Methanol mass poisoning is a global problem with high fatality rates and often severe sequelae in survivors. Patients typically present late to the hospital with severe metabolic acidosis followed by a rapid deterioration in their clinical status. The hypothesis 'Circulus hypoxicus' describes the metabolic acidosis following methanol poisoning as a self-enhancing hypoxic circle responsible for methanol toxicity. We wanted to test the validity of this hypothesis by an observational study based on 35 patients from the methanol outbreaks in Norway (2004) and the Czech Republic (2012). Comprehensive laboratory values, including S(serum)-methanol, S-formate, S-lactate, arterial blood gases, anion and osmolal gaps, were used in the calculations. Laboratory values and calculated gaps were compared to each other using linear regression. S-lactate and S-formate correlated better with the increased base deficit and anion gap than did S-formate alone. Base deficit rose to about 20 mmol/L and S-formate rose to 12 mmol/L prior to a significant rise in S-lactate - most likely caused by formate inhibition of mitochondrial respiration (type B lactacidosis). The further rise in S-lactate was not linear to S-formate most likely due to the self-enhancing pathophysiology, but may also be associated with hypotension in critically ill patients and variable ethanol drinking habits. Our study suggests that the primary metabolic acidosis leads to a secondary lactic acidosis mainly due to the toxic effects of formate. The following decline in pH will further increase this toxicity. As such, a vicious and self-enhancing acidotic circle may explain the pathophysiology in methanol poisoning, namely the 'Circulus hypoxicus'.

• MeSH
• acidobazická rovnováha účinky léků   MeSH
• acidóza chemicky indukované   MeSH
• analýza krevních plynů MeSH
• dospělí MeSH
• formiáty krev   MeSH
• kyselina mléčná krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol krev   otrava   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• poruchy acidobazické rovnováhy chemicky indukované   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• formiáty MeSH
• formic acid MeSH Prohlížeč
• kyselina mléčná MeSH
• methanol MeSH

In this work, a simple device for extremely fast separation of blood plasma from diluted whole blood was developed. The device accommodates an asymmetric polysulfone membrane/supporting membrane sandwich that allows collection of 10 µL blood plasma into a narrow glass capillary in less than 10 s. The composition of diluent solution was optimized in order to achieve maximum recoveries for selected metabolites of alcohol intoxication. 5% solution of [tris(hydroxymethyl)methylamino] propanesulfonic acid provided recoveries of formate, oxalate and glycolate close to 100% and only moderate erythrocyte lysis. Both charged and uncharged compounds from the whole blood samples can be analyzed in the separated blood plasma by capillary electrophoresis with contactless conductometric detection and spectrophotometry, respectively. The developed device might find wide application in on-site testing and point-of-care analysis, when only microliter volumes of whole blood are available.

• Klíčová slova
• Alcohol intoxication, Blood plasma separation, Capillary electrophoresis, Metabolites, Methanol, Point of care analysis,
• MeSH
• elektroforéza kapilární přístrojové vybavení   MeSH
• formiáty krev   MeSH
• glykoláty krev   MeSH
• lidé MeSH
• oxaláty krev   MeSH
• spektrofotometrie přístrojové vybavení   MeSH
• vyšetření u lůžka * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• formiáty MeSH
• formic acid MeSH Prohlížeč
• glycolic acid MeSH Prohlížeč
• glykoláty MeSH
• oxaláty MeSH

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.

