The expression of lysyl-oxidase gene family members in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are malignant disorders originating from clonal expansion of a single neoplastic stem cell and characteristically show an increase in bone marrow reticulin fibers. Lysyl oxidases (LOXs) are copper-dependent amine oxidases that play a critical role in the biogenesis of connective tissue by crosslinking extracellular matrix proteins, collagen and elastin. Expression of LOX gene family members is increased in disorders associated with increased fibrosis. To evaluate involvement of LOX gene family in various MPNs. In-situ hybridization was used to detect Lysyl-Oxidase family members in bone marrow biopsies from patients with different MPNs. We compared normal bone marrows and those from patients with polycythemia vera, essential thrombocythemia, chronic myeloid leukemia, and primary myelofibrosis (PMF). Serum levels of lysyl-oxidase from patients with PMF and healthy controls were also examined. LOX gene family was not detected in normal bone marrows. All members of the LOX gene family were over expressed in PMF. In other MPNs a differential pattern of expression was observed. Differences in gene expression were statistically significant (P < 0.010). The medianserum LOX levels in normal controls was 28.4 ± 2.5 ng\ml and 44.6 ± 9.44 ng\ml in PMF (P = 0.02). The varying pattern of expression of LOX genes may reflect differences in the pathophysiology of bone marrow fibrosis in these MPNs. These observations could be used as the basis for future targeted therapy directed against bone marrow fibrosis.

Solid lipid nanoparticles and nanoemulsions with solid shell: Physical and thermal stability.

HYPOTHESIS: Nanoemulsions (NE) and solid lipid nanoparticles (SLN) used for drug delivery should have a solid shell to be stable during long shelf life and become liquid at human body temperature. The core components of lipid nanoparticles can be partially incorporated into the shell and affect the physical and thermal stability. EXPERIMENTS: We prepared NE and SLN by the phase inversion temperature (PIT) method. Solidification of the surfactants Tween60 and Span 60 on the surface of NE droplets with paraffin oil resulted in the formation of the solid shell. SLN contained stearic acid in the core and the same surfactants in the solid shell. The size, structure and stability of the NE and SLN were studied by DLS and cryo-TEM. Their crystallization and melting were analyzed using DSC. FINDINGS: The lipid nanoparticles were resistant to aggregation and sedimentation and hold up to at least two cycles of heating to 50-60 °C and subsequent cooling to 5 °C, even though the upper temperatures were higher than the melting point of the surfactant shell. The expected liquid core/solid shell morphology of NE was confirmed. SLN were composed of a semi-liquid core of supercooled stearic acid melt and coated with a solid surfactant shell, so they can be treated as NE. Stearic acid molecules penetrated the shell, leading to an increase in its melting point.

[Co-adaptation of enzymatic systems of cells and blood supply in smooth muscle tumors of the corpus uteri].

We investigated co-adaptation of enzymatic systems of cells using data on activity of NAD(Ph)-dependent enzymes and AgNOR proteins of vascular endothelium vis-a-vis angiogenesis in benign and malignant smooth muscle tumors of the corpus uteri. Overall metabolic activity (NAD-H2 diaphorase) was found to directly correlate with angiogenesis and endothelial vessel proliferation (r = 0.76 and 0.84, respectively). SDH-regulated oxidation in the main metabolic succession of a tricarbonic acid cycle depended on blood supply and endothelial vessel proliferation (r = 0.84 and 0.92, respectively; p = 0.04). A similar relationship was shown for anaerobic glycolysis of SDH (LDH content), on the one hand, and blood supply and endothelial vessel proliferation(r = 0.57 and 0.70, respectively; p = 0.02), on the other. Hence, metabolic profile varied in unaltered myometrium and tumor with variable cellular density and peculiar extracellular matrix. The highest levels of metabolic activity with NAD(Ph)-dependent enzyme co-adaptation was observed in sarcomas which were also characterized by the highest vascular density for endothelial proliferation.