Modulation of TXA2 generation of platelets by human lipoproteins

The lipoprotein (LP) fractions VLDL, LDL, HDL2 and HDL3 were prepared by ultracentrifugation of plasma from healthy volunteers and from patients with coronary heart disease (CHD). We investigated the capacity of platelets from healthy volunteers and patients with atherosclerosis to generate thromboxane A2 (TXA2) during spontaneous clotting of whole blood under the influence of the lipoprotein fractions. In our experiments the serum concentration of TXB2, reflecting the capacity of platelets to generate TXA2 during clotting, depends on several factors: the type of LP fraction used, the blood used for generation of TXA2, and for the same LP fraction whether it was taken from plasma of healthy volunteers or patients with CHD. VLDL prepared from plasma of healthy volunteers inhibited but VLDL prepared from plasma of patients with CHD enhanced the TXA2 formation of platelets from healthy volunteers (p less than 0.05, resp.). LDL from CHD patients inhibited the TXA2 formation of platelets from atherosclerotic patients (p less than 0.01). The HDL subfractions HDL2 and HDL3 from healthy volunteers inhibited TXA2 formation by platelets from healthy volunteers as well as those from atherosclerotic patients (p less than 0.05; p less than 0.01, respectively). HDL2 from patients with CHD inhibited only the TXA2 formation of platelets from healthy volunteers (p less than 0.01), whereas HDL3 from CHD patients inhibited only the TXA2 formation of platelets from atherosclerotic patients (p less than 0.01).     

Blood Lipids Profiling of Preterm Neonates in the First Day of Life for Identification of Early Biomarkers of Sepsis and Pneumonia

Russian Journal of Bioorganic Chemistry - The early period of postnatal development of premature infants is often complicated by bacterial infections, in particular respiratory infections, which in...     

Involvement of GDNF and LIMK1 and heat shock proteins in drosophila learning and memory formation

Molecular mechanisms of the synapse and dendrite integrity maintenance and their disruption in psychiatric and neurodegenerative diseases (NDD) are being studied intensively to identify target genes for therapeutic activities. It is suggested that synapse is a tripartite system in which glia, alongside with well-studied pre- and postsynaptic neurons, represents a third, poorly studied partner in synaptic transmission involved in a positive feedback loop between the other two partners. It is the glia cell-derived neurotrophic factor (GDNF) and the transmembrane proteins, neuregulins, that mediate bidirectional coupling between presynaptic neurons and their postsynaptic targets. Neuregulins are structurally related to the epidermal growth factor and have a cytoplasmic domain that interacts with intracellular LIM kinase 1 (LIMK1), the key enzyme of actin remodeling. Since neurons and axons that do not receive a sufficient GDNF supply are at risk of degeneration and synapse elimination, GDNF became a central target factor in human NDD therapy. The delivery of GDNF-producing stem cells to the nidus of neurodegeneration by transplantation surgery is an efficient tool for NDD treatment. A new approach is proposed based on the use of the Drosophila heat shock (hs) promoter that responds to the mammalian body temperature and ensures constant expression of the human GDNF gene. The Drosophila models facilitate studying the role of each component of the bidirectional signaling between pre- and postsynaptic neurons in the development of the key diagnostic NDD symptom—a defective memory formation resulted from synaptic atrophy. To assess the efficiency of memory formation depending on the level of GDNF and LIMK1 brain expression, we used the Drosophila strains simulating different nervous system disorders: GDNF, the transgenic flies that carry the human GDNF gene under hs-promoter, l(1)ts403, the mutants with disruption of heat shock proteins (HSPs) mRNA nuclear trafficking, and agn ^ts3 carrying a mutation in LIMK1 gene. We investigated at the behavioral (learning/memory) level the functional connections between GDNF, LIMK1 and HSP signaling transductions that might offer promising targets for complex approaches to NDD treatment.