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Absztrakt: Az őszi és téli meghűléses időszakban sokan vásárolnak különböző, vény nélkül kapható, megfázás elleni készítményeket, ezen belül is nagy számban paracetamol- (más néven acetaminofén-) tartalmú szereket. A paracetamol különböző típusú fájdalmak (fejfájás, migrén, meghűlés-láz okozta fájdalom, fogfájás, menstruációs fájdalom stb.) enyhítésére szolgáló, igen népszerű, a nemopioid típusú analgetikumok közé sorolható hatóanyag, amely többek között tabletta, kúp és oldat formájában is elérhető a gyógyszertárakban. Magyarországon 2020-ban 86, törzskönyvezett paracetamoltartalmú készítmény van forgalomban. A paracetamol alkalmazása biztonságos és hatékony, amennyiben az előírásnak megfelelően használják. Közleményünkben három olyan esetet mutatunk be, amelyben a beteg halála összefüggésbe hozható a paracetamol alkalmazásával. Mindhárom, krónikus alkoholizmusban szenvedő beteg (34, 42 és 51 évesek) rövid idővel a kórházba kerülés után elhunyt. Vizsgálataink során három betegből származó, összesen kilenc szérumminta került feldolgozásra. A paracetamolnak és metabolitjainak együttes meghatározása enzimatikus módszerrel (Roche assay) történt, míg a paracetamol specifikus mérésére tandem-tömegspektrométerrel kapcsolt szuperkritikus folyadékkromatográfot (SFC–MS/MS) alkalmaztunk. Enzimatikus meghatározással mindegyik mintában terápiás koncentrációt mutattunk ki. SFC–MS/MS módszerrel történt meghatározás esetén egy betegtől származó négy mintában a terápiás tartománynál alacsonyabb paracetamolkoncentrációkat mértünk. A paracetamolterápia alkalmazása krónikus alkoholizmusban szenvedő betegek esetén fokozott kockázatot jelent. A klinikai toxikológiai gyakorlatban a paracetamol meghatározására használt enzimatikus módszer eredményét a máj- és vesefunkciós paraméterekkel együttesen szükséges értékelni, mert krónikus alkoholizmusban szenvedő betegek esetén az enzimatikus módszerrel kapott terápiás tartományba eső koncentráció nem zárja ki a paracetamoltoxicitást. Orv Hetil. 2020; 161(40): 1720–1723.

Background: Simultaneous determination of the two main actin scavenger proteins in sepsis has not been investigated until now. In our pilot study, we elucidated the predictive values of Gc globulin and gelsolin (GSN) in sepsis by comparing them to classic laboratory and clinical parameters. Methods: A 5-day follow-up was performed, including 46 septic patients, 28 non-septic patients and 35 outpatients as controls. Serum Gc globulin and GSN levels were determined by automated immune turbidimetric assay on a Cobas 8000/c502 analyzer. Patients were retrospectively categorized according to the sepsis-3 definitions, and 14-day mortality was also investigated. Results: First-day GSN also differentiated sepsis from non-sepsis (AUC: 0.88) similarly to C-reactive protein (AUC: 0.80) but was slightly inferior to procalcitonin (PCT) (AUC: 0.98) with a cutoff value of GSN at 22.29 mg/L (sensitivity: 83.3%; specificity: 86.2%). Only first-day SOFA scores (0.88) and GSN (0.71) distinguished septic survivors from non-survivors, whereas lactate (0.99), Gc globulin (0.76) and mean arterial pressure (MAP) (0.74) discriminated septic shock from sepsis. Logistic regression analyses revealed SOFA scores and GSN being significant factors regarding 14-day mortality. First-day GSN levels were higher (p Conclusions: Both serum GSN and Gc globulin may have predictive values in sepsis. Considering the small sample size of our study, further measurements are needed to evaluate our results. Measurement of Gc globulin and GSN maybe useful in assessment of sepsis severity and in therapeutic decision-making.

