[Effects and significance of continuous hemoperfusion on patients with diquat poisoning].

OBJECTIVE: To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance. METHODS: A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. RESULTS: Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (µg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (µmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ 2 = 7.288, P = 0.007]. CONCLUSIONS: Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

Simultaneous determination of paraquat and diquat in human plasma by HPLC-DAD: Its application in acute poisoning patients induced by these two herbicides.

BACKGROUND: Paraquat and diquat are widely used in agricultural production in many countries, which are very toxic to human beings. Paraquat can be detected in some diquat solution sold in the market. The blood concentration of paraquat or diquat is an important indicator for clinical diagnosis of paraquat or diquat poisoning. So, it is very meaningful to develop a method for simultaneous determination of paraquat and diquat in human plasma. OBJECTIVE: To develop and validate a HPLC-DAD method for simultaneous determination of paraquat and diquat in human plasma and to apply it in the acute poisoning patients by these two herbicides. METHODS: Paraquat and diquat were simultaneously determined by HPLC-DAD. The plasma was treated using Waters OASIS® Column and then separated on a Thermo Hypersil GOLD (250 × 4.6 mm, 5 µm) Column with the mobile phase consisted of 75 mmol/L sodium heptane sulfonate (containing 0.1 mol/L phosphoric acid, pH 3.0) and acetonitrile (87:13, v:v) at a flow rate of 1.0 mL/min. The full-wavelength scanning was 200-400 nm, and the detection wavelength of paraquat and diquat was 257nm and 310nm, respectively. 120 and 30 plasma samples from patients with paraquat and diquat poisoning were collected and analyzed by the established method. RESULTS: The standard curve for paraquat and diquat ranged from 0.05 to 20 µg/mL, and the precision of LLOQ for paraquat was 16.49%, which was required to be less than 20%. The precision of other concentrations was less than 14.14%. The recovery of paraquat and diquat was 95.38%-103.97% and 94.79%-98.40%, respectively. The results showed that paraquat and diquat were stable under various storage conditions. 120 plasma samples of paraquat poisoning patients and 30 plasma samples of diquat poisoning patients were determined by the established method. The blood concentration of paraquat ranged from 0.10 to 20.62 µg/mL, with an average of 3.61 µg/mL, while for diquat, the concentration ranged from 0 to 26.59 µg/mL, with an average of 2.00 µg/mL. Among the diquat suspected poisoning samples, 5 samples were detected not only diquat but also paraquat, and 2 samples were detected only paraquat, no diquat. CONCLUSION: The HPLC-DAD method established in this study was high throughput, high sensitivity, simple operation, and wide linear ranges. It can be used for the screening analysis and quantitative detection of paraquat and diquat in acute poisoning patients, which can provide basis for the treatment and prognosis of these two herbicides poisoning patients.

Forensic evidence of sulfur mustard exposure in real cases of human poisoning by detection of diverse albumin-derived protein adducts.

We present the forensic analyses of plasma samples of human victims exposed to sulfur mustard (SM) in a crisis region in the Middle East in 2015. A few hours after exposure, poisoned persons showed typical signs and symptoms of percutaneous SM exposure including erythema and later on blisters and hardly healing skin wounds. Blood samples were collected 15 days after poisoning to be analyzed for the presence of long-lived protein-adduct biomarkers to verify SM poisoning. We applied a novel bioanalytical toolbox targeting four human serum albumin-derived biomarkers that were made accessible after plasma proteolysis. These adducts contained the SM-specific hydroxyethylthioethyl moiety either bound to the thiol group of a cysteine residue (C34*) or to the side-chain carboxylic group of a glutamic acid residue (E230*). Peptide biomarkers were produced from plasma of the victims using proteinase K (C34*PF), pronase (C34*P) and pepsin (AE230*VSKL and LQQC34*PFEDHVKL) for enzymatic protein cleavage. Separation and detection were carried out by selective micro-liquid chromatography-electrospray ionization high-resolution tandem mass spectrometry (µLC-ESI MS/HR MS). In addition to this site-specific adduct detection, a general approach after alkaline hydrolysis of the plasma protein fraction was applied. Liberated thiodiglycol (TDG) was derivatized with heptafluorobutyric anhydride and detected by gas chromatography-electron ionization mass spectrometry (GC-EI MS). The different bioanalytical methods yielded congruent results confirming SM poisoning for all patients who showed clinical signs and symptoms. This is the first time that real cases of SM poisoning were confirmed and presented by such a broad compilation of protein-derived biomarkers.

