Headspace analysis of E-cigarette fluids using comprehensive two dimensional GC×GC-TOF-MS reveals the presence of volatile and toxic compounds.

The analysis of electronic cigarrete (E-cigarette) fluids by high performance liquid chromatography or gas chromatography (GC) coupled to mass spectrometry (MS), GC hyphenated to flame-ionisation detection, or nuclear magnetic resonance spectroscopy poses many challenges due to the complex matrix and extremely high number of compounds present. In order to overcome these challenges, this study focused on the detection of the multiple complex compounds classes produced by the pyrolysis of E-cigarette liquids using comprehensive two dimensional gas chromatography (GCxGC) coupled to time of flight (TOF)-MS. Gas samples were prepared by heating E-liquids inside aluminium tins for 5 min. The tins were placed in a sand bath, which was temperature controlled at 200 °C. The samples were collected using thermal desorption tubes connected to volatile organic compound (VOC) sampling pump attached and subsequently analysed using GCxGC-TOF-MS. The greater peak resolution obtained when using GCxGC-TOF-MS allowed to distinguish many toxic compounds and VOCs that could not be detected by the other methods mentioned above. As a result, a comprehensive list of volatile compounds emitted from E-cigarette fluids when heated was established, which might allow a better understanding of potential health effects of vaping. Heating E-liquids to moderate temperature results in the emission of over 1000 volatile compounds of which over 150 are toxic. These compounds are either present in the liquid or can be formed during storage or heating leading to a more complex volatile profile of E-cigarette liquids than previously assumed. The application of GCxGC-TOF-MS allows the elucidation of this profile and therefore a better understanding of possible health implications.

Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life.

Thirdhand exposure to e-cigarette residue is likely to have harmful effects in children http://bit.ly/38a2umw.

Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy.

BACKGROUND CONTEXT: Neural compression associated with lumbar disc herniation is usually managed surgically by microdiscectomy. However, 10%-20% of patients re-present with debilitating back pain, and approximately 15% require further surgery. PURPOSE: Using an ovine model of microdiscectomy, the present study investigated the relative potential of pentosan polysulfate-primed mesenchymal progenitor cells (pMPCs) or MPC alone implanted into the lesion site to facilitate disc recovery. STUDY DESIGN: An ovine model of lumbar microdiscectomy was used to compare the relative outcomes of administering MPCs or pMPCs to the injury site postsurgery. METHODS: At baseline 3T magnetic resonance imaging (MRI) of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar disc levels. Sheep were randomized into three groups (n=6). The injured controls received no further treatment. Defects of the treated groups were implanted with a collagen sponge and MPC (5×105 cells) or pMPC (5×105 cells). After 6 months, 3T MRI and standard radiography were performed. Spinal columns were dissected, individual lumbar discs were sectioned horizontally, and nucleus pulposus (NP) and annulus fibrosus (AF) regions were assessed morphologically and histologically. The NP and AF tissues were dissected into six regions and analyzed biochemically for their proteoglycans (PGs), collagen, and DNA content. RESULTS: Both the MPC- and pMPC-injected groups exhibited less reduction in disc height (p<.05) and lower Pfirrmann grades (p≤.001) compared with the untreated injury controls, but morphologic scores for the pMPC-injected discs were lower (p<.05). The PG content of the AF injury site region (AF1) of pMPC discs was higher than MPC and injury control AF1 (p<.05). At the AF1 and contralateral AF2 regions, the DNA content of pMPC discs was significantly lower than injured control discs and MPC-injected discs. Histologic and birefringent microscopy revealed increased structural organization and reduced degeneration in pMPC discs compared with MPC and the injured controls. CONCLUSIONS: In an ovine model 6 months after administration of pMPCs to the injury site disc PG content and matrix organization were improved relative to controls, suggesting pMPCs' potential as a postsurgical adjunct for limiting progression of disc degeneration after microdiscectomy.

Dimethylsulfoniopropionate, superoxide dismutase and glutathione as stress response indicators in three corals under short-term hyposalinity stress.

Corals are among the most active producers of dimethylsulfoniopropionate (DMSP), a key molecule in marine sulfur cycling, yet the specific physiological role of DMSP in corals remains elusive. Here, we examine the oxidative stress response of three coral species (Acropora millepora, Stylophora pistillata and Pocillopora damicornis) and explore the antioxidant role of DMSP and its breakdown products under short-term hyposalinity stress. Symbiont photosynthetic activity declined with hyposalinity exposure in all three reef-building corals. This corresponded with the upregulation of superoxide dismutase and glutathione in the animal host of all three species. For the symbiont component, there were differences in antioxidant regulation, demonstrating differential responses to oxidative stress between the Symbiodinium subclades. Of the three coral species investigated, only A. millepora provided any evidence of the role of DMSP in the oxidative stress response. Our study reveals variability in antioxidant regulation in corals and highlights the influence life-history traits, and the subcladal differences can have on coral physiology. Our data expand on the emerging understanding of the role of DMSP in coral stress regulation and emphasizes the importance of exploring both the host and symbiont responses for defining the threshold of the coral holobiont to hyposalinity stress.

Evaluation of Novel Chalcone Oximes as Inhibitors of Tyrosinase and Melanin Formation in B16 Cells.

