Potent inhibition of membrane-bound rat intestinal alkaline phosphatase by a new series of phosphate analogues.

The inhibition by phosphonates and phosphate analogues of the alkaline phosphatase activity of rat intestinal brush-border membrane vesicles was studied at pH 7.5 and 30 degrees C. Phenylene-1,3-diphosphonate, 2,6-dinitrophenylphosphonate and phosphonoacetaldehyde were found to be competitive inhibitors, with Ki values in the range 16-80 microM. Adenosine 5'-[beta-thio]diphosphate and adenosine 5'[gamma-thio]triphosphate are also very potent inhibitors, with Ki values of approx. 10 microM. The inhibition produced by these thiophosphates was mainly competitive but with a slight non-competitive element. Adenosine 5'-[beta gamma-imido]triphosphate is also a competitive inhibitor of the alkaline phosphatase, but oxidation of the ribose moiety of this compound with NaIO4 results in an active-site-directed irreversible inhibitor that could be of general use in studies of the mechanism of action of this enzyme.     

Finite element simulation of an artificial intervertebral disk using fiber reinforced laminated composite model

Degeneration of intervertebral disk (IVD) has been increased in recent years. The lumbar herniation can be cured using conservative and surgical procedures. Surgery is considered after failure of conservative treatment. Partial discectomy, fusion, and total disk replacement (TDR) are also common surgical treatments for degenerative disk disease. However, due to limitations and disadvantages of the current treatments, many studies have been carried out to approach the best design of mimicking natural disk. Recently, a new method of TDRs has been introduced using nature deformation of IVD by reinforced fibers of annulus fibrosis. Nonetheless, owing to limitations of experimental works on the human body, numerical studies of IVD may help to understand load transfer and biomechanical properties within the disks with reinforced fibers. In this study, a three-dimensional (3D) finite element model of the L2-L3 disk vertebrae unit with 12 vertical fibers embedded into annulus fibrosis was constructed. The IVD was subjected to compressive force, bending moment, and axial torsion. The most important parameters of disk failures were compared to that of experimental data. The results showed that the addition of reinforced fibers into the disk invokes a significant decrease of stress in the nucleus and annulus. The findings of this study may have implications not only for developing IVDs with reinforced fibers but also for the application of fiber reinforced IVD in orthopedics surgeries as a suitable implant.     

Longevity of Toxocara cati Larvae and Pathology in Tissues of Experimentally Infected Chickens

This study was conducted to determine the distribution patterns and duration of stay of Toxocara cati larvae in organs of chickens and to investigate chronic phase and potential zoonotic risk of toxocariasis in chickens. Chickens were orally infected with 1,000 embryonated T. cati eggs and necropsied 240 days post-infection. Organs of the chickens were examined at gross and microscopic levels; tissues were digested to recover larvae. Peribronchiolitis with infiltration of lymphocytes, and hyperplasia of bronchiolar associated lymphatic tissues (BALT) and goblet cells, were evident in the lungs of infected chickens. There were mild hemorrhages and infiltration of lymphocytes and a few eosinophils in the meninges. Larvae were recovered from 30% of the exposed chickens. Larvae recovery indicated that T. cati larvae stay alive for at least 240 days in the chicken brain. Therefore, chickens may potentially act as a paratenic host in nature and transfer T. cati larvae to other hosts.     

Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid

In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations. PPI G5-Alkyl 30% indicated a decreased drug release may be due to alkyl chains on the surface of PPI, which serve as an additional hindrance for drug diffusion. In vitro cytotoxicity experiments demonstrated that co-delivery system induced apoptosis of tumor cells more efficiently than each of delivery system alone. Furthermore, these results revealed that our combined delivery platform of pTRAIL and DOX using Alkyl-modified PPI G5 can significantly improve the anti-tumor activity and this strategy might develop a new therapeutic window for cancer treatment.