Minimum ingested iron cut-off triggering serious iron toxicity in children.

BACKGROUND: Iron intoxication can occur accidentally in children or intentionally by adolescents as a suicide attempt. They usually present with various symptoms including vomiting and diarrhea. Clinical studies in this field has been reported different doses of ingested elemental iron that caused serious toxicity, but none of these studies determined the minimum cut-off of ingested iron that triggered the risk of severe toxicity. The aim of this study was therefore to investigate the demographic features of iron intoxication in Turkish children and to determine the lowest cut-off of ingested elemental iron triggering serious intoxication and the need for prompt management. METHODS: This retrospective study investigated 83 Turkish patients with accidental and intentional iron poisoning. RESULTS: Of the 83 cases of acute iron intoxication, accidental iron consumption was more common than intentional use. Fifty-three patients ingested a median toxic dose of elemental iron of 40.0 mg/kg (IQR, 33.5 mg/kg). The median serum iron concentration in the first 6 h of ingestion was 150 µg/dL (IQR, 282 µg/dL). Twenty patients were given deferoxamine, whereas 63 patients were given supportive treatment. CONCLUSION: The cut-off of ingested elemental iron that triggered serious toxicity and the need for deferoxamine in children <18 years of age was 28 mg/kg.

Paracetamol metabolite concentrations following low risk overdose treated with an abbreviated 12-h versus 20-h acetylcysteine infusion.

CONTEXT: To compare degree of liver injury and paracetamol metabolite concentrations after treatment with standard of care (20-h) vs. abbreviated (12-h) acetylcysteine regimens used in paracetamol overdose (NACSTOP trial). METHODS: Timed blood samples from a cohort of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-h acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) were assayed for paracetamol metabolites as a pilot study, using liquid chromatography/mass spectrometry. Control group subjects received a 20-h course of acetylcysteine (200 mg/kg over 4 h, 100 mg/kg over 16 h). The intervention group received a 12-h acetylcysteine regimen (stopped after at least 12 h of treatment). Positive control groups not in the trial with acute liver injury (ALI) or hepatotoxicity were also studied. RESULTS: One hundred and forty-one blood samples were collected from 40 patients receiving acetylcysteine after paracetamol overdose. Median ALT after 20 h of acetylcysteine was 12 U/L (IQR 8.14) in the abbreviated regimen group, compared to the control group 16 U/L (IQR 11.21) (p = .46). There was no significant difference in median metabolite concentrations on presentation and after 20 h of acetylcysteine between these two groups (p > .05). Presentation median sum CYP-metabolite/total metabolite percentages were 2.5 and 3.0 in the abbreviated and control NACSTOP groups, respectively. CONCLUSIONS: An abbreviated 12-h acetylcysteine regimen for paracetamol overdose used in the NACSTOP trial had similar circulating metabolite concentrations compared to a 20-h regimen in selected subjects with low risk of hepatotoxicity. This suggests that further acetylcysteine may not be needed in the abbreviated group at time of cessation.

Retrospective characterization of canine coagulopathies using the turbidimetric ACL-TOP 300 analyzer (2014-2015): Forty-seven dogs.

OBJECTIVE: To characterize disseminated intravascular coagulation (DIC), liver failure (LF), post-hepatic cholestasis (PHC), and anticoagulant rodenticide intoxication (ROD) in dogs using an immunoturbidimetric coagulation analyzer and to characterize the relationship between clinical bleeding and bleeding parameters. DESIGN: Retrospective study (August 2014-July 2015). SETTING: University teaching hospital. ANIMALS: Forty-seven client-owned dogs diagnosed with DIC (n = 24), LF (n = 9), PHC (n = 5), or ROD (n = 9) based on history, clinical pathology, cytology, histopathology. or exploratory surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median prothrombin time (PT), activated partial thromboplastin time (aPTT), and quantitative fribrinogen assay (QFA) were above the reference interval for DIC, LF, PHC and ROD with the exception of a normal QFA for LF. Clot curve analysis for DIC was characterized by elevated PT Delta, PT first derivative, and aPTT Delta, and normal for aPTT second derivative; all LF parameters were within the RI; all PHC parameters were above the RI; and ROD had elevated aPTT delta, but low aPTT second derivative. Coagulopathic bleeding recognized within the DIC group was characterized by median PT delta in mABS (milliabsorbance), first derivative and aPTT delta values in mABS within the RI at 35.0, 55.5 and 38, respectively. The nonbleeding DIC group median values of these same parameters were 189.5, 586.5 and 288, respectively. CONCLUSIONS: The classically utilized indicators of secondary hemostasis, PT and aPTT, were prolonged within all 4 groups; DIC, LF, PHC and ROD as expected. Fibrinogen concentration was increased in both PHC and ROD, decreased in LF and increased but with a bimodal distribution in DIC that correlated with clinical bleeding. The degree of PT and aPTT prolongation did not correlate with clinical bleeding in the DIC group, however clot curve analysis, did reveal an association.

