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Nitric oxide has been investigated widely both during neurodevelopment and in neurological diseases. However, whilst it has been established that nitric oxide-producing enzymes of nitric oxide synthase family are expressed in cerebellar Purkinje neurons, the effects of nitric oxide on the viability and morphology of these neurons remain unknown. Here, we have demonstrated that the activity of neuronal nitric oxide synthase, but not the inducible or endothelial forms of this enzyme, is required to support the survival of a proportion of cerebellar Purkinje neurons in vitro. We discovered that donation of high concentrations of exogenous nitric oxide reduces Purkinje neuron survival in culture and that peroxynitrite is also toxic to these cells. Finally, we demonstrated that exogenous nitric oxide and peroxynitrite reduce both the magnitude and the complexity of the neurite arbour extended by cerebellar Purkinje neurons. Taken together, these findings reveal that whilst a low level of endogenous nitric oxide, released by the activity of neuronal nitric oxide synthase, is beneficial to cerebellar Purkinje neurons in vitro, high levels of exogenous nitric oxide and peroxynitrite are detrimental to both the survival of these neurons and to their ability to extend processes and form functional neural networks.

A series of novel cationic detergents that contain cleavable hydrophilic isothiuronium headgroups was synthesized, and their utility in controlled assembly of plasmid DNA into small stable particles with high DNA concentration investigated. The detergents have alkyl chains of C(8)-C(12) and contain hydrophilic isothiuronium headgroups that give relatively high critical micelle concentration (CMC) to the detergents (>10 mM). The isothiuronium group masks a sulfhydryl group on the detergent and can be cleaved in a controlled manner under basic conditions to generate a reactive thiol group. The thiol group can undergo a further reaction after the detergents have accumulated on a DNA template to form a disulfide-linked lipid containing two alkyl chains. The pH-dependent kinetics of cleavage of the isothiuronium group, the CMC of the surfactants, the formation of the complexes, and the transfection efficiency of the DNA complexes have been investigated. Using the C(12) detergent, a approximately 6 kilo-basepair plasmid DNA was compacted into a small particle with an average diameter of around 40 nm with a approximately -13 mV zeta-potential at high DNA concentration (up to 0.3 mg/mL). The compounds were well tolerated in cell culture and showed no cytotoxicity under their CMCs. Under appropriate conditions, the small particle retained transfection activity.

Acute toxicity of ethylphosphate, diethylphosphate and metaphosphate of S-ethylisothiuronium does not differ significantly when the drugs are administered to albino female mice intraperitoneally, intramuscularly or subcutaneously. However, this toxicity diminishes 4--5-fold during intragastric administration. The substances are approximately 100 mg/kg more toxic for Wistar rats as compared to mice. The radioprotective doses of the compounds administered intramuscularly ten times exert no effect on the rat behaviour, weight, peripheral blood composition, weight coefficients or histological structure of the internal organs.

The acute toxicity of AESe, 2-ASe, and Se-MEG was estimated in mice after i.v., i.p. and s.c. application. In all forms of application, 2-ASe was found to have the lowest toxicity. The study of excretion showed that administered compounds are excreted practically completely within seven days, mostly by urine. The excretion by faeces is very low and by exhalation is under the threshold of demonstrability. The metabolism of 2-ASe is slow, most of it is excreted without any change; AESe is transformed into a mixture of 2-ASe and Se-MEG. Se-MEG is excreted by urine totally metabolized as trimethylselenium ion.

Radioprotective properties of Se-2-aminoethylioselenouronium bromide hydrobromide, 2-aminoselenoazoline and of selenium analogue of mercaptoethylguanidine were followed. Radio-protective effectiveness comparable with classical thiol radioprotectiva was manifested by 2-aminoselenoazoline. In the other two compounds there was on the contrary found a synergism of toxicity and radiation.