Bone inductive proteins to enhance postorthodontic stability: A pilot study

Objectives:To evaluate the use of bone morphogenetic proteins to enhance postorthodontic stability in sheep and to develop a biological method of postorthodontic retention.Materials and Methods:First incisors were extracted in four mature and healthy sheep, and the second incisors were tipped reciprocally toward the midline and then retained. Dried bone matrix was injected into the distal periodontal space of the left second incisor. The right second incisor was left as a control. Both incisors were retained in the tipped position for 4 weeks. Then, the orthodontic appliance was removed and the teeth were left without retention. Six weeks later, the animals were killed and serial sections were prepared for histologic observation.Results:Unlike the control, the experimental second incisor maintained its tipped position with minimal relapse. On the distal periodontal space of the experimental tooth, areas of focal fusion between newly formed bone and newly formed areas of hypercementosis were observed. In the distal periodontal space of the control tooth, osteoclastic activity was observed along most of the socket wall, and the periodontal space appeared narrow and compressed. This brought the tooth close to the boundary of the alveolar bone, confirming the relapse observed on that side.Conclusion:This study proposes a new method of retention in which a biologically safe osteoinductive material is used to retain the teeth via induction of points of approximation between the cementum and alveolar bone.     

Full-length extracellular region of the var2CSA variant of PfEMP1 is required for specific,high-affinity binding to CSA

Pregnancy-associated malaria (PAM) is a serious consequence of sequestration of Plasmodium falciparum-parasitized erythrocytes (PE) in the placenta through adhesion to chondroitin sulfate A (CSA) present on placental proteoglycans. Recent work implicates var2CSA, a member of the PfEMP1 family, as the mediator of placental sequestration and as a key target for PAM vaccine development. Var2CSA is a 350 kDa transmembrane protein, whose extracellular region includes six Duffy-binding-like (DBL) domains. Due to its size and high cysteine content, the full-length var2CSA extracellular region has not hitherto been expressed in heterologous systems, thus limiting investigations to individual recombinant domains. Here we report for the first time the expression of the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) from the 3D7 parasite strain using the human embryonic kidney 293 cell line. We show that the recombinant extracellular var2CSA region is correctly folded and that, unlike the individual DBL domains, it binds with high affinity and specificity to CSA (K_D = 61 nM) and efficiently inhibits PE from binding to CSA. Structural characterization by analytical ultracentrifugation and small-angle x-ray scattering reveals a compact organization of the full-length protein, most likely governed by specific interdomain interactions, rather than an extended structure. Collectively, these data suggest that a high-affinity, CSA-specific binding site is formed by the higher-order structure of the var2CSA extracellular region. These results have important consequences for the development of an effective vaccine and therapeutic inhibitors.     

Composite microparticles with in vivo reduction of the burst release effect

The aim of this study was to develop microparticles containing nanoparticles (composite microparticles) for prolonged drug delivery with reduced burst effect in vitro and in vivo. Such composite microparticles were prepared with hydrophobic and biodegradable polymers [poly(ε-caprolactone), poly(lactic-co-glycolic) acid]. Ibuprofen was chosen as the model drug, and microparticles were prepared by the extraction technique with ethyl acetate as the solvent. Nanoparticles and microparticles and an ibuprofen solution (Pedea^®) were administered subcutaneously at the dose of 1 mg of ibuprofen per kg to overnight-fasted rats (male Wistar). Composite microparticles showed prolonged ibuprofen release and less burst effect when compared to simple microparticles (without nanoparticles inside) or nanoparticles both in vitro (PBS buffer) and in vivo. Moreover, ibuprofen was still detected in the plasma after 96 h with composite microparticles. Consequently, it has been demonstrated that composite microparticles were able to reduce burst release and prolong the release of ibuprofen for a long period of time.     

Accumulation and Depuration of Trace Metals in Southern Toads, Bufo terrestris, Exposed to Coal Combustion Waste

Accumulation and depuration of metals by an organism are underrepresented in the literature. We collected southern toads (Bufo terrestris) from coal by-product (ash)-contaminated and uncontaminated sites to examine metal concentrations over time. Toads were placed in four exposure regimes, then sacrificed periodically over a 5-month period, and whole-body metal levels were measured. Toads exposed to ash accumulated significant concentrations of metals. Metal concentrations changed throughout the experiment, and profiles of accumulation and depuration differed depending on the metal and exposure regime. Ash-exposed toads exhibited elevated levels of 11 of 18 metals measured. Increases ranged from 47.5% for Pb to more than 5000% for As. Eight of 18 metals did not change in control toads, while 10 of 18 metals decreased in toads removed from ash, ranging from −25% for Co to −96% for Tl. Seven metals that decreased in toads removed from ash did not change in control toads.