• Klíčová slova
• Neuroinflammation, brain damage, leukotrienes, methanol poisoning, nontraumatic brain injury, sequelae of poisoning,
• MeSH
• akutní nemoc MeSH
• cystein krev   MeSH
• ethanol krev   MeSH
• formiáty krev   MeSH
• hospitalizace MeSH
• hydrogenuhličitany krev   MeSH
• koncentrace vodíkových iontů MeSH
• kreatinin krev   MeSH
• krevní glukóza metabolismus   MeSH
• laktáty krev   MeSH
• leukotrieny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol krev   otrava   MeSH
• mozek účinky léků   patologie   MeSH
• následné studie MeSH
• neurodegenerativní nemoci chemicky indukované   patologie   MeSH
• otrava krev   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět chemicky indukované   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cystein MeSH
• cysteinyl-leukotriene MeSH Prohlížeč
• ethanol MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• hydrogenuhličitany MeSH
• kreatinin MeSH
• krevní glukóza MeSH
• laktáty MeSH
• leukotrieny MeSH
• methanol MeSH

The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non-haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• dospělí MeSH
• formiáty krev   MeSH
• heparin terapeutické užití   MeSH
• hospitalizace MeSH
• koncentrace vodíkových iontů MeSH
• krvácení chemicky indukované   farmakoterapie   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• methanol krev   otrava   MeSH
• mozek účinky léků   patologie   MeSH
• následné studie MeSH
• nemoci mozku chemicky indukované   farmakoterapie   epidemiologie   MeSH
• otrava farmakoterapie   epidemiologie   MeSH
• prevalence MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• heparin MeSH
• methanol MeSH

OBJECTIVES: We report the results of the visual evoked potentials (VEP) examination in patients after severe poisoning by methanol. MATERIAL AND METHODS: The group of 47 patients (38 males and 9 females) was assembled out of persons who survived an outbreak of poisoning by the methanol adulterated alcohol beverages, which happened in the Czech Republic in 2012-2013. The visual evoked potentials examination was performed using monocular checkerboard pattern-reversal stimulation. Two criteria of abnormality were chosen: missing evoked response, and wave P1 latency > 117 ms. Non-parametric statistical methods (median, range, and the median test) were used to analyze factors influencing the VEP abnormality. RESULTS: The visual evoked potential was abnormal in 20 patients (43%), 5 of them had normal visual acuity on the Snellen chart. The VEP abnormality did not correlate significantly with initial serum concentrations of methanol, formic acid or lactate; however, it showed statistically significant inverse relation to the initial serum pH: the subgroup with the abnormal VEP had significantly lower median pH in comparison with the subgroup with the normal VEP (7.16 vs. 7.34, p = 0.04). The abnormality was not related to chronic alcohol abuse. CONCLUSIONS: The visual evoked potentials examination appeared sensitive enough to detected even subclinical impairment of the optic system. Metabolic acidosis is likely to be the key factor related to the development of visual damage induced by methanol. The examination performed with a delay of 1-9 months after the poisoning documented the situation relatively early after the event. It is considered as a baseline for the planned long-term follow-up of the patients, which will make it possible to assess the dynamics of the observed changes, their reversibility, and the occurrence of potential late sequelae.

• Klíčová slova
• Czech Republic, VEP, acidosis, methanol, poisoning, visual evoked potentials,
• MeSH
• dospělí MeSH
• formiáty krev   MeSH
• koncentrace vodíkových iontů MeSH
• kyselina mléčná krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol krev   farmakologie   otrava   MeSH
• mladý dospělý MeSH
• senioři MeSH
• zraková ostrost MeSH
• zrakové evokované potenciály účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• formiáty MeSH
• formic acid MeSH Prohlížeč
• kyselina mléčná MeSH
• methanol MeSH

A novel, easy to use and portable capillary electrophoretic instrument for injection of small volumes of biological fluids equipped with contactless conductivity detection was constructed. The instrument is lightweight (<5 kg), all necessary parts including a tablet computer are accommodated in a plastic briefcase with dimensions 20 cm × 33 cm × 17 cm (w × l × h), allows hydrodynamic injection of small sample volumes and can continuously operate for at least 10 hours. The semi-automated hydrodynamic sample injection is accomplished via a specially designed PMMA interface that is able to repeatedly inject sample aliquots from a sample volume as low as 10 μL, with repeatability of peak areas below 5%. The developed interface and the instrument were optimized for the injection of biological fluids. Practical utility was demonstrated on the determination of formate in blood serum samples from acute methanol intoxication patients and on the analysis of ionic profile (nitrosative stress markers, including nitrite and nitrate) in the exhaled breath condensate from one single exhalation.