A simple and economical method of gas chromatography-mass spectrometry to determine the presence of 6 pesticides in human plasma and its clinical application in patients with acute poisoning.

An economical, rapid, and sensitive method of gas chromatography-mass spectrometry (GC-MS) was developed and validated to determine the presence of six pesticides (dichlorvos, acetochlor, atrazine, chlorpyrifos, α-endosulfan, and ß-endosulfan) in human plasma. The pesticides were extracted with acetonitrile and concentrated using anhydrous sodium sulfate. Then, the target compounds were analyzed and quantified with GC-MS using borneol as an internal standard. Separation was performed on a HP-5MS capillary column (30 m × 0.25 mm × 0.25 µm) with temperature programming. Detection was accomplished under electro-spray ionization (ESI) in selected ion monitoring (SIM) mode. Under optimized conditions, satisfactory linear ranges of 0.05-10 µg/mL were obtained for all of the analyzed pesticides. The linear correlation coefficients were greater than 0.99. The average recovery was between 86.8 and 106.5%. The inter- and intra-day precision ranged from 1.7-14.5% and 4.2-13.8%, respectively. Dichlorvos was unstable in plasma both at room temperature and when frozen. The other five pesticides were stable after storage at - 20°C for 17 days and two freeze-thaw cycles. Thirty-five plasma samples from 15 patients with acute self-poisoning were analyzed using this method. Dichlorvos was found in 13 plasma samples with a mean concentration of 0.289 µg/mL, and atrazine was found in 6 with a mean concentration of 0.261 µg/mL. Acetochlor was found in one plasma sample (0.153 µg/mL). This method is simple, reliable and cost-effective. It takes little time and does not waste solvents, and it can be used to routinely detect six pesticides in patients with acute poisoning.

Low-Level Toxic Metal Exposure in Healthy Weaning-Age Infants: Association with Growth, Dietary Intake, and Iron Deficiency.

Even low levels of toxic metal exposure (As, Cd, Hg, and Pb) in infancy might be harmful to children's development. This study investigated toxic metal exposure on healthy weaning-age infants and its relationship with growth, diet, and iron/anemia status. The weight, height, head circumference, whole blood levels of four toxic metals, hemoglobin, and serum ferritin of healthy infants was measured. Among 210 infants with a median age of 11.4 months (interquartile range: 10.5-12.0), the median levels of As, Cd, Hg, and Pb were 1.2 µg/L, 0.05 µg/L, 0.8 µg/L, and 0.83 µg/dL, respectively. In adjusted linear regression models, post-birth weight gain (Pb) and current head circumference (As, Pb) were negatively associated with toxic metal levels. In multiple linear regression or logistic regression analysis, the duration of breastfeeding (all four metals), perceived adequacy of rice-based food intake (As), regular fish intake (As, Hg), and iron deficiency with/without anemia (Cd, Pb) were associated with increased toxic metal levels. Although levels of toxic metals may not usually be high in this population, individual exposure risk may need to be assessed after considering the type of feeding or intake of complementary foods and the iron/anemia status while evaluating growth status during late infancy.

Metallosis Identified via Intraoperative Cell Salvage: A Case Report.

Intraoperative cell salvage, whereby shed surgical blood is recovered for autologous reinfusion, is frequently used during hip arthroplasty because of the potential for significant blood loss. The following cases describe 2 instances in which chromium and cobalt particles from patients' metal-on-metal hip implants were identified within the blood recovery system. Results of heavy metal testing during the second case suggest that the use of a leukocyte reduction filter effectively reduces metal concentrations to below normal circulating levels. However, the reinfusion of cell salvage blood containing obvious metallic particles cannot be recommended until the effectiveness of leukocyte reduction filters in removing heavy metals has been further tested.

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning.

