Computational analysis of the effect of the type of LVAD flow on coronary perfusion and ventricular afterload

We developed a computational model to investigate the hemodynamic effects of a pulsatile left ventricular assist device (LVAD) on the cardiovascular system. The model consisted of 16 compartments for the cardiovascular system, including coronary circulation and LVAD, and autonomic nervous system control. A failed heart was modeled by decreasing the end-systolic elastance of the ventricle and blocking the mechanism controlling heart contractility. We assessed the physiological effect of the LVAD on the cardiovascular system for three types of LVAD flow: co-pulsation, counter-pulsation, and continuous flow modes. The results indicated that the pulsatile LVAD with counter-pulsation mode gave the most physiological coronary blood perfusion. In addition, the counter-pulsation mode resulted in a lower peak pressure of the left ventricle than the other modes, aiding cardiac recovery by reducing the ventricular afterload. In conclusion, these results indicate that, from the perspective of cardiovascular physiology, a pulsatile LVAD with counter-pulsation operation is a plausible alternative to the existing LVAD with continuous flow mode. An erratum to this article can be found at     

Experimental study on the effects of chronic iodine excess on thyroid function, structure, and autoimmunity in autoimmune-prone NOD.H-2h4 mice

Iodine is an essential component of thyroid hormones; high intake may lead to thyroid disease. Epidemiologic researches have shown that exposure to iodine may be involved in the onset and development of autoimmune thyroiditis. Iodine may induce hypothyroidism in patients with autoimmune thyroiditis in a dose-dependent manner. The aim of the present study was to investigate the effects of dosages of iodine on thyroid autoimmunity, morphology, structure, and function in autoimmune-prone animals. NOD.H-2h4 mice were randomly divided into normal iodine, 5-fold, 10-fold, 100-fold, 1,000-fold iodine excess group, anesthetized by diethyl ether and bleed from eye socket vein at 4, 8, 16, and 24 weeks after the commencement of experiment. Iodine and thyroid hormone levels in the thyroid tissue and sera, serum thyroglobulin antibody levels, as well as thyroid gland histological appearance were measured. Excessive iodine caused thyroid goiter, and there was a positive correlation between the thyroid weight and the dosage of iodine (r = 0.64–0.92, P < 0.01). Iodine overdose ultrastructurally damaged thyroid epithelial cells in a dose-dependent manner. The incidence of thyroiditis, as well as the degree of lymphocytic infiltration in the thyroid gradually increased as the dosage increased (r = 0.87–0.98, P ≤ 0.05). Excessive iodine intake might induce goiter, lead to thyroiditis, worsen lymphocytic infiltration, as well as damage to the thyroid follicular structure in a dose-dependent manner in autoimmune-prone NOD.H-2h4 mice.     

Reversal of P‐glycoprotein‐mediated multi‐drug resistance by the E3 ubiquitin ligase Cbl‐b in human gastric adenocarcinoma cells

P‐glycoprotein (P‐gp)‐mediated multi‐drug resistance (MDR) is a major barrier to the effective chemotherapy of many cancers. Recent studies have shown that inhibition of the PI3K/Akt signalling pathway can reverse P‐gp‐mediated MDR. We investigated the expression of activated Akt (p‐Akt) in 124 human gastric carcinoma tissue samples. Ubiquitous p‐Akt expression was recorded in the majority (88/124). There was a significant correlation between p‐Akt expression and the expression of P‐gp. In the adriamycin‐resistant MDR gastric carcinoma cell line SGC7901/ADR, p‐Akt expression was increased in comparison with the parental cell line SGC7901. Treatment of SGC7901/ADR cells with the PI3K inhibitor LY294002 reduced the expression of both p‐Akt and P‐gp. To explore the role of ubiquitin ligase Cbl‐b in this regulatory pathway, SGC7901/ADR cells were transfected with a plasmid overexpressing wild‐type Cbl‐b. This down‐regulated the expression of both p‐Akt and P‐gp. Furthermore, resistance to chemotherapeutic drugs was partially reversed. These results demonstrate an important role for Cbl‐b in reversing P‐gp‐mediated gastric cancer MDR through suppression of the PI3K/Akt signalling pathway and the down‐regulation of P‐gp expression. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.