The possible interrelation of ethanol and the membrane protein molecules such as TRP ion channels in the whole living organism has not been studied. In the present research we study the influence of ethanol (50%) and agonist of TRPM8 ion channel L-menthol (1% in 50% ethanol) application to abdominal skin on the thermoregulatory response to cooling in rats. We used two types of cooling with the different rates of skin temperature decrease - 0.1 °C/sec for rapid and 0.005°C/s for slow cooling. It was shown, that the effects of ethanol and activation of the cold-sensitive TRPM8 ion channel are mainly directed at different components of thermoregulatory metabolic response to cold. Menthol, as an agonist of the TRPM8 ion channel, besides the constrictor vascular response stimulates predominantly the emergency first phase of metabolic response which appears only at rapid cooling without any effect on the second phase of metabolic response to cooling. Ethanol inhibits the most powerful second phase of metabolic response to cold which is manifested at decreased deep body temperature and is associated with the development of not only non-shivering but also shivering thermogenesis. Effect of ethanol is accompanied by the acceleration of the deep body temperature fall. Ethanol does not prevent the effect of menthol on thermoregulatory blood vessel and emergency phase of metabolic response, and the activation of the cold-sensitive TRPM8 ion channel by menthol has no obvious influence on the effects of ethanol – inhibition being the most powerful thermogenic component of the metabolic response to cold. Show less

In this investigation, Rifabutin dithiocarbamate (RFND) was labeled with Technetium-99m (99mTc) using tricarbonyl technique. The labeled RFND was further characterized in terms of radiochemical purity, stability in saline & serum, in vitro bacterial binding, biodistribution in animal model rats and for scintigraphic accuracy in animal model rabbit. Finally different radiobiological characteristics of the 99mTc(CO)3-RFND was compared with the recently reported 99mTc-RFN. It was observed that the dithiocarbamate form of RFN showed better radiochemical purity, stability in saline, bacterial binding, biodistribution and targeted imaging than the recently reported 99mTc-RFN. These better radiobiological parameters posed 99mTc(CO)3-RFND as a more reliable agent for tuberculosis imaging. Show less

Canavan disease (CD) is a globally occurring but rare human spongiform leukodystrophy that is associated with inborn errors affecting the activity of aspartoacylase (ASPA), an enzyme highly expressed in oligodendrocytes that hydrolyzes N-acetylaspartate (NAA). Lack of ASPA activity is associated with the inability of oligodendrocytes to build or maintain axon-enveloping myelin sheaths. The primary source of NAA in brain is neurons, cells that synthesize but cannot catabolize it. Neurons also synthesize N-acetylaspartylglutamate (NAAG) from NAA and glutamate but cannot catabolize this substance as well. For their metabolism, these substances are released to extracellular fluid and are metabolized by oligodendrocyte ASPA and astrocyte NAAG peptidase respectively. A hypothesis developed suggested that the cause of the leukodystrophy component in CD was due to release of NAAG by neurons at white matter nodes of Ranvier, its catabolism by astrocytes forming NAA and increased osmotic-hydrostatic pressure as a result of its buildup at these nodes due to the lack of ASPA activity. In this communication, we provide evidence supporting this hypothesis and comment on the cause and possible cure for human CD. Show less