Comparative antimicrobial activity of lysosubtilin and its acid-resistant derivative,Fermosorb

Comparative data are given on the in vitro activity of lysosubtilin against micro-organisms and its acid-resistant derivative, Fermosorb. The lytic activity Fermosorb against all micro-organisms tested was higher (in the range of 0.9-7.7 and 4.1-13.5% for bacteria and filamentous fungi/yeasts, respectively) than that achieved by the action of lytic enzymes present in lysosubtilin solution. All six lysosubtilin-resistant strains tested were Fermosorb-susceptible. Considering the increase in the incidence of antibiotic resistance antimicrobial enzymotherapy or enzymoprophylaxis by means of Fermosorb might be considered for the treatment of intestinal infections in animals.     

BODIPY derivatives with near infra-red absorption as small molecule donors for bulk heterojunction solar cells

The study of small donor molecules as the active component of organic solar cells continues to attract considerable attention due to the range of advantages these molecules have over their polymeric counterparts. Here we report the synthesis and solar cell fabrication of three BODIPY small molecule donors. Two of the dyes feature triphenylamine and phenothiazine as donor units attached to the meso and α-positions of the BODIPY core (TPA-PTZ-DBP and PTZ-TPA-BDP). Additionally, we have synthesised a push–pull derivative featuring phenothiazine moieties in the α-positions and a nitrobenzene in the meso-position (N-TPA-BDP) in order to investigate what effect this type of functionalisation has on the photovoltaic properties compared to the other dyes. The optoelectronic properties were investigated and the dyes showed broad absorption in the near-infrared with high extinction coefficients. Electrochemical measurements indicated good reversibility for the dyes redox processes. In contrast with the all-donor functionalised systems, N-TPA-BDP demonstrated extensive HOMO–LUMO overlap by DFT. The dyes were investigated as donor molecules in bulk heterojunction solar cells along with PC₇₁BM, and under optimal donor to acceptor ratio PTZ-TPA-BDP showed the highest PCE of 1.62%. N-PTZ-BDP:PC₇₁BM was the only blend to further improve upon thermal annealing reaching the highest conversion efficiency among the dyes of 1.71%. A morphology comprised of finely mixed donor and acceptor components is observed for BHJ blends of each of the three donors at their optimum fullerene content. Upon thermal annealing, these morphological features remain mostly the same for PTZ-TPA-BDP:PC₇₁BM and TPA-PTZ-DBP:PC₇₁BM blends whereas for N-PTZ-BDP:PC₇₁BM the domains show a larger size. These dyes show that phenothiazine functionalisation of BODIPY is useful for solar cells because it gives strong and broad absorption extending to the near infra-red and materials with reversible redox properties – both of which are desirable for organic solar cells.

We report the synthesis of donor/acceptor functionalised BODIPY derivatives and their incorporation as donor molecules in bulk heterojunction solar cells.     

Isolation and characterization of human anterior cruciate ligament-derived vascular stem cells

The anterior cruciate ligament (ACL) usually fails to heal after rupture mainly due to the inability of the cells within the ACL tissue to establish an adequate healing process, making graft reconstruction surgery a necessity. However, some reports have shown that there is a healing potential of ACL with primary suture repair. Although some reports showed the existence of mesenchymal stem cell-like cells in human ACL tissues, their origin still remains unclear. Recently, blood vessels have been reported to represent a rich supply of stem/progenitor cells with a characteristic expression of CD34 and CD146. In this study, we attempted to validate the hypothesis that CD34- and CD146-expressing vascular cells exist in hACL tissues, have a potential for multi-lineage differentiation, and are recruited to the rupture site to participate in the intrinsic healing of injured ACL. Immunohistochemistry and flow cytometry analysis of hACL tissues demonstrated that it contains significantly more CD34 and CD146-positive cells in the ACL ruptured site compared with the noninjured midsubstance. CD34+CD45- cells isolated from ACL ruptured site showed higher expansionary potentials than CD146+CD45- and CD34-CD146-CD45- cells, and displayed higher differentiation potentials into osteogenic, adipogenic, and angiogenic lineages than the other cell populations. Immunohistochemistry of fetal and adult hACL tissues demonstrated a higher number of CD34 and CD146-positive cells in the ACL septum region compared with the midsubstance. In conclusion, our findings suggest that the ACL septum region contains a population of vascular-derived stem cells that may contribute to ligament regeneration and repair at the site of rupture.     

Effect of bone morphogenetic protein-2-expressing muscle-derived cells on healing of critical-sized bone defects in mice.

