Effect of vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles

The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS-PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system.     

Catoessa boscii (Crustacea, Isopoda, Cymothoidae) parasitic on Carangoides malabaricus (Pisces, Carangidae) from India. Taxonomy and host-parasite relationships

Catoessa boscii (Bleeker, 1857) (Crustacea, Isopoda, Cymothoidae), is redescribed according to the type specimen observed by Schioedte and Meinert (1884) extant in the Rijksmuseum von Natuurlijke Historie, Leiden (RMNH) and from many additional specimens recently collected in India from Carangoides malabaricus (Pisces, Carangidae). This study allows an updating of the diagnosis of the genus Catoessa and of the species Catoessa boscii. Some parasite-host relationships were studied during the year. Prevalence and sex ratio of parasites varied according to the month, and the sex and size of hosts.     

Precipitation of nanohydroxyapatite on PLLA/PBLG/Collagen nanofibrous structures for the differentiation of adipose derived stem cells to osteogenic lineage

Tissue engineering and nanotechnology have enabled engineering of nanostructured materials to meet the current challenges in bone treatment owing to rising occurrence of bone diseases, accidental damages and defects. Poly(l-lactic acid)/Poly-benzyl-l-glutamate/Collagen (PLLA/PBLG/Col) scaffolds were fabricated by electrospinning and nanohydroxyapatite (n-HA) was deposited by calcium-phosphate dipping method for bone tissue engineering (BTE). The abundance and accessibility of adipose derived stem cells (ADSC) may prove to be novel cell therapeutics for bone repair and regeneration. ADSCs were cultured on these scaffolds and were induced to undergo osteogenic differentiation in the presence of PBLG/n-HA for BTE. The cell-biomaterial interactions were analyzed using cell proliferation, SEM and CMFDA dye extraction techniques. Osteogenic differentiation of ADSC was confirmed using alkaline phosphatase activity (ALP), mineralization (ARS) and dual immunofluorescent staining using both ADSC marker protein and Osteocalcin, which is a bone specific protein. The utmost significance of this study is the bioactive PBLG/n-HA biomolecule introduced on the polymeric nanofibers to regulate and improve specific biological functions like adhesion, proliferation and differentiation of ADSC into osteogenic lineage. This was evident from the immunostaining and CMFDA images of ADSCs showing cuboidal morphology, characteristic of osteogenic lineage. The observed results proved that the PLLA/PBLG/Col/n-HA scaffolds promoted greater osteogenic differentiation of ADSC as evident from the enzyme activity and mineralization profiles for bone tissue engineering.     

In vivo tumor imaging using polo-box domain of polo-like kinase 1 targeted peptide

Polo-like kinase 1 (Plk1) is a regulator of cell cycle progression during mitosis; it is overexpressed in many different tumors and has been implicated as a potential antimitotic target. Plks are characterized by the presence of a highly conserved C-terminal polo-box domain (PBD) that is involved in regulating kinase activity. The phosphopeptide Pro-Leu-His-Ser-p-Thr (PLHSpT) is a potent selective inhibitor of the PBD of human plk1 that acts by inducing mitotic arrest and apoptotic cell death in cancer cells. We synthesized cRGDyK-S-S-CPLHSpT to exploit the drug delivery and molecular imaging using positron emission tomography (PET). The peptide was blocked dramatically proliferation of tumor in?vitro and in?vivo. It was attempted to develop and show a tumor PET image with the radiolabeled-peptide. Here we showed the peptide is promising not only as an anticancer drug, but also as a radioligand for tumor diagnosis with PET. We expect that our contribution will provide new insights into the design of Plk1 peptide inhibitors and have significant implications for anticancer therapy and tumor diagnosis.     

Blockade of the receptor for advanced glycation end products attenuates acetaminophen-induced hepatotoxicity in mice

BACKGROUND AND AIM: Severe injury to the liver, such as that induced by toxic doses of acetaminophen, triggers a cascade of events leading to hepatocyte death. It is hypothesized that activation of the receptor for advanced glycation end products (RAGE) might contribute to acetaminophen-induced liver toxicity by virtue of its ability to generate reactive oxygen species, at least in part via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and thereby activate downstream signaling pathways leading to cellular injury. METHODS: A model was employed in which toxic doses of acetaminophen (1125 mg/kg) were administered to C57BL/6 mice. To block RAGE, mice received murine soluble (s) RAGE, the extracellular ligand binding domain of the receptor that acts as a decoy to interrupt ligand-RAGE signaling. RESULTS: Animals treated with sRAGE displayed increased survival compared with vehicle treatment, and markedly decreased hepatic necrosis. Consistent with an important role for RAGE-triggered oxidant stress in acetaminophen-induced injury, a significant reduction of nitrotyrosine protein adducts was observed in hepatic tissue in sRAGE-treated versus vehicle-treated mice receiving acetaminophen, in parallel with significantly increased levels of glutathione. In addition, pro-regenerative cytokines tumor necrosis factor-alpha and interleukin-6 were increased in sRAGE-treated versus vehicle-treated mice. CONCLUSION: These findings implicate RAGE-dependent mechanisms in acetaminophen-induced liver damage and suggest that blockade of this pathway may impart beneficial effects in toxin-induced liver injury.     

QSAR analysis of caffeoyl naphthalene sulfonamide derivatives as HIV-1 integrase inhibitors

Human immunodeficiency virus type 1 (HIV-1) integrase is a potential target for anti-HIV therapy. It is an essential enzyme required for replication of the acquired immunodeficiency syndrome (AIDS) virus. Caffeoyl naphthalene sulfonamide derivatives act against HIV integrase and thus have the potential to become a part of an anti-HIV drug regimen. Although caffeoyl naphthalene sulfonamide derivatives have all the features required of good anti-HIV agents such as the presence of bis-catechol moieties, polyaromatic rings, and a central linker, they do not perform well as anti-HIV agents in cell-based assays, that is, they do not stop viral replication at nontoxic concentration. We carried out a quantitative structure–activity relationship (QSAR) study of caffeoyl naphthalene sulfonamide derivatives via the software WIN CAChe 6.1 and STATISTICA to improve its activity. QSAR reveals that if partition coefficient, connectivity index, and shape index of these molecules are altered, the activity is likely to increase. On the basis of the QSAR model, we designed a new series of compounds, calculated the activities, and found that they were more potent than the existing compounds.