Role of Protein Kinase Akt Activation in Protective Effect of Ganglioside GM1 on PC12 Cells Exposed to H2O2.

Micro- and nanomolar concentrations of ganglioside GM1 improved viability of neuronal PC12 cells under conditions of oxidative stress and reduced H2O2-induced ROS accumulation in these cells. These effects were more pronounced at micromolar concentrations. GM1 in concentrations of 100 nM and 10 µM significantly and substantially increased basal activity of protein kinase B (Akt) (the level of phosphorylated Akt form), but had virtually no effect on its expression in PC12 cells. In the presence of PI3K inhibitor LY294002 preventing protein kinase Akt activation, the protective effect of GM1 significantly decreased. These findings suggest that activation of protein kinase Akt by GM1 contributes to improvement of PC12 cell viability by this ganglioside.

Monocyte chemoattractant proteins in the pathogenesis of systemic sclerosis.

Activation of the immune system and increased synthesis of extracellular matrix proteins by fibroblasts are hallmarks in the pathogenesis of SSc. The molecular mechanisms underlying the infiltration of inflammatory cells into the skin and the subsequent activation of fibroblasts are still largely unknown. Chemokines are a family of small molecules that are classified according to the position of the NH(2)-terminal cysteine motif. Recent data indicate that chemokines and in particular two members of the subfamily of monocyte chemoattractant proteins, MCP-1 (CCL-2) and MCP-3 (CCL-7), might be involved in the pathogenesis of SSc. MCP-1 and -3 are overexpressed by SSc fibroblasts and in skin lesions from SSc patients compared to healthy controls. MCP-1 and -3 are chemotactic for inflammatory cells and stimulate their migration into the skin. In addition to their pro-inflammatory effects, MCP-1 and -3 contribute to tissue fibrosis by activating the synthesis of extracellular matrix proteins in SSc fibroblasts. Therapeutic strategies targeting MCP-1 have revealed promising results in several animal models of SSc. Antagonists against the receptor CCR2 are currently tested in clinical trials of a variety of diseases and also represent interesting candidates for target-directed therapy in SSc.

EULAR Scleroderma Trials and Research group statement and recommendations on endothelial precursor cells.

Systemic sclerosis (SSc) is characterised by a progressive microangiopathy that contributes significantly to the morbidity of patients with SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers of endothelial precursor cells (EPCs) might also contribute to the vascular pathogenesis of SSc. However, different protocols for isolation, enrichment, culture and quantification of EPCs are currently used, which complicate comparison and interpretation of the results from different studies. The aim of the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) group expert panel was to provide recommendations for standardisation of future research on EPCs. Consensus statements and recommendations were developed in a face to face meeting by an expert panel of the basic science working group of EUSTAR. The findings were: cardiovascular risk factors and medications such as statins should be described in detail. A detailed description of methods considering isolation, culture, enrichment and detection of EPCs should be given. For in vitro culture of EPCs, no protocol has been shown to be superior to another, but coating with laminin and type IV collagen would resemble most closely the situation in vivo. The endothelial phenotype should be confirmed in all in vitro cultures at the end of the culture period. We recommend using CD133, vascular endothelial growth factor type 2 receptor (VEGFR2) and CD34 in combination with a viability marker for quantification of EPCs in the blood. Finally, exact standard operating procedures for fluorescence-activated cell sorting (FACS) analysis are given that should be strictly followed. In summary, the EUSTAR recommendations will help to unify EPC research and allow better comparison between the results of different studies.

Effect of enkephalins on the function of calcium-regulating endocrine glands.

Experiments on rats have shown that administration of a synthetic analog of leucine enkephalin at a dose of 100 mg/kg did not change the content of the immunoreactive parathyroid hormone in the blood plasma, but eliminated the parathyroidin-stimulating effect on the cAMP concentration in the renal tissue and AP activity in the blood. We conclude that enkephalins do not influence the secretion and metabolism of the parathyroid hormone, but block its peripheral effects and stimulate thyroid C-cell function.

[Effect of enkephalins on the energy potential of the rat liver and cerebral cortex during an early period of traumatic shock]. / Vliianie énkefalinov na énergeticheskii potentsial pecheni i kory golovnogo mozga u krys v rannem periode travmaticheskogo shoka.

The experiments were performed on 86 white male rats, weighing 180-220 g. The animals with traumatic shock revealed a decrease in ATP concentration and a rise in ADP and AMP levels in the brain cortex and hepatic tissue, resulting in the energy charge reduction. The injection of synthetic leu-enkephalin analog D-ala2-arg6-leu-enkephalin to animals with traumatic shock led to energy charge normalization in the brain cortex and increase in hepatic tissue. The mechanisms of enkephalin effect on the energy metabolism during shock are discussed.

[Effect of enkephalins on the calcium-regulating function of the endocrine glands]. / Vliianie enkefalinov na funktsiiu kal'tsiireguliruiushchikh endokrinnykh zhelez.

Experiments on rats have shown that administration of a synthetic analog of leuenkephalin at a dose of 100 mg/kg did not change the content of the immunoreactive parathyroid hormone in the blood plasma but removed the parathyroidin stimulating effect on the cAMP concentration in the renal tissue and AP activity in the blood. It is concluded that enkephalins do not influence the secretion and metabolism of the parathyroid hormone but block its peripheral effects and stimulate thyroid C-cell function.