Introduction Besides routine serum markers of inflammatory diseases, the diagnostic potential of selected urinary proteins has not been fully exploited yet. Former studies revealed that urinary orosomucoid (u-ORM) might have complementary information in inflammatory disorders. Our aim was to develop and validate a fully automated method for u-ORM measurements and to evaluate its potential clinical impact on systemic inflammatory diseases. Materials and methods A particle-enhanced immune turbidimetric assay was validated for a Cobas 8000/c502 analyzer to determine u-ORM levels. Spot urine samples from 72 healthy individuals, 28 patients with Crohn's disease and 30 septic patients were studied. Results Our assay time was 10 minutes and the detection limit of u-ORM was 0.02 mg/L. The intra- and inter-assay imprecision expressed as CV was less than 5%, and the recovery ranged between 95-103%. Within 10 to 60 years of age, a preliminary reference range for urinary orosomucoid/creatinine ratio (u-ORM/u-CREAT) was found to be 0.08 (0.01-0.24) mg/mmol [median (2.5-97.5 percentiles)]. Compared to controls, a five-fold increase of u-ORM/u-CREAT values in Crohn's disease and approximately a 240-fold increase in sepsis were observed. Conclusions We set up a fast, sensitive and precise turbidimetric approach for automated u-ORM determination. Our highly sensitive assay is ideal for routine u-ORM measurements and might be a potential novel laboratory test in the management of systemic inflammatory processes.

New psychoactive stimulants appeared in Hungary in 2010 as in several other European countries. We present our findings from cases where new psychoactive and conventional stimulants (we listed amphetamine, methamphetamine and MDMA as conventional drugs) have been detected in biological specimens between 2010 and 2019. Materials Biological samples (including urine, blood and body tissues), sent to the Department of Forensic Medicine, University of Pecs, South-West Hungary, in the period 2010–2019. Method High performance liquid chromatography coupled with diode array detection (HPLC-DAD); supercritical fluid chromatography coupled to tandem mass spectrometry (SFC-MS/MS). Results During the nine-year period between 2010 and 2019, we found new stimulants in 973 (21.1%) cases, and conventional stimulants in 658 (14.2%) cases (out of 4604 analyses −100%- of samples sent to the laboratory for toxicology screening). 594 (12.9%) of all cases were post mortem analyses. The new drugs we’ve detected could be classified into three groups based on their chemical structure: cathinones (in 960 from our cases), substituted phenethylamines (8), and tryptamines (5). The most frequently identified new psychoactive stimulants were (in the order of decreasing frequency): pentedrone (2 6 2), mephedrone (1 8 8), N-ethylhexedrone (1 2 6), methylenedioxypyrovalerone (MDPV; 98), α-pyrrolidinopentiophenone (alpha-PVP; 93), 4-CMC (35). Conclusion The new substances were detected in highest proportion in 2011; by 2018, the number of conventional drugs exceeded the new stimulants in our cases. According to the data of the Hungarian seizures, the decrease was predictable: from 2015, the seizures of traditional stimulants exceeded the seizures of new stimulants. In 2019 the new stimulants were dominated again among the detected substances in the samples.

Aim: There is no commercially available urinary cystatin-C (u-CYSC) test in the market. Therefore, we optimized and validated an automated immune turbidimetric test for u-CYSC measurements and investigated u-CYSC concentrations in acute and chronic diseases which might lead to renal tubular disorders. Materials & methods: A particle-enhanced immune turbidimetric assay was adapted and validated on a Cobas 8000/c502 analyzer. Urine samples of different patient groups were also analyzed. Results: Our method showed excellent analytical performance. U-CYSC/u-creatinine (u-CREAT) was higher in sepsis-related acute kidney injury group (p

Tanax(®) (T-61) is a euthanasia solution commonly used in veterinary medicine in Europe. It consists of three active components: embutramide, mebezonium iodide, and tetracaine hydrochloride. Human consumption of Tanax(®) (T-61) is usually associated with suicide attempts. In our 15-year-long practice, embutramide was detected only three times but within a short period. First, it was found in the urine of a 42-year-old veterinarian, and the other two observations were made in a 16-year-old young man. Urine samples were analyzed using Shimadzu Prominence TOX.I.S.II. HPLC-DAD system with online SPE extraction system. Both of the two patients denied any intention to die. These cases show that this veterinary drug may also be considered as potential drugs of abuse.