• Klíčová slova
• Contactless conductivity detection, Exhaled breath condensate, Low sample volume, Methanol intoxication, Portable capillary electrophoresis,
• MeSH
• dechové testy MeSH
• dusičnany analýza   MeSH
• dusitany analýza   MeSH
• elektroforéza kapilární přístrojové vybavení   metody   MeSH
• feces chemie   MeSH
• formiáty krev   MeSH
• lidé MeSH
• methanol otrava   MeSH
• tělesné tekutiny chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dusičnany MeSH
• dusitany MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• methanol MeSH

A simple, cost effective, and fast gas chromatography method with mass spectrometry detection (GC-MS) for simultaneous measurement of formic acid, glycolic acid, methoxyacetic acid, ethoxyacetic acid and 2-hydroxyethoxyacetic acid in serum and urine was developed and validated. This multi-analyte method is highly suitable for clinical and emergency toxicology laboratory diagnostic, allowing identification and quantification of five most common acidosis inducing organic acids present in cases of alcohol intoxication. Furthermore, when patients are admitted to emergency unit at late stage of toxic alcohol intoxication, the concentration of parent compound may be already low or not detectable. This new method employs a relatively less used class of derivatization agents - alkyl chloroformates, allowing the efficient and rapid derivatization of carboxylic acids within seconds. The entire sample preparation procedure is completed within 5 min. The optimal conditions of derivatization procedure have been found using chemometric approach (design of experiment). The calibration dependence of the method was proved to be quadratic in the range of 25-3000 mg L(-1), with adequate accuracy (97.3-108.0%) and precision (<12.8%). The method was successfully applied for identification and quantification of the selected compounds in serum of patients from emergency units.

• Klíčová slova
• Alcohol intoxication, Chloroformate, GC–MS, Metabolic acidosis, Organic acid,
• MeSH
• acetáty krev   moč   MeSH
• acidóza diagnóza   MeSH
• analýza moči metody   MeSH
• biochemická analýza krve metody   MeSH
• chemické techniky analytické MeSH
• formiáty krev   moč   MeSH
• glykoláty krev   moč   MeSH
• kalibrace MeSH
• lidé MeSH
• limita detekce MeSH
• otrava alkoholem krev   moč   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí metody   MeSH
• reprodukovatelnost výsledků MeSH
• toxikologie metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetáty MeSH
• beta-hydroxyethoxyacetic acid MeSH Prohlížeč
• ethoxyacetic acid MeSH Prohlížeč
• formiáty MeSH
• formic acid MeSH Prohlížeč
• glycolic acid MeSH Prohlížeč
• glykoláty MeSH
• methoxyacetic acid MeSH Prohlížeč

OBJECTIVE: To present a case of survival without visual and central nervous system sequelae at a formate concentration of twice the reported lethal level. CLINICAL PRESENTATION AND INTERVENTION: This was a case of a 33-year-old man who ingested 1 liter of a toxic mixture of methanol and ethanol. Upon admission, he presented with anxiety, tachycardia and hypertension and had a serum formate level of 1,400 mg/l (normal range 0.9-2.1 mg/l), a methanol level of 806 mg/l (normal range 2-30 mg/l), an undetectable ethanol concentration and a normal lactate level. A 10% solution of ethanol and folinic acid was administered intravenously and two 8-hour sessions of intermittent hemodialysis were performed. The patient was discharged on the fifth day without sequelae of poisoning. The follow-up examinations 3 months and 2 years later revealed no damage to the basal ganglia. The patient had normal visual-evoked potential and findings on optical coherence tomography. The genetic analysis revealed a rare minor allele for the gene coding CYP2E1 enzyme of the microsomal ethanol oxidizing system. CONCLUSION: The patient survived acute methanol poisoning without long-term sequelae despite a high serum level of formic acid upon admission.

