No abstract

Previous experiments suggest that actin disassembly, perhaps at a specific site, is required for platelet secretion. Platelet stimulation by phorbol 12-myristate 13-acetate (PMA) induced pleckstrin phosphorylation, platelet aggregation, and secretion. Inhibition of protein kinase C (PKC) is accompanied by inhibition of pleckstrin phosphorylation and serotonin secretion. Here, we demonstrate the presence of myristoylated alanine-rich C kinase substrate (MARCKS), another PKC substrate, in platelets and its phosphorylation during PMA stimulation. MARCKS is known to bind actin and to cross-link actin filaments; the latter is inhibited by PKC-induced MARCKS phosphorylation. MARCKS phosphorylation and serotonin release from permeabilized platelets have the same time course and were blocked by a peptide (MPSD) with the amino acid sequence corresponding to the phosphorylation site domain of MARCKS. Pleckstrin and myosin light chain phosphorylation was not modified. A peptide (Ala-MPSD) in which the four serine residues of MPSD were substituted by alanines was ineffective. These results provide the first evidence that MARCKS may play a role in platelet secretion. Moreover, pleckstrin phosphorylation has a different time course than that of MARCKS or serotonin release and was not modified when MARCKS phosphorylation and serotonin release were inhibited, suggesting that pleckstrin is either not directly involved in secretion or that it might only be involved upstream in the cascade of events leading to exocytosis.

The LTA is potentially a valuable diagnostic tool for DHS; however, its sensitivity, specificity, NPV, and PPV seem to vary according to the drug involved in the reaction.

Scinderin is a Ca(2) also showed the presence of a Ca 2ϩ -dependent actin-binding protein that was immunologically different from gelsolin. The isolation and characterization of this protein was carried out simultaneously by two independent laboratories (4 -6). These publications showed that chromaffin cells contain a Ca 2ϩ -dependent actin-severing protein that was distinct from gelsolin, although gelsolin was also present in these cells (2, 5). The names "scinderin" (4, 5) and "adseverin" (6) were given to this protein. Cloning of scinderin cDNA and sequence analysis (7,8) demonstrated that, similarly to gelsolin, scinderin has six domains with two actin-binding sites in domains 1 and 2 (7, 9, 10). Two Ca 2ϩ

While the pathophysiology of chronic disorders varies there are three basic mechanisms-inflammation, oxidative stress and endothelial dysfunction-that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid-AAL), omega-3 (anti-inflammatory capsules-AIC) and extract with Alaskan blueberry (anti-oxidant liquid-AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels. Chronic diseases are the leading causes of death in developed countries, with atherosclerosis and its complications at the top of the list. The commonest chronic diseases-cardiovascular disease, diabetes, obesity and Alzheimer's Disease-cannot be prevented by disease or cured by medication, are more common in older patients