Amino Acid Profiling of Follicular Fluid in Assisted Reproduction Reveals Important Roles of Several Amino Acids in Patients with Insulin Resistance.

The global prevalence of insulin resistance (IR) is increasing continuously, influencing metabolic parameters and fertility. The metabolic changes due to IR can alter the molecular composition of plasma and other body fluids. Follicular fluid (FF) is derived mainly from plasma, and it is a critical microenvironment for the developing oocytes. It contains various metabolites and amino acids, and the quality of the oocytes is linked at least partially to amino acid metabolism. Our goal was to quantitatively determine the amino acid (AA) profile of FF in IVF patients and to compare IR and non-insulin resistance (NIR) groups to investigate the AA changes in their FF. Using UHPLC-based methods, we quantified the main 20 amino acids from human FF samples in the IR and NIR groups. Several amino acids (aspartate, glycine, glutamate, and cysteine) differed significantly (p < 0.05 or less) between the two groups. The most significant alterations between the IR and NIR groups were related to the glutathione metabolic pathway involving glycine, serine, and threonine. Since insulin resistance alters the amino acid composition of the FF, the oocytes may undergo metabolism-induced changes resulting in poor oocyte quality and less fertility in the insulin resistance groups.

[Childhood sporadic type of hemiplegic migraine with arteria cerebri media hypoperfusion]. / Gyermekkori sporadikus hemiplegiás migrén arteria cerebri media hipoperfúzióval.

Hemiplegic migraine is a rare subtype of migraine that is associated with reversible motor weakness in the aura phase. This is an uncommon form of migraine usually starting in childhood. The purpose of this case report is to highlight the differential diagnostic difficulty of the first attack. We describe a case, where the fluctuating unilateral motor weakness and aphasia suggested that the patient had ischaemic stroke. Nevertheless the brain MRI and MR angiography, the measured 5-hydroxyindole acetic acid (5-HIAA) concentration changes and the spontaneously improving clinical status proved the diagnosis of hemiplegic migraine. The MRI and MR angiography was very beneficial in establishing the correct diagnosis in this case. To distinguish between the familiar and sporadic type of hemiplegic migraine further genetic tests can be carried out.

Plasma Levels and Renal Handling of Amino Acids Contribute to Determination of Risk of Mortality or Feed of Ventilation in Patients with COVID-19.

COVID-19 infection may lead to serious complications, e.g., need for mechanical ventilation or death in some cases. A retrospective analysis of patients referred to our COVID Emergency Department, indiscriminately, was performed. A routine lab analysis measured amino acids in plasma and urine of patients. Data of surviving and deceased patients and those requiring or not requiring mechanical ventilation were compared, and logistic regression analyses have been performed. Deceased patients were older, had higher blood glucose, potassium, AST, LDH, troponin, d-dimer, hsCRP, procalcitonin, interleukin-6 levels (p < 0.05 for all). They had lower plasma serine, glycine, threonine, tryptophan levels (p < 0.01), higher tyrosine and phenylalanine levels (p < 0.05), and higher fractional excretion of arginine, methionine, and proline (p < 0.05) than survivors. In a regression model, age, severity score of COVID-pneumonia, plasma levels of threonine and phenylalanine were predictors of in-hospital mortality. There was a difference in ventilated vs. non-ventilated patients in CT-scores, glucose, and renal function (p < 0.001). Using logistic regression, CT-score, troponin, plasma level, and fractional excretion of glycine were predictors of ventilation. Plasma levels and renal excretion of certain amino acids are associated with the outcome of COVID-19 infection beside other parameters such as the CT-score or age.

New psychoactive versus conventional stimulants - a ten-year review of casework in Hungary.

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 Pécs, 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 (262), mephedrone (188), N-ethylhexedrone (126), 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.

Embutramide, a Component of Tanax(®) (T-61) as a New Drug of Abuse?

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.

Simultaneous determination of 4-substituted cathinones (4-MMC, 4-MEC and 4-FMC) in human urine by HPLC-DAD.

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%.