BACKGROUND: Cells that express bone morphogenetic protein-2 (BMP-2) can now be prepared by transduction with adenovirus containing BMP-2 cDNA. Skeletal muscle tissue contains cells that differentiate into osteoblasts on stimulation with BMP-2. The objectives of this study were to prepare BMP-2-expressing muscle-derived cells by transduction of these cells with an adenovirus containing BMP-2 cDNA and to determine whether the BMP-2-expressing muscle-derived cells would elicit the healing of critical-sized bone defects in mice. METHODS: Primary cultures of muscle-derived cells from a normal male mouse were transduced with adenovirus encoding the recombinant human BMP-2 gene (adBMP-2). These cells (5 yen 10(5)) were implanted into a 5-mm-diameter critical-sized skull defect in female SCID (severe combined immunodeficiency strain) mice with use of a collagen sponge as a scaffold. Healing in the treatment and control groups was examined grossly and histologically at two and four weeks. Implanted cells were identified in vivo with use of the Y-chromosome-specific fluorescent in situ hybridization (FISH) technique, and their differentiation into osteogenic cells was demonstrated by osteocalcin immunohistochemistry. RESULTS: Skull defects treated with muscle cells that had been genetically engineered to express BMP-2 had >85% closure within two weeks and 95% to 100% closure within four weeks. Control groups in which the defect was not treated (group 1), treated with collagen only (group 2), or treated with collagen and muscle cells without adBMP-2 (group 3) showed at most 30% to 40% closure of the defect by four weeks, and the majority of the skull defects in those groups showed no healing. Analysis of injected cells in group 4, with the Y-chromosome-specific FISH technique showed that the majority of the transplanted cells were located on the surfaces of the newly formed bone, but a small fraction (approximately 5%) was identified within the osteocyte lacunae of the new bone. Implanted cells found in the new bone stained immunohistochemically for osteocalcin, indicating that they had differentiated in vivo into osteogenic cells. CONCLUSIONS: This study demonstrates that cells derived from muscle tissue that have been genetically engineered to express BMP-2 elicit the healing of critical-sized skull defects in mice. The cells derived from muscle tissue appear to enhance bone-healing by differentiating into osteoblasts in vivo. Clinical Relevance: Ex vivo gene therapy with muscle-derived cells that have been genetically engineered to express BMP-2 may be used to treat nonhealing bone defects. In addition, muscle-derived cells appear to include stem cells, which are easily obtained with muscle biopsy and could be used in gene therapy to deliver BMP-2.     

Toxicological Potential of Cadmium Impact on Rainbow Trout (Oncorhynchus mykiss) in Early Development

Bulletin of Environmental Contamination and Toxicology - Cadmium (Cd) is a toxic element widely distributed in the aquatic environment and producing a wide variety of harmful effects. In this...     

Costs and financial feasibility of malaria elimination

The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework-potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed.     

PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets

The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result of the emerging drug resistance to anti-VEGF therapies. PDGF-CC is the third member of the PDGF family discovered after more than two decades of studies on PDGF-AA and PDGF-BB. The biological function of PDGF-CC and the underlying cellular and molecular mechanisms remain largely unexplored. Here, using different animal models, we report that PDGF-CC inhibition by neutralizing antibody, shRNA, or genetic deletion suppressed both choroidal and retinal neovascularization. Importantly, we revealed that PDGF-CC targeting acted not only on multiple cell types important for pathological angiogenesis, such as vascular mural and endothelial cells, macrophages, choroidal fibroblasts and retinal pigment epithelial cells, but also on the expression of other important angiogenic genes, such as PDGF-BB and PDGF receptors. At a molecular level, we found that PDGF-CC regulated glycogen synthase kinase (GSK)–3β phosphorylation and expression both in vitro and in vivo. Activation of GSK3β impaired PDGF-CC–induced angiogenesis, and inhibition of GSK3β abolished the antiangiogenic effect of PDGF-CC blockade. Thus, we identified PDGF-CC as an important candidate target gene for antiangiogenic therapy, and PDGF-CC inhibition may be of therapeutic value in treating neovascular diseases.     

Linear lesions provide protection from atrial fibrillation induction with rapid atrial pacing

INTRODUCTION: In the animal model, segmentation of the atria with radiofrequency-generated linear lesions (LL) using the loop catheter has been shown to be highly effective in terminating chronic atrial fibrillation (AF). This study addresses the question whether the same lesion set also would prevent reinduction and sustainability of AF. METHODS AND RESULTS: We studied two groups of dogs. The AF group included eight dogs in which the atria were paced until chronic AF was present. After 6 months of sustained AF, the dogs were converted to normal sinus rhythm (NSR) by the creation of LL in both atria. Rapid atrial pacing was restarted 6 months later and continued for 4 weeks. In the NSR group, there were nine dogs in NSR without inducible AF at baseline. LL were created, and after 6 months rapid atrial pacing was applied for 4 weeks. Rhythm status was monitored weekly. Transthoracic echocardiography was performed at baseline, before linear lesion placement, and before pacing/repacing. At the conclusion of the study, the hearts were excised and examined. The lesions were stained, and their quality was assessed. AF was induced in a much shorter interval in the dogs in which AF had previously been present than in NSR dogs (8 +/- 5 days vs 25 +/- 13 days; P < 0.05). LL prevented sustainability of AF induced via rapid pacing once the pacing stimulus was stopped. Incomplete lesions were associated with increased inducibility of atrial tachycardia and AF. CONCLUSION: In this animal model of AF, LL are not only capable of terminating chronic AF, but also lead to self-termination of AF once the rapid pacing is stopped. Self-termination of AF after induction with rapid pacing was not observed in this AF model in the absence of LL. In the dogs with 6 months of AF, the presence of AF led to increased atrial susceptibility to AF induction by rapid pacing, even with LL and after 6 months of recovery. Incomplete LL allows induction of atrial tachycardia and AF.