Gas-phase fragmentation of protonated piplartine and its fungal metabolites using tandem mass spectrometry and computational chemistry.

Piplartine, an alkaloid produced by plants in the genus Piper, displays promising anticancer activity. Understanding the gas-phase fragmentation of piplartine by electrospray ionization tandem mass spectrometry can be a useful tool to characterize biotransformed compounds produced by in vitro and in vivo metabolism studies. As part of our efforts to understand natural product fragmentation in electrospray ionization tandem mass spectrometry, the gas-phase fragmentation of piplartine and its two metabolites 3,4-dihydropiplartine and 8,9-dihydropiplartine, produced by the endophytic fungus Penicillium crustosum VR4 biotransformation, were systematically investigated. Proposed fragmentation reactions were supported by ESI-MS/MS data and computational thermochemistry. Cleavage of the C-7 and N-amide bond, followed by the formation of an acylium ion, were characteristic fragmentation reactions of piplartine and its analogs. The production of the acylium ion was followed by three consecutive and competitive reactions that involved methyl and methoxyl radical eliminations and neutral CO elimination, followed by the formation of a four-member ring with a stabilized tertiary carbocation. The absence of a double bond between carbons C-8 and C-9 in 8,9-dihydropiplartine destabilized the acylium ion and resulted in a fragmentation pathway not observed for piplartine and 3,4-dihydropiplartine. These results contribute to the further understanding of alkaloid gas-phase fragmentation and the future identification of piplartine metabolites and analogs using tandem mass spectrometry techniques. Copyright © 2017 John Wiley & Sons, Ltd.

A simple flash sintering setup under applied mechanical stress and controlled atmosphere.

UNLABELLED: Most flash sintering experimental set-ups use dog bone-shaped specimen and DC current, which results in heterogeneously distributed densification and grain growth throughout the sample. This is the reason why only the sample's core characteristics after flash are taken into account. On the other hand, some recent procedures suggest the use of cylindrical pellets, which have some advantages compared to the traditional mode as the use of easily conformed samples and its final uniformity. Our new experimental set-up offers the possibility of atmosphere control and pressure application. Also the electrodes material change can be easily made when necessary. Shrinkage measurements and impedance spectroscopy are realized in situ and experimental parameters, as oven heating for example, can be varied to control microstructure changes. ADVANTAGES: •Sample can be entirely recovered at the end of the experiment and can be analyzed throughout its entire extension, including regions in contact with the electrodes that may present some differences from pellets inner part.•The use of AC current enables the study of different frequencies effects.•Experimental set-up can be adapted to different kinds of electrolytes (samples), easily changing electrode's material and atmosphere.

The influence of fixed orthodontic appliances on masticatory and swallowing threshold performances.

To test the hypothesis that treatment with orthodontic appliances disturbs masticatory and swallowing performances. Twenty-seven subjects with malocclusions requiring orthodontic treatment were included in this prospective study. The masticatory and swallowing performances were evaluated at five different times: before bracket placement (T0), immediately after archwire placement (T1), 48 h after archwire placement (T2), 30 days after archwire placement (T3) and 3 months after the initial appointment (T4). Masticatory performance was determined by the median particle sizes for the Optocal test food after 15 chewing strokes, and the swallowing thresholds were registered for both the test food and a natural food (peanuts). Pain during mastication was evaluated using a 100-mm visual analogue scale. Masticatory performance was significantly reduced at T2, at which time patients reported the highest pain values. The time spent to the first swallow was increased at T2 for the natural food but not for the test food. The values for pain, masticatory and swallowing performances at T3 and T4 were similar to those at T0. Orthodontic patient masticatory function is only reduced during the period of higher pain experience, which could also disrupt the deglutition of harder foods. However, neither mastication nor deglutition processes were disturbed by orthodontic appliances in long-term treatment.

Effects of chlorogenic acid on neutrophil locomotion functions in response to inflammatory stimulus.

