Ultrasound Evaluation of Chronic Venous Insufficiency.

ABSTRACT: Chronic venous insufficiency is a common condition caused by valvular incompetence and/or obstruction of the lower extremity venous system. Chronic venous insufficiency presents in a wide range of clinical presentations, ranging from mild pain or edema to the development of varicose veins and nonhealing venous ulcers. Doppler ultrasound is the preferred imaging modality in the assessment of this condition and provides both anatomical and functional information in a noninvasive, cost-effective, and radiation-free manner. Knowledge of the anatomy and nomenclature, pathophysiology, equipment requisites, scanning protocols, relevant findings, and reporting nuances is essential to the creation of an accurate and clinically actionable report. Evaluation of the superficial and deep venous system for degree and extent of reflux is necessary to establish the diagnosis and to institute appropriate treatment.

Carbon monoxide (CO) is a novel inhibitor of connexin hemichannels.

Hemichannels (HCs) are hexamers of connexins that can form gap-junction channels at points of cell contacts or "free HCs" at non-contacting regions. HCs are involved in paracrine and autocrine cell signaling, and under pathological conditions may induce and/or accelerate cell death. Therefore, studies of HC regulation are of great significance. Nitric oxide affects the activity of Cx43 and Cx46 HCs, whereas carbon monoxide (CO), another gaseous transmitter, modulates the activity of several ion channels, but its effect on HCs has not been explored. We studied the effect of CO donors (CORMs) on Cx46 HCs expressed in Xenopus laevis oocytes using two-electrode voltage clamp and on Cx43 and Cx46 expressed in HeLa cells using a dye-uptake technique. CORM-2 inhibited Cx46 HC currents in a concentration-dependent manner. The C-terminal domain and intracellular Cys were not necessary for the inhibition. The effect of CORM-2 was not prevented by guanylyl-cyclase, protein kinase G, or thioredoxin inhibitors, and was not due to endocytosis of HCs. However, the effect of CORM-2 was reversed by reducing agents that act extracellularly. Additionally, CO inhibited dye uptake of HeLa cells expressing Cx43 or Cx46, and MCF-7 cells, which endogenously express Cx43 and Cx46. Because CORM-2 carbonylates Cx46 in vitro and induces conformational changes, a direct effect of that CO on Cx46 is possible. The inhibition of HCs could help to understand some of the biological actions of CO in physiological and pathological conditions.