Background Studies showing the potential predictive value of the actin-binding protein gelsolin, in critically ill patients are scarce. Moreover, even up to now a rapid automated measurement of gelsolin has still remained a challenge. Therefore, we developed and validated an automated serum gelsolin immune turbidimetric assay for possible clinical use. Methods Validation of serum gelsolin assay was performed on a Cobas 8000/c502 analyzer (Roche) according to the second edition of Eurachem guidelines. Furthermore, we also studied the diagnostic value of serum gelsolin in sepsis when investigating sera of septic (n = 25), systemic inflammatory response syndrome (SIRS; n = 8) and control patients (n = 14). We compared our previously published Western blot data with those of the new turbidimetric assay. Results The sample volume was 7 μL and the assay time was 10 minutes. The detection limit was 0.72 mg/L, intra- and inter-assay imprecision remained in most cases less than 5% expressed as CV. Recovery was found to be 84.56%-93.52% and linearity study gave an appropriate correlation coefficient by linear regression analysis (r2 = .998). Septic patients exhibited lower (P = .015) first-day serum gelsolin levels than SIRS patients, which confirmed our previous Western blot results. The determined cut-off point for serum gelsolin was 14.05 mg/L (sensitivity: 75%; specificity: 60%) when investigating its diagnostic value in sepsis. Conclusion Based on the results, our immune turbidimetric measurement offers a rapid and accurate quantitation of gelsolin in human serum samples. Serum gelsolin seems a promising additional diagnostic marker of sepsis which has to be further investigated.

Papaver somniferum produces secondary metabolites which have important roles in self-defense processes, in plant biochemistry, and in allelochemistry. By performing experiments to determine how irregular stress effects changed the alkaloid content of poppies we have shown that different types of stress affect the quantities of alkaloids. Papaver somniferum (cv. ‘Kek Duna’, Budakalasz, Hungary) plants were grown for 2 months, from seeds, in quartz-sand (natural light, temperature 24–28°C, in Knopf ’s nutritive solution). In this work we studied alkaloids in poppies subjected to two kinds of stress — mycotoxin and drought. Amounts of alkaloids were measured by different separation and detection procedures — thin-layer chromatography (TLC and HPTLC) with fluorescence detection, and high-performance liquid chromatography (HPLC). HPLC proved superior for identification and approximate estimation of the morphine alkaloids, but the effects of stress on poppy plants can be detected by use of either method. Drough...

This study developed a selective and rapid high-performance liquid chromatography –diode array detection method for the confirmation of different cathinone derivates in human urine. Samples were prepared by solid-phase extraction (SPE) using procaine hydrochloride as the internal standard. The chromatographic separation was performed on a Kinetex PFP column using isocratic elution. The mobile phase was composed of a mixture of acetonitrile (33%, v/v) and 0.005M ammonium trifluoroacetate buffer (67%, v/v; pH 4.93+ 0.03) with a flow rate of 0.350 mL/min. The diode array detection was performed at 262 nm. The method was linear over the concentration range of 25–2,400 ng/mL. Intra-day and inter-day precision values for cathinones were less than 1.26% (relative standard deviation). The limit of detection for any compounds extracted from human urine by the optimized SPE method was 40 ng/mL and the limit of quantification was 100 ng/mL in the urine. The recovery rate of SPE was between 71 and 82% with a lower relative standard deviation than 2.35%.

