Agents and actions. Supplements最新文献

The aim of the present study was to investigate, whether nitric oxide (NO) modifies prostacyclin synthesis in endothelial cells. Two different NO-donors: SIN-1 (3-morpholino sydnonimine) and GEA 3175 (4-aryl-substituted oxatriazol derivative), and the NO-synthesis inhibitor; L-NAME were used. Endothelial cells were incubated with the tested compounds with or without Ca ionophore A23187 stimulation. SIN-1 (> 33 microM) and GEA 3175 (> 1 microM) increased the endothelial cGMP levels independently of A23187 stimulation. SIN-1 did not influence prostacyclin synthesis. GEA 3175 (> 33 microM) increased prostacyclin synthesis up to 2-fold, when incubated without A23187. GEA 3175 with A23187 induced about 30% inhibition in prostacyclin synthesis. L-NAME decreased unstimulated prostacyclin synthesis and this inhibition was reversed by GEA 3175. Obviously NO is able to modulate prostacyclin synthesis, however, much higher concentrations are needed than those to increase cGMP synthesis.

Mitogenic effects of TXA2 in vascular smooth muscle cells are discussed to be dependent on the age of the donor organism. The present study investigates the contribution of TXA2 on PDGF-induced proliferation of bovine coronary artery smooth muscle cells (BCA-SMC) isolated from adult animals. Radioligand binding studies revealed high affinity TXA2 binding sites (Kd = 1.6 nM) in these cells. TXA2-mimetics alone showed no proliferative effect in BCA-SMC, assessed by [3H]thymidine incorporation. However, PDGF-stimulated proliferation was potentiated two-fold receptor-dependently by TXA2-mimetics. Thus, vasoconstrictory eicosanoids released from activated platelets might aggravate proliferation of vascular smooth muscle cells at sites of vessel injury in the adult organism.

Relaxing effects of the nitric oxide donors GEA 3175 (3-aryl-substituted oxatriazole derivative), SIN-1 and sodium nitroprusside (SNP) were compared in the rat bronchial rings in vitro. In epithelium intact rings, after metacholine precontraction ED50 of GEA 3175 and SNP were similar (2 and 3.5 microM respectively) while the maximum effect of the former was bigger (92% and 54% respectively). SIN-1 was less potent (ED50 50 microMx, maximum 55%). In the absence of the epithelium the effect of GEA 3175 was attenuated, while that of SIN-1 or SNP were abolished. In the KCl precontracted rings the effects of all compounds were smaller than after metacholine precontraction. Removal of the epithelium did not alter the effects of GEA 3175 or SIN-1 but clearly increased that of SNP (change of EC50 from 10 to 0.7 microM).

Oral Defibrotide decreased leukocyte and platelet counts, raised by cholesterol diet, and the area (%) of aorta endothelial surface involved in atherosclerosis. Frequency of intimal thickening in blood vessels of kidneys and hearts and in cardiac valves was reduced by oral Defibrotide by 47%, 29% and 17%. It is suggested that oral Defibrotide reduced the involvement of the aorta in the atherosclerotic process by acting on leukocytes and platelets, to both reduce their number and deactivate them.

Rheumatoid arthritis (RA) is characterized by inflammation of synovium, in which immunoglobulin-secreting plasma cells are generally present. The forces driving immunoglobulin expression in RA synovium are unknown. Sequences of VH and VK transcripts from an RA synovial cDNA library demonstrate patterns of somatic mutation typical of an antigen-driven response. Moreover, 5% of the kappa repertoire appears to derive from the same B cell progenitor, suggesting an oligoclonal response. Immunoglobulin expression in this synovium thus appears to result from antigen stimulation. In addition, this patient's synovium is enriched for unusually long VK-JK joins (CDR3s), suggesting abnormal selection or regulation of the B cell response in RA.

A growing body of evidence demonstrates that elevated expression of the endothelial cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 at sites of inflammation in vivo is due in whole or part to the upregulation of transcription of their respective genes. Pharmacologic antagonism of transcription from these genes may therefore represent a novel approach to the development of anti-inflammatory therapeutics. This paper reviews our current understanding of nuclear factors which act to regulate the transcriptional activity of the E-selectin, VCAM-1 and ICAM-1 genes, and discusses that evidence which suggests that the nuclear transcription factor NF-kappa B acts as a dominant regulator of transcription from these genes.

The possibility of designing sequence-directed recognition peptides (complementary peptides) able to non covalently associate target peptides or proteins is one of the most important applications deriving from the Molecular Recognition Theory [MRT]. Complementary peptides can be used widely not only as synthetic ligands for the development of affinity purification strategies to isolate target peptides or proteins from crude sources, but more importantly as peptidyl antagonists to inhibit biologically relevant interactions, or to probe functional sites in proteins and corresponding receptors.

Several integrin alpha subunits have structural variants that are identical in their extracellular and transmembrane domains but that differ in their cytoplasmic domains. In the present study, we examined the possibility that the A and B variants of the alpha 6 beta 1 integrin laminin receptor differ in function. P388D1 macrophages that had been transfected with the alpha A integrin subunit were 3-4 fold more migratory than P388D1 macrophages that had been transfected with the alpha 6 B integrin subunit. Deletion of the alpha 6 cytoplasmic domain markedly inhibited the ability of the alpha 6 beta 1 receptor to promote migration.