A series of hydroxy-substituted chalcone oxime derivatives were synthesized. These compounds were then evaluated for their inhibitory activities on tyrosinase and melanogenesis in murine B16F10 melanoma cells. The structures of the synthesized compounds were confirmed by (1) H NMR, (13) C NMR, FTIR, and HRMS. Two of the compounds exhibited much higher tyrosinase inhibitory activities (IC50 values of 4.77 and 7.89 µM, respectively) than the positive control, kojic acid (IC50 : 22.25 µM). Kinetic studies revealed them to act as competitive tyrosinase inhibitors with their Ki values of 5.25 and 8.33 µM, respectively. Both the compounds inhibited melanin production and tyrosinase activity in B16 cells. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues.

Development of hydroxylated naphthylchalcones as polyphenol oxidase inhibitors: Synthesis, biochemistry and molecular docking studies.

Polyphenol oxidase (Tyrosinase) has received great attention, since it is the key enzyme in melanin biosynthesis. In this study, novel hydroxy naphthylchalcone compounds were synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. The structures of the compounds synthesized were confirmed by (1)H NMR, (13)C NMR, FTIR and HRMS. Two of the compounds synthesized inhibited the diphenolase activity of tyrosinase in a dose dependent manner and exhibited much higher tyrosinase inhibitory activities (IC50 values of 10.4µM and 14.4µM, respectively) than the positive control, kojic acid (IC50: 27.5µM). Kinetic analysis showed that their inhibition was reversible. Both the novel compounds displayed competitive inhibition with their Ki values of 3.8µM and 4.5µM, respectively. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues. This study suggests hydroxy naphthylchalcone compounds to serve as promising candidates for use as depigmentation agents.

Design, synthesis and biological evaluation of hydroxy substituted amino chalcone compounds for antityrosinase activity in B16 cells.

A series of hydroxy substituted amino chalcone compounds have been synthesized. These compounds were then evaluated for their inhibitory activities on tyrosinase and melanogenesis in murine B16F10 melanoma cell lines. The structures of the compounds synthesized were confirmed by (1)H NMR, (13)C NMR, FTIR and HRMS. Two novel amino chalcone compounds exhibited higher tyrosinase inhibitory activities (IC50 values of 9.75µM and 7.82µM respectively) than the control kojic acid (IC50: 22.83µM). Kinetic studies revealed them to act as competitive tyrosinase inhibitors with their Ki values of 4.82µM and 1.89µM respectively. Both the compounds inhibited melanin production and tyrosinase activity in B16 cells. Docking results confirm that the active inhibitors strongly interact with mushroom tyrosinase residues. This study suggests that the depigmenting effect of novel amino chalcone compounds might be attributable to inhibition of tyrosinase activity, suggesting amino chalcones to be a promising candidate for use as depigmentation agents or as anti-browning food additives.

Azachalcones: a new class of potent polyphenol oxidase inhibitors.

A library of potent inhibitors of polyphenol oxidase and their structure activity relationships are described. Azachalcone derivatives were synthesized and tested for their tyrosinase inhibitory activity. Their inhibitory activities on mushroom tyrosinase using l-DOPA as a substrate were investigated. Two compounds that are the reduction congeners of the pyridinyl azachalcones strongly inhibited the enzyme activity and were more potent than the positive control kojic acid.

Pethidinic acid: corroboration of a doctor's denial of pethidine re-use.

Pethidine (meperidine), a synthetic opiate, formally used as an analgesic in surgery and obstetrics, has been an abused drug of choice for some doctors. A case is presented in which a doctor, who previously admitted to using pethidine, was suspected of re-using, following a second positive urine test. A laboratory had reported the presence of pethidine in the doctor's urine; however, the doctor denied re-use. The norpethidine (normeperidine) metabolite, normally found in urine, had not been detected, raising concern over the laboratory's conclusion and necessitating an independent investigation. Because the major metabolite of pethidine is pethidinic acid (meperidinic acid), accounting for approximately 40% of the excreted dose, its presence or absence were deemed to be important criteria in interpreting the laboratory result. Pethidinic acid was synthesized by alkaline hydrolysis of pethidine and used as a control. Urine samples from a patient receiving pethidine for pain, from the previous pethidine use of the doctor, and the urine under question plus the control were analyzed for the presence of pethidinic acid using electrospray mass spectrometry. Pethidinic acid was found in all samples except the one under dispute. The absence of pethidinic acid appeared to corroborate the doctor's denial of re-use.

Reactions of Pseudomonas aeruginosa pyocyanin with reduced glutathione.

Pseudomonas aeruginosa is the most common cause of chronic and recurrent lung infections in patients with cystic fibrosis (CF) whose sputa contain copious quantities of P. aeruginosa toxin, pyocyanin. Pyocyanin triggers tissue damage mainly by its redox cycling and induction of reactive oxygen species (ROS). The reactions between reduced glutathione (GSH) and pyocyanin were observed using absorption spectra from spectrophotometry and the reaction products analysed by nuclear magnetic resonance imaging. Pyocyanin reacted with GSH non-enzymatically at 37 degrees C resulting in the production of red-brown products, spectophotometrically visible as a 480 nm maximum absorption peak after 24 h of incubation. The reaction was concentration-dependent on reduced glutathione but not on pyocyanin. Minimizing the accessibility of oxygen to the reaction decreased its rate. The anti-oxidant enzyme catalase circumvented the reaction. Proton-NMR analysis demonstrated the persistence of the original aromatic ring and the methyl-group of pyocyanin in the red-brown products. Anti-oxidant agents having thiol groups produced similar spectophotometrically visible peaks. The presence of a previously unidentified non-enzymatic GSH-dependent metabolic pathway for pyocyanin has thus been identified. The reaction between pyocyanin and GSH is concentration-, time-, and O(2)-dependent. The formation of H(2)O(2) as an intermediate and the thiol group in GSH seem to be important in this reaction.