An experimental collagen-impregnated dacron graft: Potential for endothelial seeding

This study evaluates the potential for endothelial seeding of a collagen-impregnated Dacron graft with or without surface modifiers (fibronectin, heparin) to attach and retain these cells during flow. Human umbilical endothelial cells were harvested, cultured, labeled with Indium111-oxine and seeded onto 30 mm X 4 mm diameter grafts. Six graft surfaces were studied: 1) a collagen-impregnated Dacron graft, HemashieldR (C); 2) C + fibronectin (C + F); 3) C + heparin (C + H); 4) C + F + H; 5) HytrelR + F (Hyt + F); and 6) Hyt + F + H. Radioactive loss determined the percentage attachment and then percentage retention of labeled inoculum after a one-hour in vitro perfusion. Scanning electron and light microscopy demonstrated the endothelium on the graft surface following perfusion. Fibronectin-coated grafts had a significantly higher percentage attachment than those without fibronectin (ANOVA, P less than 0.05). However, the percentage retention following perfusion was similar for all Dacron grafts and statistically inferior to the HytrelR grafts studied (ANOVA, P less than 0.05). SEM evaluation of the C + F + H graft surface was qualitatively the most impressive Dacron surface for seeding, yet was inferior to the HytrelR graft. We conclude that fibronectin benefits the initial attachment of endothelium to collagen-coated Dacron rivaling the HytrelR surface. Fibronectin does not improve percentage retention of the HemashieldR surface during perfusion, therefore, some of its initial benefit is lost.     

Limitations of current medical treatments for depression: Disturbed circadian rhythms as a possible therapeutic target

The proportion of diagnosed depressives prescribed antidepressants has increased markedly over the last 20 years, mainly following the introduction of the selective serotonin reuptake inhibitors. However, currently available antidepressants have notable limitations, relating to their only moderate efficacy relative to placebo, relatively slow onset of action, possible withdrawal symptoms, and problems of compliance. Sleep disturbances are often used to identify newly presenting depressive patients, and may be part of a more general alteration of bodily rhythms. There are links between pharmacological treatments and circadian rhythms in depression, which might represent another, new option for the development of a therapeutic approach to depression treatment. Many antidepressants affect sleep, some are sedative, and others have been used specifically in severely insomniac depressives. Disturbances in circadian rhythms may be an integral part of depressive mechanisms, and normalising them via an innovative mechanism of antidepressant action may be a fruitful avenue in the search for improved antidepressant agents.