Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats

Prenatal stress (PNS) impairs the circadian rhythm of the sleep/wake cycle. The melatonin (MT) analogue Piromelatine (Pir) was designed for the treatment of insomnia. The present study aimed to explore effects of Pir on circadian rhythmicity, motor activity, and sleep structure in male and female rats with a history of prenatal stress (PNS). In addition, we elucidated the role of MT receptors and brain-derived neurotrophic factor (BDNF) to ascertain the underlying mechanism of the drug. Pregnant rats were exposed to different stressors from day seven until birth. Piromelatine (20 mg/kg/day/14 days) was administered to young adult offspring. Home-cage locomotion, electroencephalographic (EEG) and electromyographic (EMG) recordings were conducted for 24 h. Offspring treated with vehicle showed sex-and phase-dependent disturbed circadian rhythm of motor activity and sleep/wake cycle accompanied by elevated rapid eye movement (REM) pattern and theta power and diminished non-rapid eye movement (NREM) sleep and delta power. While Pir corrected the PNS-induced impaired sleep patterns, the MT receptor antagonist luzindol suppressed its effects in male and female offspring. In addition, Pir increased the BDNF expression in the hippocampus in male and female offspring with PNS. Our findings suggest that the beneficial effect of Pir on PNS-induced impairment of sleep/wake cycle circadian rhythm and sleep structure is exerted via activation of MT receptors and enhanced BDNF expression in the hippocampus in male and female offspring.     

SLC38A4 Amino Acid Transporter Expression Is Significantly Lower in Early Preterm Intrauterine Growth Restriction Complicated Placentas

Intrauterine growth restriction (IUGR), predominantly caused by placental insufficiency, affects partitioning of nutrients to the fetus. The system A sodium-coupled transporters (SNAT or SLC38), of types A1, A2, and A4, control non-essential amino acid uptake and supply. Here, we aimed to investigate the expression of these transporters across different placental disease cohorts and cells. To determine disease impact, transporter expressions at the gene (qPCR) and protein (western blots) level were assessed in gestationally matched placental tissues. Early (<34 weeks), and late (34–36 weeks) onset IUGR cases with/out preeclampsia were compared to preterm controls. We also investigated level of transporter expression in primary trophoblasts under glucose deprivation (n = 6) and hypoxia conditions (n = 7). SLC38A4 protein was significantly downregulated in early preterm pregnancies complicated with IUGR with/out preeclampsia. There were no differences in late preterm IUGR cohorts. Furthermore, we demonstrate for the first time in primary trophoblast cells, that gene expression of the transporters was sensitive to and induced by glucose starvation. SLC38A4 mRNA expression was also significantly upregulated in response to hypoxia. Thus, SLC38A4 expression was persistently low in early preterm IUGR pregnancies, regardless of disease aetiology. This suggests that gestational age at delivery, and consequently IUGR severity, may influence loss of its expression.     

Reducing methyl eugenol content in <Emphasis Type="Italic">Rosa damascena Mill</Emphasis> rose oil by changing the traditional rose flower harvesting practices

Methyl eugenol (ME) is a naturally occurring carcinogenic compound found in a number of essential oils including rose oil distilled from Rosa damascena Mill flowers. In the current study, we evaluate the effect of flower harvesting practices on the ME content in the produced rose oil. The obtained results show nearly twice reduction in ME content in the rose oil distilled from petals of full-blown flowers. At the same time, GC/MS analysis of rose oils distilled from stages 3 and 4 rose flower buds (flower buds prior opening of petals) showed more than 5 times ME reduction and preservation of the relative content of the major rose oil compounds. Moreover, the comparative study of rose flower yield and rose oil content of rose buds and full-blown flowers showed that harvesting of rose flower buds results in above three times increase in the formed flower buds from the studied rose plants and more than twice increase in the rose flower and rose oil yields for the same rose plantation areas. The overall results from this study allow us to propose a change in the traditional full-blown rose flower harvesting to harvesting of rose flower buds at stages 3 and 4 during the entire flowering period.     

Synthesis and evaluation of anticancer natural product analogues based on angelmarin: targeting the tolerance towards nutrient deprivation

Inspired by nature: Angelmarin is an anticancer natural product with potent antiausterity activity, that is, selective cytotoxicity towards nutrient-deprived, resistant cancer cells. Through structure-activity relationship studies, three analogues were identified as lead compounds for the develpoment of molecular probes for the investigation of the mode of action and biological targets of the antiausterity compounds.     

