Background-Possible intermediate circulating markers linking blood stasis to vein remodeling were explored in patients with varicose veins in the lower limbs. Methods and Results-Blood was sampled at rest (supine position) and after a stasis of 30 minutes both in the varicose vein (limbs hanging down) and in the brachial vein (arm hanging down) as a paired control. Several endothelial and leukocyte markers were measured in plasma with the use of ELISA kits. Angiotensin-converting enzyme activity was determined by use of a specific substrate. Matrix metalloproteinases (MMPs) 9 and 2 were evaluated with the use of gelatin zymography. No markers were significantly modified after 30 minutes of blood stasis in the brachial vein. After 30 minutes of blood stasis in the varicose vein, oxygen partial pressure decreased (PϽ0.01). Although thrombomodulin, von Willebrand factor, vascular endothelial growth factor, and MMP-2 were not modified in these conditions, the proteins released by proteolysis from the endothelial membrane intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and angiotensin-converting enzyme were increased (PϽ0.01). After blood stasis in varicose veins, the leukocyte markers lactoferrin, myeloperoxidase, and interleukin-8 were not modified, whereas L-selectin shed from leukocytes increased (PϽ0.05), and a major increase in pro-MMP-9, which is released from tertiary granules during polymorphonuclear activation, was observed (Pϭ0.0001).
Conclusions-The
Summaryle) The pineal fraction F 3 increased the hypothalamic FSH-and LH-RF content in vitro and in vivo. This may be a consequence of a decrease in the secretion of the hypothalamic releasing factors in presence of the F 3 pineal factor. 2e) Serotonin modifies the hypothalamic gonadotropic RF content inhibiting the secretion and synthesis of the releasing factors. 3e) As with serotonin, microinjections of melatonin into the lateral ventricle performed at the same time as subcutaneous injections of nialamide are followed by a significant decrease of hypothalamic RF content.
SummaryThe fraction F8 obtained after gelfiltration of a pineal extract on Sephadex G-25 (Fine) which inhibits in vitro the secretion of FSH of the anterior hypophysis has been chromatographed on the weak cation-exchanger Amberlite IRC-50~ XE-64. This method which was very useful as a purification step of the Sephadex G-25 fraction F2 and has been used with success to isolate the peptide hormones of the neurohypophysis, does appear to be unsuitable for further purification of a pineal fraction with inhibiting activity.Under the experimental conditions used little or no of the original inhibiting activity of the F3 fraction was observed and sometimes even a rather strong stimulating activity was found after the separation on Amberlite IRC-50, XE-64.
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