AIM OF THE STUDY: Species of Lychnophora are used in Brazilian folk medicine as analgesic and anti-inflammatory agents. Chlorogenic acid (CGA) and their analogues are important components of polar extracts of these species, as well in several European and Asian medicinal plants. Some of these phenolic compounds display anti-inflammatory effects. In this paper we report the isolation of CGA from Lychnophora salicifolia and its effects on functions involved in neutrophils locomotion. MATERIALS AND METHODS: LC-MS(n) data confirmed the presence of CGA in the plant. Actions of CGA were investigated on neutrophils obtained from peritoneal cavity of Wistar rats (4h after 1% oyster glycogen solution injection; 10 ml), and incubated with vehicle or with 50, 100 or 1000 µM CGA in presence of lipopolysaccharide from Escherichia coli (LPS, 5 µg/ml). Nitric oxide (NO; Griess reaction); prostaglandin E(2) (PGE(2)), interleukin-1ß (IL-1ß) and tumor necrosis factor-α [TNF-α; enzyme-linked immunosorbent assay (EIA)]; protein (flow cytometry) and gene (RT-PCR) expression of L-selectin, ß(2)integrin and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were quantified. In vitro neutrophil adhesion to primary culture of microvascular endothelial cell (PMEC) and neutrophil migration in response to formyl-methionil-leucil-phenilalanine (fMLP, 10(-8)M, Boyden chamber) was determined. RESULTS: CGA treatment did not modify the secretion of inflammatory mediators, but inhibited L-selectin cleavage and reduced ß(2) integrin, independently from its mRNA synthesis, and reduced membrane PECAM-1 expression; inhibited neutrophil adhesion and neutrophil migration induced by fMLP. CONCLUSIONS: Based on these findings, we highlight the direct inhibitory actions of CGA on adhesive and locomotion properties of neutrophils, which may contribute to its anti-inflammatory effects and help to explain the use of Lychnophora salicifolia as an anti-inflammatory agent.

Structural and magnetic properties of pure and nickel doped SnO2 nanoparticles.

Ni-doped SnO2 nanoparticles prepared by a polymer precursor method have been characterized structurally and magnetically. Ni doping (up to 10 mol%) does not significantly affect the crystalline structure of SnO2, but stabilizes smaller particles as the Ni content is increased. A notable solid solution regime up to ∼ 3 mol% of Ni, and a Ni surface enrichment for the higher Ni contents are found. The room temperature ferromagnetism with saturation magnetization (MS) ∼ 1.2 × 10 (- 3) emu g (- 1) and coercive field (HC) ∼ 40 Oe is determined for the undoped sample, which is associated with the exchange coupling of the spins of electrons trapped in oxygen vacancies, mainly located on the surface of the particles. This ferromagnetism is enhanced as the Ni content increases up to ∼ 3 mol%, where the Ni ions are distributed in a solid solution. Above this Ni content, the ferromagnetism rapidly decays and a paramagnetic behavior is observed. This finding is assigned to the increasing segregation of Ni ions (likely formed by interstitials Ni ions and nearby substitutional sites) on the particle surface, which modifies the magnetic behavior by reducing the available oxygen vacancies and/or the free electrons and favoring paramagnetic behavior.

[Occurrence of meningococcal meningitis in a Southern region of Brazil, from 1974 to 1980, using the point event model]. / Estudo da ocorrência de meningite meningocócica em região meridional do Brasil, de 1974 a 1980, utilizando o modelo ponto evento.

Descriptive statistical techniques and point event model methods were used to investigate the temporal series of cases of meningococcal meningitis which occurred in 100 municipalities in the Rio Grande do Sul State, Brazil, during the period 1974-1980. The data were grouped by epidemiological state (epidemic or endemic), and separated into 5 groups according to the municipal population. The number of cases of the disease notified weekly was analysed by means of incidence coefficients, with the purpose of studying the epidemic threshold for the state. The time interval between events was analysed in the light of their probability density functions and expected density functions, with the objective of studying the relationship and dependences among events. The analysis of the epidemic threshold suggests that there should not be only one threshold value for detection of outbreak of the disease throughout the state. Analysis of the expected density function extracted from inter-event intervals of the epidemic state showed a correlational structure indicating dependence between events occurring up to 14 weeks apart. No significant correlation for the endemic state, taking as reference model the shuffled version of the original intervals, was observed.