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The thermodynamic behavior of mixed monolayers of cardiolipin-dipalmitoylphosphatidylcholine (CLP-DPPC) and cardiolipin-dipalmitoylphosphatidylethanolamine (CLP-DPPE) is investigated by studying their Langmuir surface pressure and surface potential isotherms at different cardiolipin molar fractions. The overall thermodynamic behavior is independent of mole fraction for the mixed CLP-DPPC monolayers while a critical fraction exists for the CLP-DPPE monolayers.

Three phospholipase-like myotoxins, Bothrops asper myotoxin II, Agkistrodon piscivorus piscivorus K49 and Vipera ammodytes ammodytin L, can bind to long-chain fatty acids in a spontaneous autocatalytic reaction without the presence of calcium ions as cofactors. A phospholipase A2, with lysine or serine at position 49 in the active site instead of the expected aspartate residue, is found in several snake venoms. Membrane leakage is caused by these myotoxins through a unique cytolitic mechanism despite their lack of catalytic activity or calcium binding.These myotoxins are the first protein group that undergo acylation spontaneously with free fatty acids.

Rufini, S., P. De Vito, N. Balestro, M. Pescatori, P. Luly, and S. Incerpi. PLA2 stimulation of [Na.sup.+]/[H.sub.+] antiport and proliferation in rat aortic smooth muscle cells. Am. J. Physiol. 277 (Cell Physiol. 46): C814-C822, 1999.--The proliferative properties and the ability to stimulate the [Na.sup.+]/[H.sup.+] antiport activity of a secretory phospholipase [A.sub.2] were studied in rat aortic smooth muscle cells in culture: The requirement of the enzymatic activity of phospholipase [A.sub.2] to elicit mitogenesis was assessed by the use of ammodytin L, a [Ser.sub.49] phospholipase [A.sub.2] from the venom of Vipera ammodytes, devoid of hydrolytic activity. We propose that the proliferative effect is mediated by the same transduction pathway for both proteins. In particular, 1) both secretory phospholipase [A.sub.2] and ammodytin L stimulated thymidine incorporation in a dose-dependent manner; 2) both proteins affected the cell cycle, as assessed by cell growth and fluorescence-activated cell sorting experiments; 3) both phospholipase [A.sub.2] and ammodytin L increased intracellular pH, a permissive factor for cell proliferation, through activation of the [Na.sup.+]/[H.sup.+] antiport; 4) ammodytin L was able to displace the [sup.125]I-labeled phospholipase [A.sub.2] from specific binding sites in a concentration range consistent with that capable of eliciting a cellular response; and 5) the inhibition by heparin was similar for both proteins, taking into account the ratio of heparin to protein. In conclusion, the enzymatic activity of phospholipase [A.sub.2] is not required for the stimulation of mitogenesis. The inhibitory effect of heparin combined with its therapeutic potential could help to clarify the role of phospholipase [A.sub.2] in the pathogenesis of several preinflammatory situations. phospholipases [A.sub.2]; snake venom; ammodytin L; [Na.sup.+]/[H.sup.+] antiport; growth factors; heparin

Recently, a study has shown that a polymorphism in the region of MIR1279 modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the TRAF3IP2 gene have been described in association with systemic lupus erithematosus (SLE) susceptibility and with the development of pericarditis, our aim is to verify if the MIR1279 gene variability could also be involved. The rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic discrimination assay in 315 Italian SLE patients and 201 healthy controls. Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control association study and a genotype/phenotype correlation analysis were performed. We also constructed a pericarditis genetic risk profile for patients with SLE. The full sequencing of the MIR1279 gene in patients with SLE did not reveal any novel or known variation. The variant allele of the rs1463335 SNP was significantly associated with susceptibility to pericarditis (P = 0.017 and OR = 1.67). A risk profile model for pericarditis considering the risk alleles of MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients with 4 or 5 risk alleles have a higher risk of developing pericarditis (OR = 4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we describe for the first time the contribution of a MIR1279 SNP in pericarditis development in patients with SLE and a genetic risk profile model that could be useful to identify patients more susceptible to developing pericarditis in SLE. This approach could help to improve the prediction and the management of this complication. [ABSTRACT FROM AUTHOR]