Diabetes mellitus type 1 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidlines

Organisation of mitochondria in living sensory neurons

AbstractIn this work, we have examined the mitochondrial organisation in living cultured primary dorsal root ganglion (DRG) neurons. Confocal microscopy and the mitochondrial potential-sensitive fluorescent dye 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolo carbocyanine iodide (JC-1) were used to visualise intracellular structures with a high and low membrane potential. Three-dimensional reconstruction revealed a mitochondrial organisation featuring separate highly polarised mitochondria, clusters of mitochondria located mainly at the base of neurite hillocks and filamentous mitochondrial structures. Filamentous mitochondria were distributed along the cell body, especially between neurites. A functional integration between mitochondrial structures is proposed

Cofilin and DNase I affect the conformation of the small domain of actin.

Cofilin binding induces an allosteric conformational change in subdomain 2 of actin, reducing the distance between probes attached to Gln-41 (subdomain 2) and Cys-374 (subdomain 1) from 34.4 to 31.4 A (pH 6.8) as demonstrated by fluorescence energy transfer spectroscopy. This effect was slightly less pronounced at pH 8.0. In contrast, binding of DNase I increased this distance (35.5 A), a change that was not pH-sensitive. Although DNase I-induced changes in the distance along the small domain of actin were modest, a significantly larger change (38.2 A) was observed when the ternary complex of cofilin-actin-DNase I was formed. Saturation binding of cofilin prevents pyrene fluorescence enhancement normally associated with actin polymerization. Changes in the emission and excitation spectra of pyrene-F actin in the presence of cofilin indicate that subdomain 1 (near Cys-374) assumes a G-like conformation. Thus, the enhancement of pyrene fluorescence does not correspond to the extent of actin polymerization in the presence of cofilin. The structural changes in G and F actin induced by these actin-binding proteins may be important for understanding the mechanism regulating the G-actin pool in cells

Gingerols: a novel class of vanilloid receptor (VR1) agonists

1. Gingerols, the pungent constituents of ginger, were synthesized and assessed as agonists of the capsaicin-activated VR1 (vanilloid) receptor. 2. [6]-Gingerol and [8]-gingerol evoked capsaicin-like intracellular Ca(2+) transients and ion currents in cultured DRG neurones. These effects of gingerols were blocked by capsazepine, the VR1 receptor antagonist. 3. The potency of gingerols increased with increasing size of the side chain and with the overall hydrophobicity in the series. 4. We conclude that gingerols represent a novel class of naturally occurring VR1 receptor agonists that may contribute to the medicinal properties of ginger, which have been known for centuries. The gingerol structure may be used as a template for the development of drugs acting as moderately potent activators of the VR1 receptor