Heparan sulphate inhibition of cell proliferation induced by TGFβ and PDGF

The effect of glycosaminoglycans (GAGs) on the proliferation of smooth muscle cells (SMC) and fibroblasts was assessed by culturing cells with or without GAGs. Porcine heparan sulphate (HS) inhibited proliferation in a dose dependent manner. At 167 μg/ml of HS this reached 88% and 72% inhibition of SMC and fibroblast growth, respectively. Pig and beef mucosal heparins also blocked proliferation, but to a lesser extent. In contrast, beef lung heparin, chondroitin sulphate, and dermatan sulphate failed to block growth factor induced proliferation. Continuous presence of HS was not required, suggesting that the inhibitory effects resulted from a direct effect on the cell rather than an interaction of the GAG with growth factors. The mechanism by which GAGs inhibit proliferation will be addressed in future studies

Recovery of Streptococcus mutans and Streptococcus sanguis from a dental explorer after clinical examination of single human teeth

Certain aspects of the bacterial flora adhering to a dental explorer following a tactile diagnostic examination of a single tooth were investigated. Plaque present on the explorer was dislodged, and suspended into a reduced transport fluid by sonification. After serial dilution, suitable aliquots were placed on a high sucrose-containing medium, and on a mannitol medium. Colonies resembling Streptococcus mutans and Streptococcus sanguis were enumerated on these media. The explorer removed approximately 3-7 x 106 bacteria from a single tooth. Streptococcus mutans accounted for 17 per cent of the isolates from carious teeth and for 1.6 per cent of the isolates found on noncarious teeth. This difference was significant at the p Strep. sanguis were significantly higher in material removed from noncarious teeth than in plaque removed from the carious teeth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33912/1/0000177.pd

Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis

Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH

Update on the safety and bioequivalence of biosimilars – focus on enoxaparin

Walter Jeske,1 Jeanine M Walenga,1 Debra Hoppensteadt,2 Jawed Fareed2 1Cardiovascular Institute; 2Department of Pathology, Loyola University Chicago, Maywood, IL, USA Abstract: Generic forms of chemically-derived drugs must exhibit chemical identity and be bioequivalent in healthy human subjects. The use of generic drugs results in a considerable savings of healthcare expenditures. Biologic drugs are produced in living systems or are derived from biologic material and extend beyond proteins to include antibodies, polysaccharides, polynucleotides, and live viral material. Such drugs pose a challenge to characterize as they tend to be larger in size than chemically-derived drugs, can exhibit a variety of post-translational modifications, and can have activities that are dependent on specific conformations. Biosimilars are not true generics, but rather, exhibit a high degree of similarity to the reference product and are considered to be biologically and clinically comparable to the innovator product. Therefore, the development process for biosimilars is more complex than for a true generic. Guidance is now available from the US Food and Drug Administration and from the European Medicines Agency for the development of biosimilar drugs. Biosimilar drugs are expected to have a major impact in the management of various diseases in coming years. Keywords: generic, biosimilar, low molecular weight hepari