Reduction In Levels Of Markers Research Articles

Regulation of global protein translation and protein degradation in aerobic dormancy

We hypothesized that protein turnover would be substantially suppressed during estivation in the land snail, Otala lactea, as part of a wholesale move to conserve ATP in the hypometabolic state, and that decreased rates of protein synthesis and degradation would be mediated by altering the phosphorylation state of key proteins. Rates of protein translation, measured in vitro, decreased by approximately 80% in extracts of foot muscle and hepatopancreas after 2 days of estivation, and this reduction was associated with strong increases in the phosphorylation of ribosomal factors, eIF2 alpha and eEF2, as well as decreased phosphorylation of 4E-BP1. Reductions in levels of markers of ribosomal biogenesis and a tissue-specific reduction in the phosphorylation state of eIF4E and eIF4GI were also evident after 14 days of estivation. Activity of the 20S proteasome decreased by 60-80% after 2 days of estivation and this decrease was mediated by protein kinase G in vitro, whereas protein phosphatase 2A activated the proteasome. Levels of protein carbonyls did not change in snail tissues during estivation whereas the expression heat shock proteins increased, suggesting that protein resistance to damage is enhanced in estivation. In conclusion, protein synthesis and degradation rates were coordinately suppressed during estivation in O. lactea and this is associated with the phosphorylation of ribosomal initiation and elongation factors and the 20S proteasome.

ACE INHIBITORS ARE RATIONAL PHARMACOTHERAPY OF ENDOTHELIAL DYSFUNCTION

Aim. To study effects of ACE inhibitor perindopril on markers of endothelial dysfunction in therapy of patients with arterial hypertension (HT). Material and methods. 82 patients with HT, complicated by ischemic stroke were involved in the study. 30 patients with uncomplicated HT were included into control group. Antihypertensive therapy with perindopril (52 patients) or amlodipine (30 patients) was conducted additionally to standard neurotropic therapy in hypertensive patients with ischemic stroke. Phase-contrast microscopy and enzyme immunoassay were used for screening of endothelial dysfunction markers (blebbing, desquamated endothelial cells, membrane-liberated parts, sPECAM-1). Results. Reduction in levels of markers of endothelial dysfunction was observed among patients treated with perindopril in comparison with patients who did not receive ACE inhibitor or patients of control group. Target levels of blood pressure were reached in 96% of patients treated with perindopril. Сonclusion. ACE inhibitors in therapy patients with HT reduce endothelial dysfunction additionally to antihypertensive effect.

Significance of serum carcinoembryonic antigen and CA 15-3 in monitoring advanced breast cancer patients treated with systemic therapy: a large-scale retrospective study.

The significance of serum carcinoembryonic antigen (CEA) and CA 15-3 in monitoring advanced breast cancer is still controversial. To clarify this issue, the Tumor Marker Study Group of the Japanese Breast Cancer Society conducted a large-scaled retrospective study. The findings from four clinical trials and seven institutes of 528 patients with advanced breast cancer were collected. Three-hundred forty-eight patients, in whom both serum CEA and CA 15-3 were measured during therapy, were selected for analysis. The pretreatment positivity rate of CA 15-3 was significantly higher than that of CEA (p<0.0001). Time-to-progression (TTP) in CEA- and CA 15-3-positive patients was significantly shorter than TTP in negative patients. The changes in either marker level correlated well with response to therapy in marker-positive patients but not in negative patients. TTP in the marker-positive patients with a greater than 20%-reduction in either marker level during therapy was significantly longer than that in positive patients without such a reduction (p<0.01 for CEA and CA 15-3). CA 15-3 is more useful for monitoring advanced breast cancer than CEA and a greater than 20%-reduction in marker levels suggests longer TTP in pretreatment marker-positive patients.