A Brief History…

By Bradley J. Fikes

(Crossposted at my newspaper’s sci-tech blog).

A cheaper way to make antisense oligonucleotides From the abstract in PLoS ONE:

“Antisense oligonucleotides targeting microRNAs or their mRNA targets prove to be powerful tools for molecular biology research and may eventually emerge as new therapeutic agents. Synthetic oligonucleotides are often contaminated with highly homologous failure sequences. Synthesis of a certain oligonucleotide is difficult to scale up because it requires expensive equipment, hazardous chemicals and a tedious purification process. Here we report a novel thermocyclic reaction, polymerase-endonuclease amplification reaction (PEAR), for the amplification of oligonucleotides.”

My take: This should be of interest to companies working with RNA-based therapeutics, like Carlsbad’s Isis Pharmaceuticals or Regulus Therapeutics.

Evolution of Primary Hemostasis in Early Vertebrates From the PLoS One abstract:

Hemostasis is a defense mechanism which protects the organism in the event of injury to stop bleeding. Recently, we established that all the known major mammalian hemostatic factors are conserved in early vertebrates. However, since their highly vascularized gills experience high blood pressure and are exposed to the environment, even very small injuries could be fatal to fish. Since trypsins are forerunners for coagulation proteases and are expressed by many extrapancreatic cells such as endothelial cells and epithelial cells, we hypothesized that trypsin or trypsin-like proteases from gill epithelial cells may protect these animals from gill bleeding following injuries. In this paper we identified the release of three different trypsins from fish gills into water under stress or injury, which have tenfold greater serine protease activity compared to bovine trypsin. We found that these trypsins activate the thrombocytes and protect the fish from gill bleeding. . . In conclusion, we believe that the gills are evolutionarily selected to produce trypsin to activate PAR2 on thrombocyte surface and protect the gills from bleeding. We also speculate that trypsin may also protect the fish from bleeding from other body injuries due to quick contact with the thrombocytes. Thus, this finding provides evidence for the role of trypsins in primary hemostasis in early vertebrates.

My take: Evolution is a highly conservative process: Once it finds something that works, it uses it over and over. So here the researchers have found a mechanism that protects fish, using enzymes commonly found in vertebrates. Trypsins are used in digestion among mammals and other vertebrates. The implication is that the last common ancestor of modern fish and mammals — a water-dwelling animal that looked like a present-day fish — had these trypsins, and that they were important in preventing blood loss. On the surface, you wouldn’t expect to see an enzyme used for digestion to have a role in stopping blood loss, but evolution doesn’t care about what humans would expect.

An Ultrasound Assisted Anchoring Technique (BoneWelding Technology) for Fixation of Implants to Bone – A Histological Pilot Study in Sheep From the Open Orthopaedics Journal abstract:

The BoneWelding® Technology offers new opportunities to anchor implants within bone. The technology melted the surface of biodegradable polymer pins by means of ultrasound energy to mould material into the structures of the predrilled bone. Temperature changes were measured at the sites of implantation in an in vitro experiment. In the in vivo part of the study two types of implants were implanted in the limb of sheep to investigate the biocompatibility of the method … Results demonstrated mild and short temperature increase during insertion. New bone formed at the implant without evidence of inflammatory reaction. The amount of adjacent bone was increased compared to normal cancellous bone. It was concluded that the BoneWelding® Technology proved to be a biocompatible technology to anchor biodegradable as well as titanium-PLA implants in bone.

My take: The bone-implant interface is tricky because bone is a living tissue, changing, growing and breaking down, with microscopic pores. Fusing an implant tightly to the bone helps it take hold. BoneWelding was recognized as one of the best spine technologies for 2009 by Orthopedics This Week, a trade publication.

BoneWelding is the product of a Swiss firm, SpineWelding AG. Other Best Spine Technologies winners include San Diego-based NuVasive, for its XLIF (eXtreme Lateral Interbody Fusion) technology. Carlsbad’s Alphatec Spine also won for its GLIF – Guided Lateral Interbody Fusion technology.