• MeSH
• dialýza ledvin MeSH
• dospělí MeSH
• ethanol otrava   MeSH
• formiáty krev   MeSH
• leukovorin aplikace a dávkování   MeSH
• lidé MeSH
• methanol otrava   MeSH
• otrava terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ethanol MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• leukovorin MeSH
• methanol MeSH

Polymer inclusion membranes (PIMs) have several important features, i.e., PIMs are dry and non-porous membranes, which can be prepared ahead of use and stored without noticeable deterioration in extraction performance. In this contribution, in-line coupling of microextractions across PIMs to a separation method for clinical purposes was demonstrated for the first time. Formate (the major metabolite in methanol poisoning) was determined in undiluted human serum and whole blood by capillary zone electrophoresis (CZE) with simultaneous capacitively coupled contactless conductivity detection (C(4)D) and UV-Vis detection. A purpose-made microextraction device with PIM was coupled to a commercial CZE instrument in order to ensure complete automation of the entire analytical procedure, i.e., of formate extraction, injection, CZE separation and quantification. PIMs for formate extractions consisted of 60% (w/w) cellulose triacetate as base polymer and 40% (w/w) Aliquat™ 336 as anion carrier. The method was characterized by good repeatability of peak areas (≤7.0%) and migration times (≤0.8%) and by good linearity of calibration curves (r(2) = 0.993-0.999). Limits of detection in various matrices ranged from 15 to 54 μM for C(4)D and from 200 to 635 μM for UV-Vis detection and were sufficiently low to clearly distinguish between endogenous and toxic levels of formate in healthy and methanol intoxicated individuals. In addition, PIMs proved that they may act as phase interfaces with excellent long-term stability since once prepared, they retained their extractions properties for, at least, two months of storage.

• Klíčová slova
• Blood samples, Capillary electrophoresis, Methanol intoxication, Microextraction, Polymer inclusion membranes,
• MeSH
• celulosa analogy a deriváty   chemie   MeSH
• design vybavení MeSH
• elektroforéza kapilární ekonomika   přístrojové vybavení   metody   MeSH
• formiáty krev   izolace a purifikace   MeSH
• lidé MeSH
• limita detekce MeSH
• membrány umělé * MeSH
• methanol otrava   MeSH
• mikroextrakce na pevné fázi ekonomika   přístrojové vybavení   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cellulose triacetate MeSH Prohlížeč
• celulosa MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• membrány umělé * MeSH
• methanol MeSH

A simple, cost-effective headspace gas chromatography (GC) method coupled with GC with flame ionization detection for simultaneous determination of methanol, ethanol and formic acid was developed and validated for clinical and toxicological purposes. Formic acid was derivatized with an excess of isopropanol under acidic conditions to its volatile isopropyl ester while methanol and ethanol remained unchanged. The entire sample preparation procedure is complete within 6 min. The design of the experiment (the face-centered central composite design) was used for finding the optimal conditions for derivatization, headspace sampling and chromatographic separation. The calibration dependences of the method were quadratic in the range from 50 to 5,000 mg/L, with adequate accuracy (89.0-114.4%) and precision (<12%) in the serum. The new method was successfully used for determination of selected analytes in serum samples of intoxicated patients from among those affected by massive methanol poisonings in the Czech Republic in 2012.

• MeSH
• chromatografie plynová MeSH
• ethanol krev   moč   MeSH
• formiáty krev   moč   MeSH
• kalibrace MeSH
• lidé MeSH
• methanol krev   moč   MeSH
• plamínková ionizace MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ethanol MeSH
• formiáty MeSH
• formic acid MeSH Prohlížeč
• methanol MeSH