Based on a four year leaf growth data-set we modelled the thermal time-dependent leaf ontogeny in upper and lower canopy layers of mature sessile oak trees, in a Quercetum petraeae-cerris forest stand (NE Hungary). Our regression models revealed no considerable differences between the timing of leaf unfolding and leaf expansion of different canopy layers. On the other hand seasonal course in leaf mass-to-area ratio (LMA) indicated that sun leaves needed considerably longer thermal time to fully develop their anatomical structures compared to shade leaves. LMA of sun leaves was higher during the whole leaf maturation process suggesting that 'sun' and 'shade' characteristics develop in very early stage of leaf ontogeny. Functioning of photosynthetic apparatus (Fv/Fo) in shade leaves have built up faster and performed better in all developmental stages which could be attributed to two main factors: 1) very early determination of leaf traits as a function of light environment and 2) evolving shading effect of upper canopy layer eliminates photoinhibition in lower leaves. leaf ontogeny / leaf traits / leaf morphology / chlorophyll fluorescence / light environment / Quercus petraea

The glycation of liver histones was studied in rats with streptozotocin-induced diabetes, in ethanol (EtOH)-treated rats, and in EtOH-treated diabetic rats. In diabetes, the conditions of glucose-protein addition are more favourable extracellularly in serum and in erythrocytes than in the nucleus. This is indicated by the increased level of serum fructosamine and by the high level of glycated haemoglobin, while the glycation of intracellular histone is decreased. In the serum of diabetic rats, we found a relatively high acetaldehyde level, which resulted in elevated histone fluorescence. Fluorescence is an accepted marker of advanced glycation end- product (AGE), the intensity of which, according to our experiments is related not to the level of serum glucose, but to the le vel of acetaldehyde. The data obtained with histone proteins in diabetic rats treated with EtOH are in good agreement with the results of our earlier in vitro experimental results obtained with H1 histone: the reaction of the two aldehydes (glucose and acetaldehyde) in combination gives a lower glycohistone value than they do separately.

2-(2-Furoyl)-5-(2-furanyl)-1H-imidazole (FFI) is detected in total histones and the lysine-rich histone 1 fraction isolated from calf thymus after in vitro glycation and hydrolysis with HCl, using gas chromatographic/mass spectrometric analysis. The finding suggests that glucose is bound to the epsilon-amino groups of the lysine residues of the histones. No FFI is monitored in native histone samples.

The time-course of the reaction of H1 and total histone with glucose, acetaldehyde or both has been studied using the NBT reduction test and fluorescence. With both methods, purified H1 histone gave higher absorbance with acetaldehyde than with a 1:1 combination of glucose and acetaldehyde. For total histone, the opposite was found; a 1:1 combination of the above two aldehydes had the higher absorbance. As an explanation, the possibility of different reactivity of the amino groups with glucose and acetaldehyde is proposed. A possible simultaneous interaction between glucose, acetaldehyde and serum protein, mainly albumin, may alter the results of the diagnostic protein glycation methods, e.g. of the fructosamine test, and, therefore, also the monitoring of diabetes.

Time course of glucose binding by histone Hl and total histones was followed in isolated histone preparations and in thymus nuclei. In both cases the uptake of glucose by Hl was surprisingly high in contrast to a much lower uptake of glucose by total histones. DNA is not implicated in glycation of histones in nuclei.

Summary Earlier examinations have shown that reducing sugars mainly react with the E-amino group of lysine. After DNA extraction, lysine-rich histone proteins of alcohol fixed nuclei of rat organs were treated with glucose-6-phosphate. It was possible to selectively stain the histone type proteins of DNA negative nuclei with basic dyes.

The effect of stress conditions on the concentrations of secondary metabolites were examined during various developmental stages of Papaver somniferum plants. P. somniferum plants were grown in laboratory conditions (Budakalász). The experiment consisted of 22 treatments. Significantly different alkaloid contents can be observed under different stress conditions. In general, the alkaloid contents of plants are very low; therefore, a highly sensitive and reliable method has to be developed for analysis. The amount of alkaloids was measured by 2 separation and detection techniques. Accuracy of the thin-layer chromatography method for quantitative analysis is limited. Without purification of samples the background is too noisy. Column liquid chromatography is a sensitive and relatively inexpensive method that allows precise quantitative determination of the alkaloid content.