Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus

Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y₁₂ could serve as components of dual anti-platelet therapy. We have found that a selective A_2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y₁₂ inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A_2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146.     

Dynamic anti‐windup compensator for fractional‐order system with time‐delay

This paper describes the results of introducing an additional dynamic element to an anti‐windup compensator from control quality and stability area anslysis viewpoint. The analyzed system consists of a first‐order plant with time delay and a fractional‐order PI controller, to present the discussed approach. The controller is tuned based on Hermite‐Biehler and Pontryagin theorems. In the paper, the stability analysis and tracking performance are presented based on both simulation and experimental results. The experiments have been performed using Inteco Modular Servo System with performance evaluated on the basis of the selected performance criterion, namely the Integral of Absolute Error, to verify the applicability of the proposed method. The results have proven that use of the additional dynamic element provides a wider range of controller parameters to ensure stability of the closed‐loop system and better tracking performance in comparison to the system without anti‐windup compensation or system with a standard anti‐windup compensator. It is actually the first time that this type of analysis for dynamic element compensation in anti‐windup framework has been presented for fractional‐order systems. In addition, all the obtained results are referred to the experimental data.     

The Involvement of the Endogenous Opioid System in the Gastrointestinal Aging in Mice and Humans

Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.     

Functionalized Nano Graphene Platelets as Green Catalyst to Synthesize New and Known Benzoyl-1,4-diazanaphthalene and Study of Their Local Aromaticity

Functionalized graphene has been prepared and employed for the solvent-free synthesis of some novel and known benzoyl-1,4-diazanaphthalene from the condensation of various arylglyoxals with 4-bezoyl-1,2-phenylenediamine. Catalyst loads as low as 0.003 g could be used leading to high yields of pure products. Magnetic, geometry, and electronically based indices have been also employed to investigate the correlation between aromaticity variation in new formed ring (ring A) and yield of reaction.     

Dominance and heterosexual attraction.

Four experiments examined the relation between behavioral expressions of dominance and the heterosexual attractiveness of males and females. Predictions concerning the relation between dominance and heterosexual attraction were derived from a consideration of sex role norms and from the comparative biological literature. All four experiments indicated an interaction between dominance and sex of target. Dominance behavior increased the attractiveness of males, but had no effect on the attractiveness of females. The third study indicated that the effect did not depend on the sex of the rater or on the sex of those with whom the dominant target interacted. The fourth study showed that the effect was specific to dominance as an independent variable and did not occur for related constructs (aggressive or domineering). This study also found that manipulated dominance enhanced only a male's sexual attractiveness and not his general likability. The results were discussed in terms of potential biological and cultural causal mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integrating evolutionary and social exchange perspectives on relationships: Effects of gender, self-appraisal, and involvement level on mate selection criteria.

Two studies examined which traits males and females desire in partners at various levels of relationship development in an attempt to integrate evolutionary models (which emphasize sex differences) and social exchange models (which emphasize self-appraisals). In Study 1, male and female students specified their minimum criteria on 24 traits for a date, sexual partner, exclusive dating partner, marriage partner, and 1-night sexual liaison. They also rated themselves on the same dimensions. Sex differences were greatest for casual sexual liaisons, with men's criteria being consistently lower than women's. Men's self-ratings were generally less correlated with their criteria for a 1-night stand, as well. Study 2 replicated the findings of Study 1, adding several modifications, including a measure of Ss' sex typing. Sex typing had few effects. The advantages of combining social psychological and evolutionary perspectives are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of instructions concerning ownership of a toy on preschoolers' sharing and defensive behaviors.

68 preschoolers 30–60 mo old were told that a toy belonged either to them or to the class or were given no specific instructions. Their subsequent behavior with the toy was observed. Children of all ages defended the toy more in the "yours" condition than in the "class" condition. Girls, but not boys, exhibited more defensive behavior with age. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)