

An HPLC method for analysis of blood protein adducts of methyl bromide was developed. With this method, the alkylated amino acid S-methylcysteine can be quantified both in globin and in serum albumin. The determination of these adducts was implemented in a field study on fumigators who use methyl bromide for the control of insects, nematodes and fungi. Sister chromatid exchange (SCE) was determined in the lymphocytes of the fumigators as an additional biomonitoring parameter. Exposure of persons living in the vicinity of fumigated objects to methyl bromide has been repeatedly reported in the past. The new method for determination of blood protein adducts can be applied for evaluation of such environmental exposure.

Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes.

A hitherto unknown glutathione-S-transferase in human erythrocytes displays polymorphism: three quarters of the population ("conjugators") possess, whereas one quarter ("non-conjugators") lack this specific activity. A standard method for the identification of conjugators and non-conjugators with the use of methyl bromide and gas chromatography (head space technique) is described. Three substrates of the polymorphic enzyme, methyl bromide, ethylene oxide and dichloromethane (methylene chloride), were incubated in vitro with individual whole blood samples of conjugators and non-conjugators. All three substances led to a marked increase of sister chromatid exchanges (SCE) in the lymphocytes of the non-conjugators but not in those of conjugators. A protective effect of the glutathione-S-transferase activity in human erythrocytes for the cytogenetic toxicity of these chemicals in vitro is thus confirmed. Since the enzyme activity is not found in erythrocytes of laboratory animals, species extrapolations for risk assessment of methyl bromide, ethylene oxide and dichloromethane should be reconsidered.