CONTEXT: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. OBJECTIVE: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. METHODS: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. RESULTS: The acute maximum (Cmax) LT concentrations were higher than concentrations in survivors: Cmax for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. CONCLUSIONS: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.

Serum Calcium Concentration in Ethylene Glycol Poisoning.

INTRODUCTION: The diagnosis of ethylene glycol intoxication can be challenging. Definitive testing for ethylene glycol is not readily available and clinical decisions are often based on clinical suspicion and the results of more readily available tests. One of these findings is hypocalcemia, presumable through complexation with the ethylene glycol metabolite oxalate. METHODS: We performed a retrospective review of all patients admitted to a tertiary care hospital between 2005 and 2013 with laboratory confirmed ethylene glycol intoxication. Serum calcium on presentation was compared to blood gas pH on presentation as well as presentation serum bicarbonate. RESULTS: We did not find any relationship between calcium and serum pH either by linear regression or when dichotomized by pH ≥ or <7.3. We did observe an inverse relationship between serum calcium and bicarbonate. CONCLUSIONS: Hypocalcemia is not commonly observed following ethylene glycol poisoning, even in acidotic patients.

Alterações leucocitárias ocasionadas pelo estresse toxicológico agudo do óleo diesel em juvenis de tilápia-do-nilo / Change in leukocyte by acute toxicological stress of diesel oil in juveniles of Nile tilapia

O presente trabalho teve como objetivo avaliar o estresse e as alterações no leucograma dos juvenis de Oreochromis niloticus submetidos à toxicidade aguda do óleo diesel. A toxicidade foi avaliada em um delineamento inteiramente casualizado com cinco diluições (20, 25, 30, 35 e 40%) e um controle, ambos com três repetições. Para a avaliação dos níveis glicêmicos e alteração no leucograma, foi retirado sangue por punção caudal dos peixes moribundos. Dessa forma, conclui-se que o óleo diesel pode apresentar riscos ao ecossistema aquático, provocando toxicidade aos organismos aquáticos e alterações fisiológicas.(AU)

This study aimed to evaluate the stress and changes in white blood cell count of juveniles Oreochromis niloticus subjected to acute toxicity of diesel oil. The toxicity was evaluated in a completely randomized design with five dilutions (20, 25, 30, 35 and 40%) and one control, both with three replicates. For the assessment of blood glucose levels and changes in white blood cell count, blood was drawn by caudal puncture of the dying fish. It was concluded that diesel oil can present risks to aquatic ecosystem, causing toxicity and physiological changes to fish.(AU)

Recent progress toward the use of circulating microRNAs as clinical biomarkers.

MicroRNAs (miRNAs) have been shown to be critical mediators of many cellular and developmental processes and have been implicated in different human diseases. Since the observation of extracellular miRNAs present in various biofluids, much attention and excitement have been garnered toward understanding the functional roles of these circulating extracellular miRNAs and establishing their potential use as noninvasive diagnostic biomarkers. Here, we will review the current state of miRNA biomarkers for many human diseases, including their emerging use in toxicological applications, and discuss the current challenges in the field, with an emphasis on technical issues that often hinder discovery-based miRNA biomarker studies.

SERUM ANTIOXIDANT PARAMETERS IN PATIENTS POISONED BY DIFFERENT XENOBIOTICS.

There is a great diversity of the acute drugs overdose cases in clinical toxicology. Clinical situation is complicated by the coexistence of factors predisposing to the development of adverse drug reactions (chronic use of drugs, polypharmacy, alcohol or drugs dependence, nutritional disorders) and by the presence of chronic organ damage, especially the liver and the kidney. The aim of this study was to evaluate whether there are sensitive plasma markers belonging to the antioxidant system in patients exposed to various xenobiotics. We measured the activity of antioxidant parameters: catalase (CAT), glutathione peroxidase (GPX3), glutathione (GSH), sulfhydryl groups (-SH), carbonyl groups (=CO) and free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH, assay) in serum of 49 patients with acute intoxication caused by carbamazepine (CBZ, n = 9), mixed drug intoxication (MDI) (n = 9), alcohol withdrawal syndrome (AWS, n = 9), acetaminophen (APAP, n = 7), tricyclic antidepressants (TCAs) (n = 5), valproic acids (VA, n = 4), narcotics (N, n = 3), and three others (benzodiazepines, BZD, n = 2; barbiturates, n = 1). The results were compared with the parameters of not intoxicated patients (n = 39). All patients had lower catalase activity in comparison to the control group (41.9 ± 16.5 vs. 196.0 ± 82.2 U/mg protein, p = 0.000), while the increase of GSH level was particularly apparent only in patients with AWS (391.3 ± 257.9 µmol/mg protein) compared to the control group (171.4 ± 88.4 µmol/mg protein, p = 0.034) and to patients intoxicated with carbamazepine (152.8 ± 102.5 µmol/mg protein, p = 0.027). Some differences, but without statistical significance, were also observed in GPX3 activity between different groups of poisoned patients.

