A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia

A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F_2t-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D₃ in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D₃ hydroxylations and progesterone synthesis, we propose that Vitamin D₃ might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D₃ supplementation in prevention and treatment of preeclampsia.     

Individual and Combined Treatments with Methylated Resveratrol Analogue DMU-214 and Gefitinib Inhibit Tongue Cancer Cells Growth via Apoptosis Induction and EGFR Inhibition

The methylated resveratrol analogue 3′-hydroxy-3,4,5,4′-tetramethoxystilbene (DMU-214) has been revealed to exert the anti-cancer activity by a block of the cell cycle at the G2/M phase, apoptosis induction, and metastasis inhibition. These biological events may be involved in crosstalk with the epidermal growth factor receptor (EGFR), which belongs to the ErbB family of receptor tyrosine kinases. Several cancer therapeutic approaches employ small molecules capable of inhibiting tyrosine kinases (e.g., gefitinib). According to more recent reports, combining gefitinib with chemotherapeutics, such as cisplatin, seems to be more effective than monotherapy. The present study aimed to assess the molecular mechanism of the potential anti-proliferative activity of individual and combined treatments with DMU-214 and gefitinib in SCC-25 and CAL-27 human tongue cancer cell lines. We showed for the first time the anti-cancer effects of DMU-214, gefitinib, and their combination in tongue cancer cells triggered via cell cycle arrest, apoptosis induction, and inhibition of the EGFR signaling pathway. The anti-proliferative effects of DMU-214 and gefitinib are also suggested to be related to the EGFR and EGFRP (phosphorylated epidermal growth factor receptor) expression status since we found significantly weaker cytotoxic activity of the compounds tested in SCC-25 cells, which overexpressed EGFR and EGFRP proteins.     

The effect of sample storage and homogenisation techniques on the chemical composition and near infrared spectra of white grapes

The effect of sample freezing, speed of homogenisation, time of homogenisation and homogeniser type on the chemical composition and near infrared (NIR) spectra of white grape berry samples has been examined. Samples of Chardonnay and Riesling sourced from South Australia were homogenised fresh and after different period of frozen storage (overnight, or 1, 2, 3 and 10 weeks) using a Retsch homogeniser or Waring blender. Two speeds (high and low) and two time intervals (20 and 60 s) were applied for samples homogenised with the Waring blender. All samples were analysed immediately after homogenisation by chemical and NIR analysis. The results showed that neither short time freezing nor prolonged frozen storage had any influence on TSS concentration and pH. However a significant increase in concentration of total phenolics was observed in samples after freezing and frozen storage. With the Waring blender, speed and time influenced total phenolics measurement. There was also an effect observed on the NIR spectra of the samples due to different speed and time of homogenisation.     

Inhibition of activity of urease in native form and immobilized on chitosan membrane by sodium fluoride

The influence of sodium fluoride inhibitor on the activity of urease in native form and immobilized covalently on glutaraldehyde-pretreated chitosan membrane was studied. Initially, in the presence of fluoride ions (I), a complex EI is formed which undergoes slow isomerization into a secondary form EI*. Both stages are represented on the progress curves. The dissociation constant of EI, K_i, for native and bonded urease were determined. The apparent rate constant as a function of the initial urea concentration for a given fluoride ion concentration was calculated, k = k ([I], [S]). It was found that sodium fluoride is a competitive slow-binding inhibitor of urease. Hydrolysis of urea in the standard conditions, at pH = 7.0, at 25° and a constant ionic strength and variable concentrations of substrate and of inhibitor has been studied. The reaction was initiated by addition of enzyme and was observed over a period of 10 min. The rate of hydrolysis at any point of time for both forms of urease, free and bound, may be calculated from the inhibition constants K_i, K*_i and apparent rate constant, k. It was found that immobilized urease is more resistant to the action of the inhibitor than the native one. This property offers potential for practical application.     

Effects of Endurance Training on the Coenzyme Q Redox State in Rat Heart,Liver, and Brain at the Tissue and Mitochondrial Levels: Implications for Reactive Oxygen Species Formation and Respiratory Chain Remodeling

Sixteen adult, 4-month-old male Wistar rats were randomly assigned to the training group (n = 8) or the control group (n = 8). We elucidated the effects of 8 weeks of endurance training on coenzyme Q (Q) content and the formation of reactive oxygen species (ROS) at the tissue level and in isolated mitochondria of the rat heart, liver and brain. We demonstrated that endurance training enhanced mitochondrial biogenesis in all tested organs, while a significant increase in the Q redox state was observed in the heart and brain, indicating an elevated level of QH₂ as an antioxidant. Moreover, endurance training increased the mQH₂ antioxidant pool in the mitochondria of the heart and liver, but not in the brain. At the tissue and isolated mitochondria level, an increase in ROS formation was only observed in the heart. ROS formation observed in the mitochondria of individual rat tissues after training may be associated with changes in the activity/amount of individual components of the oxidative phosphorylation system and its molecular organization, as well as with the size of the oxidized pool of mitochondrial Q acting as an electron carrier in the respiratory chain. Our results indicate that tissue-dependent changes induced by endurance training in the cellular and mitochondrial QH₂ pool acting as an antioxidant and in the mitochondrial Q pool serving the respiratory chain may serve important roles in energy metabolism, redox homeostasis and the level of oxidative stress.     

Pretreatment of polypropylene films for the creation of thin polymer layers,part 1: The use of chemical,electrochemical, and UV methods

The surface of a polypropylene (PP) film was activated with chemical, electrochemical, and physical methods, and the effectiveness of these methods was compared. The effects of PP activation were assessed with attenuated total reflection IR spectroscopy (ATR‐IR), SEM microscopy, and an analysis, based on the liquid contact angle, of the free energy components of the surface. The activation of the PP surface, which was dependent on the oxidizing medium, increased the energy of the PP surface layer and formed new chemical (carbonyl) groups, which were identified by IR (ATR) absorption spectroscopy and confirmed by selective surface dyeing. The treatments were ranked in the following order of increasing effectiveness: UV irradiation < 3M nitric acid < 30% hydrogen peroxide < silver nitrate (electrochemical method) < chromic mixture. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011