Acetyl-l-carnitine normalizes the impaired long-term potentiation and spine density in a rat model of global ischemia

Aim: The aim of this study was to enhance the knowledge regarding actors and intentions in the development process of a mobile phone platform for self-management of hypertension. Methods: Our research approach was a 14-month longitudinal “real-time ethnography” method of description and analysis. Data were collected through focus groups with patients and providers, patient interviews, and design meetings with researchers and experts. The analysis was informed by the concepts of actors and inscriptions in actor-network theory (ANT). Results: Our study showed that laypersons, scientific actors, as well as technology itself, might influence development processes of support for self-management of hypertension. The intentions were inscribed into the technology design as well as the models of learning and treatment. Conclusions: The study highlighted important aspects of how actors and intentions feature in the development of the mobile phone platform to support self-management of hypertension. The study indicated the multifacetedness of the participating actors, including the prominent role of technology. The concrete results of such processes included questions in the self-report system, learning and treatment models

Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

Myostatin, a TGF-beta superfamily member, is a negative regulator of muscle growth. Here we describe how myostatin activity is regulated by syndecan-4, a ubiquitous transmembrane heparan sulfate proteoglycan. During muscle regeneration the levels of both syndecan-4 and promyostatin decline gradually after a sharp increase, concurrently with the release of mature myostatin. Promyostatin and syndecan-4 co-immunoprecipitate, and the interaction is heparinase-sensitive. ShRNA-mediated silencing of syndecan-4 reduces C2C12 myoblast proliferation via blocking the progression from G1- to S-phase of the cell cycle, which is accompanied by elevated levels of myostatin and p21(Waf1/Cip1), and decreases in cyclin E and cyclin D1 expression. Our results suggest that syndecan-4 functions as a reservoir for promyostatin regulating the local bioavailability of mature myostatin. This article is protected by copyright. All rights reserved

Cytotoxicity and the effect on the inflammation response of thyme oil and thymol: evaluation in human macrophage cells

The essential oil of Thymus vulgaris L. (Lamiaceae), thyme oil, shows a great variability of its composition with six main chemotypes recognized up to now: geraniol, linalool, g-terpineol, carvacrol, thymol, and trans-thujan-4-ol/terpinen-4-ol types. Due to this large chemical diversity, the subject of several investigations was to identify and determine their properties, including their potential effect on inflammation. In our previous microbiological study, this essential oil showed a significant antibacterial activity against bacteria of the respiratory tract [1].                The present research focuses on the evaluation of its cytotoxic and antiinflammatory effect in the case of the U937 human monocyte/macrophage cell line. Thyme oil composition was determined by GC/MS. Bürker chamber was used for cell counting and flow-cytometry to evaluate cellular toxicity (using 7-AAD). Then a qPCR method was used to determine the expression of TNFα mRNA.                The main component of the tested sample of thyme oil was thymol (38.7%) that showed a concentration-dependent cytotoxicity. Non-toxic dilutions showed preventive antiinflammatory potential

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues

Background: The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. Materials and methods: In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. Results: The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. Discussion: The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening. © 2017 Knapp et al