Trypanocidal activity of a new pterocarpan and other secondary metabolites of plants from Northeastern Brazil flora

Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora have been assayed against epimastigote forms of Trypanosoma cruzi, using the tetrazolium salt MTT as an alternative method. Eight compounds belonging to four different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed significant activity. Among them, a novel and a known pterocarpan, a chalcone, four withasteroids, and a meroterpene benzoquinone were the represented chemical classes.     

奥美拉唑联合法莫替丁治疗反流性食管炎的临床效果分析

目的：观察并分析奥关拉唑联合法莫替丁治疗反流性食管炎的临床效果。方法：选取2008年5月至2012年5月在本院确诊并治疗的反流性食管炎患者45例,随机平均分为三组。联合用药组（15例）：每日早餐前口服20mg奥关拉唑,睡前口服20mg法莫替丁;奥关拉唑组（15例）：每日口服两次奥美拉唑,每次20mg;法莫替丁组（15例）：每日口服两次法莫替丁,每次20mg。每组的治疗时间均为8周。在内镜指导下观察并比较三组患者的胸痛、反酸和烧心等主要病征的改善情况,综合评价三种治疗方法的临床疗效。结果：联合用药组较其他两组获得的疗效更明显,患者的症状得到较好的改善,差异有统计学意义（P〈0．05）。结论：奥美拉唑联合法莫替丁能够有效地抑制胃酸的分泌,对于反流性食管炎的,临床治疗具有良好的效果。     

Effect of temperature on seed production in the invasive grass Glyceria maxima (Hartm.) Holmb. (Poaceae) in South Africa

Temperature is one of the main factors that determine sexual reproduction in terrestrial and emergent aquatic plant species. The effect of temperature on sexual reproduction and seed production of Glyceria maxima (Hartm.) Holmb. in the southern hemisphere is unknown. Glyceria maxima collections in February 2010 at three isolated infestations in KwaZulu-Natal failed to yield a single seed, only empty panicles. Laboratory experiments showed that vernalisation had no consistent effect on seed production. Field- and laboratory-grown plants produced seeds in the 2010/2011 season, because of having sufficient time at optimum temperatures required for seed production (1 491 and 1 585 hours, respectively), compared to a shorter period (1 352 hours) of suitable temperatures during the 2009/2010 growing season. An inadequate period of optimum temperatures (15–25°C) during seed production resulted in the lack of seeds in the field in the 2009/2010 growing season. This study showed that temperature and duration of exposure thereto during the seed-production period play vital roles in G. maxima sexual reproduction.     

Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats

Background

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).

Methods

Celastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.

Results

Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.

Conclusions

Our results validate celastrol as a promising compound for the treatment of arthritis.     

Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55^Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4⁺ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P₂, therefore controlling Pr55^Gag membrane association. Rab27a also controls PI(4,5)P₂ levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55^Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P₂ production and, consequently, HIV-1 replication.     

Silence resulting from the cessation of movement signals danger

Most of what we know about the neural basis of fear has been unravelled by studies using associative fear learning [1]. However, many animal species are able to use social cues to recognize threats [2,3], a defence mechanism that may be less costly than learning from self-experience. Most studies in the field have focused on species-specific signals, such as alarm calls or pheromones, remaining unclear whether more generic cues can mediate this process. Here we report that rats perceive the cessation of movement-evoked sound as a signal of danger and its resumption as a signal of safety. To study transmission of fear between rats we assessed the behavior of an observer while witnessing a demonstrator cage-mate display fear responses. Having tested a multitude of cues, we found that observer rats respond to an auditory cue which signals the sudden immobility of the demonstrator rat - the cessation of the sound of motion. As freezing is a pervasive fear response in animals [4,5], silence may constitute a truly public cue used by a variety of animals in the ecosystem to detect impeding danger.     

Effects of immature cashew nut-shell liquid (Anacardium occidentale) against oxidative damage in Saccharomyces cerevisiae and inhibition of acetylcholinesterase activity

The cashew tree (Anacardium occidentale) represents one of the major cheapest sources of non-isoprenoid phenolic lipids, which have a variety of biological properties: they can act as molluscicides, insecticides, fungicides, have anti-termite properties, have medicinal applications, and demonstrate antioxidant activity in vitro. Immature cashew nut-shell liquid (iCNSL) is a unique natural source of unsaturated long-chain phenols. Their use has stimulated much research in order to prepare drug analogues for application in several fields. The objective of the present study was to determine whether iCNSL has antioxidant properties when used in strains of the yeast Saccharomyces cerevisiae and to measure the inhibitory activity of acetylcholinesterase. The constituents were identified using thin-layer chromatography, gas chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and (1)H and (13)C nuclear magnetic resonance. The iCNSL contains anacardic acid, cardanol, cardol, and 2-methyl cardol. Immature cashew nut oil contains triacylglycerols, fatty acids, alkyl-substituted phenols, and cholesterol. The main constituents of the free fatty acids are palmitic (C(16:0)) and oleic acid (C(18:1)). iCNSL has excellent protective activities in strains of S. cerevisiae against oxidative damage induced by hydrogen peroxide and inhibits acetylcholinesterase activity. iCNSL may have an important role in protecting DNA against damage induced by reactive oxygen species, as well as hydrogen peroxide, generated by intra- and extracellular mechanisms.     

Coccolithus pelagicus, a productivity proxy related to moderate fronts off Western Iberia

The traditional interpretation of Coccolithus pelagicus as a cold water proxy is examined based on its distribution patterns in the water column off the Portuguese coast (using data from eleven cruises) and in Holocene surface sediment samples and Quaternary cores from the same region.Coccolithus pelagicus is common in the Portuguese upwelling system, an area where surface waters are predominantly of subtropical origin. Although revealing an affinity for low temperature upwelled waters, the species was found in waters up to 18°C associated with riverine plume and shelf-break fronts. C. pelagicus seemed to consistently occupy a particular ecological niche, between other phytoplankton groups, related to moderate turbulence conditions combined with nutrient availability. From this behaviour, it is proposed that C. pelagicus can be used as a tracer of the periphery of areas of enhanced productivity.Coccolithus pelagicus preferences for fronts of moderate temperature and salinity gradients are tentatively used to explain particular features of its sedimentary record. The repeated increase of C. pelagicus in thanatocoenoses (surface sediment assemblages) close to three river mouths, on the Portuguese shelf, are interpreted as a positive response to the development of riverine plumes. On the other hand, inconsistencies in the correlation between sea surface cooler-glacial and warmer-interglacial isotope stages and the relative abundance pattern of C. pelagicus during the Late Quaternary, as registered in two Galicia Bank piston cores (42°N), are tentatively explained in terms of shifts in the extent of the outer limit of the local palaeoproductivity belt off the Iberian Peninsula.