Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species.

Hypertension and coronary artery disease are intimately connected. The migration of circulating monocytes into the subendothelial occurs through the expression of some adhesion molecules on endothelial cells. The nuclear factor (NF)-kappaB, a redox-sensitive element, plays a key role in adhesion molecule gene induction. In this study we have compared the effects of two different angiotensin converting enzyme (ACE) inhibitors, one possessing an active sulfhydryl group (zofenopril) and one lacking this group (enalapril) on the cellular redox state (monitored by measuring intracellular reactive oxygen species and thiol status), expression of adhesion molecules, and activation of NF-kappaB in human umbilical vein endothelial cells (HUVECs). Zofenoprilat, the active form of zofenopril, significantly and dose dependently reduced the intracellular reactive oxygen species (ROS) and superoxide formation induced by oxidized low-density lipoprotein (ox-LDL) (P <.001) and tumor necrosis factor-alpha (TNF-alpha) (P <.001). Enalaprilat, the active form of enalapril, was ineffective. Zofenoprilat but not enalaprilat also decreased the consumption of the intracellular GSH induced by ox-LDL (P <.01) and TNF-alpha (P <.01). Although zofenoprilat significantly and dose dependently reduced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and E-selectin induced by ox-LDL (P <.01) and TNF-alpha (P <.01) on HUVECs, enalaprilat did not. Ox-LDL and TNF-alpha increased the activation of NF-kappaB and the preincubation of HUVECs with zofenoprilat, but not with enalaprilat, dose dependently reduced its activation (P <.001). The conclusion is that the sulfhydryl (SH)-containing ACE inhibitors may be useful in inhibiting foam cell formation and thus slow the development of atherosclerosis.

[Criteria for management and use of instrumental techniques]. / Criteri di gestione ed impiego delle tecniche strumentali.

The measurement of various parameters--be it plain temperature readings or determination of pesticides, drug monitoring or measurement of contaminants in air or water--must be carried out precisely and accurately. After purchase of the instrument, the installation qualification and the operation qualification, both produced by experts in the manufacturing company, are used to ensure correct use of the instrument. The standard operating procedures for instrument management must be sufficiently detailed to allow the operator to use the instrument correctly and, above all, must contain all the information necessary for accurate and precise calibrations. From 2002, the Food and Drug Administration will no longer accept submission of paper dossiers, so that pharmaceutical companies wishing to register a product in the USA will be obliged to submit the dossier electronically. This will involve the validation of all the software used in the management and operation of all instruments. It can be assumed that the EMEA will shortly follow the FDA, so that the validation of instrument software systems will become the rule and create new responsibilities for operators and inspectors.