Potassium Dichromate Toxicities: Protective Effect of Methanol Extract of Corchorus olitorius in Albino Rats.

Exposure to hexavalent chromate compounds such as other human carcinogens is unavoidable in the developing countries of the world. Research efforts are being directed toward minimizing exposure to them, intercepting their activity in vivo, and/or prophylaxis. The present study therefore evaluates the effect of methanol extract of the leafy vegetable, Corchorus olitorius (MECO), against potassium dichromate (K2Cr2O7)-induced toxicities. Negative control animals were fed distilled water, while the positive control rats received 12 mg/kg body weight K2Cr2O7 once a week for 6 weeks. Test rats were exposed daily to 25, 50, and 100 mg/kg body weight MECO alone for 6 weeks and 12 mg/kg body weight of K2Cr2O7 once a week for 6 weeks before sacrifice. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was monitored in bone marrow cells, while induction of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels, and hematological parameters were assessed in the plasma. The phytochemical analysis of MECO was also carried out. K2Cr2O7 significantly (P < .05) increased the levels of mPCEs, AST, ALT, creatinine, total white blood cells, and lymphocytes compared with the control. The percentage pack cell volume and neutrophils were, however, reduced. In contrast, MECO at different doses restored the markers toward the levels of the negative control. MECO is rich in flavonoids, saponins, anthraquinones, terpenoids, and phenols, and they might be responsible for the protective effect observed in this study. Our results suggest that MECO has a promising potential in the treatment/management of chromate-induced toxicities.

Use of a Rapid Ethylene Glycol Assay: a 4-Year Retrospective Study at an Academic Medical Center.

Ethylene glycol (EG) is a common cause of toxic ingestions. Gas chromatography (GC)-based laboratory assays are the gold standard for diagnosing EG intoxication. However, GC requires specialized instrumentation and technical expertise that limits feasibility for many clinical laboratories. The objective of this retrospective study was to determine the utility of incorporating a rapid EG assay for management of cases with suspected EG poisoning. The University of Iowa Hospitals and Clinics core clinical laboratory adapted a veterinary EG assay (Catachem, Inc.) for the Roche Diagnostics cobas 8000 c502 analyzer and incorporated this assay in an osmolal gap-based algorithm for potential toxic alcohol/glycol ingestions. The main limitation is that high concentrations of propylene glycol (PG), while readily identifiable by reaction rate kinetics, can interfere with EG measurement. The clinical laboratory had the ability to perform GC for EG and PG, if needed. A total of 222 rapid EG and 24 EG/PG GC analyses were documented in 106 patient encounters. Of ten confirmed EG ingestions, eight cases were managed entirely with the rapid EG assay. PG interference was evident in 25 samples, leading to 8 GC analyses to rule out the presence of EG. Chart review of cases with negative rapid EG assay results showed no evidence of false negatives. The results of this study highlight the use of incorporating a rapid EG assay for the diagnosis and management of suspected EG toxicity by decreasing the reliance on GC. Future improvements would involve rapid EG assays that completely avoid interference by PG.

[Acute poisoning with e-cigarette liquid ­ case report].

Spreading e-cigarettes popularity comes from relief, the products are safe. They don't contain carcinogenic substances, that are present in tobacco smoke. But nicotine present in e-liquid is a very toxic alkaloid, highly addictive. A case of acute, oral intoxication with e-liquid was described. A patient, 42-years old woman, e-cigarettes addicted, health thus far, by accident drunk a swig of e-liquid containing nicotine at concentration 6 mg/ml. At admission to Toxicology Department she was conscious, with symptoms: dizziness, flushed cheeks, dry skin, dry conjunctivas, medium-wide pupils, nervous twitch, tachycardia, elevated blood pressure. Concentration of cotinine ­ nicotine metabolite, in serum and urine were respectively 2077 and 10236 ng/ml. Applied treatment was: infusive liquids, intravenous alkalization, administration of electrolytes and propranolol. Gradually improvement was reached and on the third day of hospitalization, after psychiatric consultation she was deinstitutionalized in good medical condition to continue treatment in Neurology Clinic. E-fluid intoxications are rare, poisoning course depends on nicotine dose, way of absorption, patient's health state and age.