PARTICLE SIZE,SOLVENT, OXYGEN,TEMPERATURE AND PRESSURE EFFECTS ON THE CONTENTS OF INSOLUBLE FRACTIONS FROM SOLID VACUUM RESIDUA

ABSTRACT

n-Heptane insoluble contents were determined for an extraheavy-oil vacuum residue, one petroleum and one coal pitch as a function of particle size. This variable was found to affect the yields of insoluble material, aspect which was also observed during extractions carried out with aromatic and halogenated solvents. The precision of results was observed to be independent on the operators. A study was carried out to determine the effect of sample drying time on fraction yields. It was found that maltene fractions were strongly dependent on this variable, whereas asphaltene fractions were totally independent

Predissolution in aromatic solvents proved worthless from the repeatability point of view. However, predissolution of the oil residue in CH₂Cl₂ followed by filtration and asphaltene precipitation with simultaneous solvent removal, was deemed to be a suitable technique to remove mineral matter and isolate asphaltenes in a single step

Sample oxidation during asphaltene precipitation and isolation was detected by gravimetric and spectroscopic techniques. This fact is very important since common precipitation techniques do not address this issue

Preliminary accelerated extraction experiments carried out with pitch samples at high temperature and pressure, revealed that this approach can be a very interesting research tool to investigate solubility properties.     

Novel Use of Scanning Electron Microscopy for Detection of Iron‐Induced Morphological Changes in Human Blood

Fibrinogen is key to the maintenance of hemostasis and is an acute phase protein that is part of the coagulation cascade of proteins. It plays a fundamental role in inflammation, particularly as indicator for a proinflammatory state and is a prominent marker for developing vascular inflammatory diseases. The ultrastructure of fibrin nets can be studied using scanning electron microscopy (SEM) with the addition of thrombin to plasma. In inflammatory conditions such as thromboembolic ischemic stroke and diabetes, the fibrin networks are changed to from dense matted fibrin deposits (DMDs) instead of typical netlike appearance. Similar DMDs can also be induced with the addition of FeCl₂ and FeCl₃. Importantly, the iron‐induced DMDs look similar to those from patients with prothrombotic conditions. Excessive or misplaced tissue iron now is recognized to pose a substantial health risk. The current research therefore investigates the establishment of a laboratory fibrinogen model to study that might mimic fibrin fiber generation that is achieved using plasma from healthy and diseased individuals. Furthermore, to determine whether the addition of iron to purified fibrinogen will show DMDs and whether hydrophilic agents can prevent them. We conclude that SEM is a very effective tool for the visualization of circulatory consequences of the interaction of iron‐induced hydroxyl radicals with human fibrinogen. Furthermore, this novel fibrinogen model provides a convenient method to study the interactions of the intramolecular and intermolecular hydrophobic forces responsible for the maintenance of the tertiary structure of native fibrin(ogen) and the prevention of iron‐induced DMDs formation by hydrophilic agents. Microsc. Res. Tech. 76:268–271, 2013. © 2012 Wiley Periodicals, Inc.     

Performance of fluorene and terthiophene copolymer in bilayer photovoltaic devices: The role of the polymer conformations

We report experiments using fluorene and terthiophene copolymer as the active layer in bilayer devices with C₆₀. The highest short circuit current, open circuit voltage and power conversion efficiency upon AM1.5 illumination were 6.8 mA/cm², 0.68 V and 2.33%, respectively. Density functional theory analysis was used to identify the most stable configurations of the terthiophene moieties in the polymer: the most stable form has the thiophene rings in the alternate configuration (anti) and the second conformation has the thiophene rings pointing to the same direction (syn). Comparing theoretical results with measurements of absorbance, X-ray diffraction, and X-ray reflectometry experiments, we conclude that the annealing treatment produces conformational anti to syn transition along the backbone of poly[9,9′-n-dihexyl-2,7-fluorene-alt-2,5-terthiophene] (LaPPS45). The syn segments of the chain condensed then in a lamellar ordered structure which increases the degree of crystallinity of the annealed samples and improve the light harvest at long wavelengths. From absorption measurements of films submitted to different annealing temperatures and with the help of theoretical calculations we propose a “wave-like” aggregation pattern to the syn segments in those lamellas.