Optimal Planar Flow Network Designs for Tissue Engineered Constructs with Built-in Vasculature

Convective delivery of nutrients is important to enhance mass transport within tissue engineered (TE) products. Depending on the target tissue, an ideal TE product will have an integrated microvasculature that will eliminate mass transport limitations that can occur during product growth in vitro and integration in vivo. A synthetic approach to develop microvasculature involves development of network designs with efficient mass transfer characteristics. In this paper, utilizing a planar bifurcating network as a basis, we develop an approach to design optimal flow networks that have maximum mass transport efficiency for a given pressure drop. We formulated the optimization problem for a TE skin product, incorporating two types of duct flow, rectangular and square, and solved using a generalized reduced gradient algorithm. Under the conditions of this study, we found that rectangular ducts have superior mass transport characteristics than square ducts. Microvascular area per volume values obtained in this work are significantly greater than those reported in the literature. We discuss the effect of network variables such as porosity and generations on the optimal designs. This research forms the engineering basis for the rational development of TE products with built-in microvasculature and will pave the way to design complex flow networks with optimal mass transfer characteristics.     

Disparate in vitro and in vivo antileukemic effects of resveratrol,a natural polyphenolic compound found in grapes

Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenol found in grapes and grape wine, has been reported to exhibit cardioprotective and chemopreventive activity against chemical carcinogenesis. It has also been shown to have growth inhibitory activity toward solid tumors in vivo. However, the antitumor activity of resveratrol against hematologic tumors in vivo has not been examined. In this study, the antileukemic activity of resveratrol in vitro and in vivo was examined using a mouse myeloid leukemia cell line (32Dp210). Treatment of 32Dp210 leukemia cells with resveratrol at micromolar concentrations (25-50 micromol/L) significantly and irreversibly inhibited their clonal growth in vitro. The clonal growth inhibition by resveratrol was associated with extensive cell death and an increase in hypodiploid (sub-G1) cells. Resveratol caused internucleosomal DNA fragmentation, suggesting apoptosis as the mode of cell death in 32Dp210 cells. DNA fragmentation was associated with activation of caspase-3, because cleavage of procaspase-3 was detected in resveratrol-treated cells. Although 32Dp210 cells treated with resveratrol in vitro did not produce leukemia in vivo, only a weak antileukemic effect of resveratrol was observed when administered orally. At doses of 8 mg or 40 mg/kg body daily, five times/wk, resveratrol did not affect the survival of mice injected with leukemia cells. Weak potential antileukemic activity of resveratrol was suggested only at a dose of 80 mg/kg body (2 survivors of 14 mice treated). Thus, despite strong antiproliferative and proapoptotic activities of resveratrol against 32Dp210 cells in vitro, a potential antileukemia effect in vivo, if present, occurs only in a small fraction of mice.     

Evidence for polar positional information independent of cell division and nucleoid occlusion

We present evidence that, in Escherichia coli, polar positional information is present at midcell independent of known cell division factors. In filamented cells, IcsA, which is normally polar, localizes at or near potential cell division sites. Because the cell pole is derived from the septum, the sites to which IcsA localizes in filaments correspond to future poles. IcsA localization to these sites is independent of FtsZ, MinCDE, septation, and nucleoid occlusion, indicating that positional information for the future pole is independent of cell division and chromosome positioning. Upon IcsA localization to these sites, septation is inhibited, suggesting that IcsA recognition of this polar positional information may influence cell division.     

Pediatric Advanced Life Support (PALS): the current guidelines

Every 5 years the American Heart Association (AHA) updates the Guidelines for CPR and Emergency Cardiovascular Care (ECC). The ECC Guidelines 2000 incorporates all the current consensus of experts, from not only a variety of disciplines, but also a variety of countries and cultures and is evidence based. The new Guidelines emphasize interventions to reduce the risk of sudden deaths, early identification of respiratory failure and shock and implementation of Advanced Life Support (ALS) to treat respiratory and cardiac arrest.