Epithelial interactions and local engraftment of lung-resident mesenchymal stem cells

Multipotent mesenchymal progenitor cells, termed "mesenchymal stem cells" (MSCs), have been demonstrated to reside in human adult lungs. However, there is little information regarding the associations of these local mesenchymal progenitors with other resident somatic cells and their potential for therapeutic use. Here we provide in vivo and in vitro evidence for the ability of human adult lung-resident MSCs (LR-MSCs) to interact with the local epithelial cells. The in vivo retention and localization of human LR-MSCs in an alveolar microenvironment was investigated by placing PKH-26 or DsRed lentivirus-labeled human LR-MSCs in the lungs of immunodeficient (SCID) mice. At 3 weeks after intratracheal administration, 19.3 ± 3.21% of LR-MSCs were recovered, compared with 3.47 ± 0.51% of control fibroblasts, as determined by flow cytometry. LR-MSCs were found to persist in murine lungs for up to 6 months and demonstrated preferential localization to the corners of the alveoli in close proximity to type II alveolar epithelial cells, the progenitor cells of the alveolar epithelium. In vitro, LR-MSCs established gap junction communications with lung alveolar and bronchial epithelial cells and demonstrated an ability to secrete keratinocyte growth factor, an important modulator of epithelial cell proliferation and differentiation. Gap junction communications were also demonstrable between LR-MSCs and resident murine cells in vivo. This study demonstrates, for the first time, an ability of tissue-specific MSCs to engraft in their organ of origin and establishes a pathway of bidirectional interaction between these mesenchymal progenitors and adult somatic epithelial cells in the lung.     

Distraction osteogenesis and nonunion of the docking site: is there an ideal treatment option?

Docking sites are the result of a classic bone transport technique for dealing with bone loss. Union may prove to be the rate-limiting step in the duration of treatment. Strategies to improve union have focused on surgical manipulation such as immediate coaptation of the margins of the segmental defect in the process of acute shortening to prevent fibrocartilaginous capping of the ends of bone during transport. This procedure has the highest success rate for union but is limited by its effect on the limb's vascularity. Other techniques for improving union involve compression, alternate compression-distraction, and bone grafts, all of which induce union to a variable degree. The application of external stimulators and bone morphogenetic proteins, the use of which is supported in fracture healing and even regenerate formation, is as yet unproven at docking sites.     

Utility of repeat genotypic resistance testing and clinical response in patients with three class resistance and virologic treatment failure

We sought to determine the utility of repeat genotypic resistance testing (GRT) and the clinical response in HIV-1-infected patients with known resistance to three of the major classes of antiretroviral drugs. The HIV-1 genetic sequences for 20 patients who had high-level 3 class resistance demonstrated on a prior GRT (3C-GRT 1) measured during the period from November 1, 2000 through July 1, 2004 were retrospectively evaluated. At the time of 3C-GRT 1, the median CD4 count and HIV-1 RNA viral load were 168 cells/mm(3) and 4.5 log copies per milliliter, respectively. The median time to the second GRT (3C-GRT 2) was 17 months. At that time, the median CD4 count and VL were 140 cells/mm(3) and 4.9 log copies per milliliter (p = 0.8 and p = 0.12, respectively). On 3C-GRT 2, all patients retained essentially identical mutations, with the exception of the loss of the M184V mutation in 6 patients. After 3C-GRT 2, all patients continued on protease inhibitor-containing highly active antiretroviral therapy (HAART) regimens. At 24 weeks after 3C-GRT 2, there was no significant change in CD4 count or HIV-1 RNA viral load (p = 0.68 and p = 0.30, respectively). Repeat GRT in patients with documented high-level 3 class resistance does not provide new or clinically useful information. Under continued antiretroviral selective pressure, the viral genetic sequences in this patient population remained stable. In addition, continuing HAART regimens containing protease inhibitors appeared to forestall further immunological and virologic deterioration in patients with multiple resistance mutations. Providers should focus on obtaining access to combinations of novel agents for patients with 3 class resistance rather than repeated GRT.     

Just one cross appears capable of dramatically altering the population biology of a eukaryotic pathogen like Toxoplasma gondii

Toxoplasma gondii, an obligate intracellular protozoan of the phylum Apicomplexa, is estimated to infect over a billion people worldwide as well as a great many other mammalian and avian hosts. Despite this ubiquity, the vast majority of human infections in Europe and North America are thought to be due to only three genotypes. Using a genome-wide analysis of single-nucleotide polymorphisms, we have constructed a genealogy for these three lines. The data indicate that types I and III are second- and first-generation offspring, respectively, of a cross between a type II strain and one of two ancestral strains. An extant T. gondii strain (P89) appears to be the modern descendant of the non-type II parent of type III, making the full genealogy of the type III clonotype known. The simplicity of this family tree demonstrates that even a single cross can lead to the emergence and dominance of a new clonal genotype that completely alters the population biology of a sexual pathogen.     

An Influence of Oxygen Flow Rate and Spray Distance on the Porosity of HVOF Coating and Its Effects on Corrosion—A Review

Thermal spray coating, exceptionally high-velocity oxyfuel (HVOF), improves the corrosion resistance and wear of metal. Coating parameters play a vital role in the properties of the coating. The quality of coating can be increased by selecting appropriate coating parameters. In the case of HVOF, the oxygen flow rate and spray distance are the most significant parameters that directly influence the porosity and corrosion resistance of the coating. Porosity is essential in thermal barrier coatings for low thermal conductivity, but there is a limit of porosity beyond which it can cause failure. Hence, understanding the effects of these parameters is essential to evaluate and further minimize the porosity in order to improve the corrosion resistance and durability of the thermal barrier coating. This article reviews hot corrosion in thermal barrier coatings, the stages of corrosion, the importance of spray parameters, and the effect of the oxygen flow rate and spray distance on the corrosion resistance of HVOF-sprayed coatings. Afterwards, the coating materials, the substrate, the flow rate of oxygen, the spray distance, and the fuel used during the HVOF spraying process from recent articles are summarized. In summary, this review compares the flow rate of oxygen and the spray distance with the corrosion capacity of the coating under different corrosive environments and materials to optimize these parameters for high-quality coating, which would sustain under high temperatures for future applications.     

Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia coli

Here, the synthesis of linear polyglycerols bearing multiple copies of mono and dimannosides (LPG₄₀Man_0.60 and LPG₄₀(Manα1,2Man)_0.60) is demonstrated. A method based on label-free microscale thermophoresis is optimized to determine the direct binding affinity of multivalent mannosides for Escherichia coli (E. coli) strain ORN178 that produces the fimbriae protein FimH. It is observed that the LPG₄₀(Manα1,2Man)_0.60 exhibits only a modest onefold improvement in binding as compared to LPG₄₀Man_0.60. Nevertheless, both the multivalent mannosides display remarkably very low nm binding constant (K_d) in contrast to the high µm K_d of the single α-d -methylmannoside for intact E. coli ORN178 particles. Furthermore, in an adhesion-inhibition assay, both multivalent mannosides show 50% inhibition of bacteria adhesion to the HT-29 colon cells at low µm concentrations.     

Ectopic right coronary artery arising from the left sinus of Valsalva: A rare variant

An ectopic coronary artery is observed in 0.05–0.1% of angiographic series, may be of tangential origin or proximal endocardial pathway, may result in a slit hole that interferes with flow, and is associated with sudden death.