A new analytical method for determination of coenzyme Q10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CoQ10) in human plasma was developed based on CE using a double tensioactive microemulsion. CoQ10 was quantitatively extracted into 1-propanol/hexane and quantified by MEEKC. The microemulsion was prepared by mixing 1.4% w/w sodium bis(2-ethylhexyl) sulfosuccinate, 4% w/w cholic acid, 1% w/w octane, 8.5% w/w butanol, 0.1% w/w PVA and 85% w/w 10 mM Tris buffer at pH 9.0. The optimized electrophoretic conditions included the use of an uncoated silica capillary of 60 cm total length and 75 mum id, an applied voltage of 20 kV, room temperature and 214 nm ultraviolet detection. Selectivity, linearity, LOD, LOQ, precision and accuracy were evaluated as the parameters of validation. Owing to its simplicity and reliability, the proposed method can be an advantageous alternative to the traditional methodology for the quantitation of CoQ10 in human plasma with good accuracy and precision.

Background: The diagnosis and treatment of intrahepatic cholestasis of pregnancy (ICP) has important implications on fetal health. The biochemical parameter commonly used in the diagnosis of ICP is the determination of the concentration of total serum bile acids (TSBA). However, bile acid profile, especially lithocholic acid (LCA) analysis is a more sensitive and specific biomarker for differential diagnosis of this pathology and also could be an alternative to evaluate the efficiency of ursodeoxycholic acid (UDCA) for ICP treatment. Methods: Serum bile acid (SBA) profiles including LCA determination, were studied in 28 ICP patients using a capillary electrophoresis method. The effects of UDCA treatment on bile acid profile, were analysed in 23 out of 28 ICP patients and the two samples obtained before and 15 days after treatment were compared. Two samples taken as controls were also obtained from each of five patients without therapy. Results: A dramatic decrease in LCA concentrations and maintenance of TSBA concentrations were found in all patients after UDCA therapy, whereas SBA profiles together with LCA values did not change in patients without therapy. Conclusion: We propose LCA as an alternative biomarker and a more sensitive parameter than TSBA to evaluate the effectiveness of UDCA treatment, at least in ICP patients from Argentina.

An abrupt increase in metastatic growth as a consequence of the removal of primary tumors suggests that the concomitant resistance (CR) phenomenon might occur in human cancer. CR occurs in murine tumors and ROS-damaged phenylalanine, meta-tyrosine (m-Tyr), was proposed as the serum anti-tumor factor primarily responsible for CR. Herein, we demonstrate for the first time that CR happens in different experimental human solid tumors (prostate, lung anaplastic, and nasopharyngeal carcinoma). Moreover, m-Tyr was detected in the serum of mice bearing prostate cancer (PCa) xenografts. Primary tumor growth was inhibited in animals injected with m-Tyr. Further, the CR phenomenon was reversed when secondary implants were injected into mice with phenylalanine (Phe), a protective amino acid highly present in primary tumors. PCa cells exposed to m-Tyr in vitro showed reduced cell viability, downregulated NFκB/STAT3/Notch axis, and induced autophagy; effects reversed by Phe. Strikingly, m-Tyr administration also impaired both, spontaneous metastasis derived from murine mammary carcinomas (4T1, C7HI, and LMM3) and PCa experimental metastases. Altogether, our findings propose m-Tyr delivery as a novel approach to boost the therapeutic efficacy of the current treatment for metastasis preventing the escape from tumor dormancy.

Until now, biochemical parameter for diagnosis of intrahepatic cholestasis of pregnancy (ICP) mostly used is the rise of total serum bile acids (TSBA) above the upper normal limit of 11 μM. However, differential diagnosis is very difficult since overlapped values calculated on bile acids determinations, are observed in different conditions of pregnancy including the benign condition of pruritus gravidarum. The aim of this work was to determine the better markers in ICP for a precise diagnosis together with parameters associated with severity of symptoms and treatment evaluation. Serum bile acid profiles were evaluated using capillary electrophoresis in 38 healthy pregnant women and 32 ICP patients and it was calculated the sensitivity, specificity, accuracy, predictive values and the relationships of certain individual bile acids in pregnant women in order to replace TSBA determinations. The evaluation of the results shows that LCA and UDCA/LCA ratio provided information for a more complete and accurate diagnosis and evaluation of ICP than calculation of solely TSBA levels in pregnant women.

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A new CE system based on the use of polymeric-mixed micelles (cholic acid, SDS and the poloxamine Tetronic(®) 1107) was developed for the simultaneous determination of nine steroids in human urine. This method allows the baseline separation and quantitation of cortisol, androstenedione, estriol, dehydroepiandrosterone sulfate, testosterone, dehydroepiandrosterone, estrone, progesterone and estradiol in less than 25 min showing to be sensitive enough to detect low concentrations of these steroids in urine samples (5-45 ng/mL). The optimized electrophoretic conditions were performed using a 50 cm × 75 μm capillary, 18 kV, 25°C, with 44 mM cholic acid, 10 mM SDS, 0.05% w/v tetronic(®) 1107, 2.5% v/v methanol, 2.5% v/v tetrahydrofuran in 5 mM borate - 5 mM phosphate buffer (pH=8.0) as a background electrolyte and a dual 210/254 UV-detection. The method can simultaneously determine 0.1-120 μg/mL, which corresponds to 5-6000 ng/mL of steroids in 2 mL urine. The recoveries ranged between 82.4 and 101.5%. Due to its simplicity, speed, accuracy and reliability, the proposed method could be a potential alternative to the traditional methodologies used with clinical purposes.

Brown carbon (BrC) is involved in atmospheric light absorption and climate forcing and can cause adverse health effects. Understanding the formation mechanisms and molecular structure of BrC is of key importance in developing strategies to control its environment and health impact. Structure determination of BrC is challenging, due to the lack of experiments providing molecular fingerprints and the sheer number of molecular candidates with identical mass. Suggestions based on chemical intuition are prone to errors due to the inherent bias. We present an unbiased algorithm, using graph-based molecule generation and machine learning, which can identify all molecular structures of compounds involved in biomass burning and the composition of BrC. We apply this algorithm to C12H12O7, a light-absorbing “test case” molecule identified in chamber experiments on the aqueous photo-oxidation of syringol, a prevalent marker in wood smoke. Of the 260 million molecular graphs, the algorithm leaves only 36,518 (0.01%) as viable candidates matching the spectrum. Although no unique molecular structure is obtained from only a chemical formula and a UV/vis absorption spectrum, we discuss further reduction strategies and their efficacy. With additional data, the method can potentially more rapidly identify isomers extracted from lab and field aerosol particles without introducing human bias.