Arginine-Based Inhibitors of Nitric Oxide Synthase: Therapeutic Potential and Challenges

In the past three decades, nitric oxide has been well established as an important bioactive molecule implicated in regulation of cardiovascular, nervous, and immune systems. Therefore, it is not surprising that much effort has been made to find specific inhibitors of nitric oxide synthases (NOS), the enzymes responsible for production of nitric oxide. Among the many NOS inhibitors developed to date, inhibitors based on derivatives and analogues of arginine are of special interest, as this category includes a relatively high number of compounds with good potential for experimental as well as clinical application. Though this group of inhibitors covers early nonspecific compounds, modern drug design strategies such as biochemical screening and computer-aided drug design have provided NOS-isoform-specific inhibitors. With an emphasis on major advances in this field, a comprehensive list of inhibitors based on their structural characteristics is discussed in this paper. We provide a summary of their biochemical properties as well as their observed effects both in vitro and in vivo. Furthermore, we focus in particular on their pharmacology and use in recent clinical studies. The potential of newly designed specific NOS inhibitors developed by means of modern drug development strategies is highlighted

Mikroelektrodové pole na bázi organických elektrochemických tranzistorů pro monitorování buněčných kultur v reálném čase

A microplate with a multielectrode array of 96 organic electrochemical transistors (OECTs) based on the semiconductive polymer poly(3,4-ethylenedioxythio-phene):poly(styrene sulfonic acid) PEDOT:PSS was developed and fabricated by the screen printing method. It consists of a microplate of a 12 × 8 chimney–well array with transistors on the bottom. The OECT is circular with a channel of 1.5 mm2 in the centre surrounded by the circular gate electrode.Mikroelektrodové pole s multielektrodovým uspořádáním 96 organických elektrochemických tranzistorů (OECT) založených na polovodivém polymeru poly (3,4-ethylendioxythiophen): poly (styrensulfonová kyselina) PEDOT: PSS byla vyvinuta a vyrobena metodou sítotisku. Skládá se z destičky 12 × 8 s komínovými jamkami s tranzistory na dně. Kruhový OECT s kanálem o průměru 1,5 mm2 je uprostřed obklopen kruhovou řídící elektrodou

Conductive Polymer PEDOT:PSS-Based Platform for Embryonic Stem-Cell Differentiation

Organic semiconductors are constantly gaining interest in regenerative medicine. Their tunable physico-chemical properties, including electrical conductivity, are very promising for the control of stem-cell differentiation. However, their use for combined material-based and electrical stimulation remains largely underexplored. Therefore, we carried out a study on whether a platform based on the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) can be beneficial to the differentiation of mouse embryonic stem cells (mESCs). The platform was prepared using the layout of a standard 24-well cell-culture plate. Polyethylene naphthalate foil served as the substrate for the preparation of interdigitated gold electrodes by physical vapor deposition. The PEDOT:PSS pattern was fabricated by precise screen printing over the gold electrodes. The PEDOT:PSS platform was able to produce higher electrical current with the pulsed-direct-current (DC) electrostimulation mode (1 Hz, 200 mV/mm, 100 ms pulse duration) compared to plain gold electrodes. There was a dominant capacitive component. In proof-of-concept experiments, mESCs were able to respond to such electrostimulation by membrane depolarization and elevation of cytosolic calcium. Further, the PEDOT:PSS platform was able to upregulate cardiomyogenesis and potentially inhibit early neurogenesis per se with minor contribution of electrostimulation. Hence, the present work highlights the large potential of PEDOT:PSS in regenerative medicine