Orchiectomy attenuates oxidative stress induced by aluminum in rats.

The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.

Optimized verification method for detection of an albumin-sulfur mustard adduct at Cys(34) using a hybrid quadrupole time-of-flight tandem mass spectrometer after direct plasma proteolysis.

The vesicant sulfur mustard (SM) is a banned chemical warfare agent that is controlled by the Organisation for the Prohibition of Chemical Weapons (OPCW). Bioanalytical procedures are mandatory for proving an alleged use and incorporation of SM into the body. We herein present the development and application of a novel optimized procedure suitable for qualitative verification analysis of plasma targeting the SM-adduct of human serum albumin (HSA) alkylated at the cysteine(34) residue. Diluted human plasma is directly mixed with pronase in an ultrafiltration device (10kDa cut-off) for proteolysis (4h, 37°C). Following ultrafiltration the filtrate is diluted and analyzed by microbore liquid chromatography-electrospray ionization high resolution tandem-mass spectrometry (µLC-ESI HR MS/MS) targeting the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP). A hybrid quadrupole time-of-flight mass spectrometer provided high mass spectrometric resolution in the MS/MS mode enabling highest selectivity and sensitivity (lower limit of detection corresponding to 9.8nM SM in plasma). Kinetics of HETE-CP formation from heparin-, citrate-, and EDTA-plasma as well as serum are presented and the influence of different EDTA and pronase concentrations was characterized. The novel procedure was applied to plasma samples provided by the OPCW as well as to patients plasma derived from real cases of SM-poisoning.

Metal concentrations in the blood and tissues after implantation of titanium growth guidance sliding instrumentation.

BACKGROUND: Growth guidance sliding treatment devices, such as Shilla (Medtronic, Minneapolis, MN USA) or LSZ-4D (CONMET, Moscow, Russia), used for the treatment of scoliosis in children who have high growth potential have unlocked fixtures that allow rods to slide during growth of the spine, which avoids periodical extensions. However, the probability of clinical complications associated with metallosis after implantation of such devices is poorly understood. The content of metal ions in the blood and tissues of pediatric patients treated for scoliosis using fusionless growth guidance sliding instrumentation has not yet been investigated. PURPOSE: The aim of the present study was to measure the content of metal ions in the blood and tissues surrounding the implanted growth guidance sliding LSZ-4D devices made of titanium alloy (Ti6Al4V), and to identify the incidence of metallosis-associated clinical complications in some patients with these devices. STUDY DESIGN: This is a one-center, case-control retrospective study. PATIENTS SAMPLE: The study group included 25 patients with high growth potential (22 females, 3 males; average age at primary surgery for scoliosis treatment is 11.4±1.2 years old) who had sliding growth guidance instrumentation LSZ-4D (CONMET) implanted on 13 (range: 10-16) spine levels for 6±2 years. The LSZ-4D device was made from titanium alloy Ti6Al4V and consisted of two rectangular section rods and fixture elements. Locked fixtures were used on one spinal level, whereas the others were unlocked (sliding). The control group consisted of 13 patients (12 females and 1 male; 11±1.2 years old) without any implanted devices. OUTCOME MEASURES: The content of Ti, Al, and V metal ions in the whole blood and tissues around the implanted device was measured. The incidences of metallosis-associated complications in the study group were recorded. METHODS: Metal ion content was measured by the inductively coupled mass spectrometry method on quadrupolar NexION 300D (PerkinElmer Inc, Shelton, CT, USA). RESULTS: Five of 25 patients in the study group developed metallosis-associated complications (two sinuses and three seroma in the lumbar part of the spine). Revisions were carried out in two of these patients. Ninety percent of the patients in the study group had increased content of Ti and V ions in the blood (2.8 and 4 times, respectively). Median content of Ti ions in soft tissues adjacentto implanted sliding device was more than 1,500-fold higher than that of the control group. These levels are much higher than previously reported for spinal instrumentation. CONCLUSIONS: Increased content of Ti and V ions in the blood and especially in tissues around the titanium growth guidance sliding device LSZ-4D accompanied by clinical manifestations (seroma and sinuses) indicates the importance of improving wear resistance of such instrumentation with the coatings and the necessity to exchange sliding instrumentation once the child is fully grown.