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Background Alternatives to room temperature storage of platelets (PLTs) are of interest to support blood banking logistics. The aim of this study was to compare the presence of biologic response modifiers (BRMs) in PLT concentrates stored under conventional room temperature conditions with refrigerated or cryopreserved PLTs. Study design and methods A three-arm pool-and-split study was carried out using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were as follows: room temperature (20-24°C), cold (2-6°C), and cryopreserved (-80°C with DMSO). Liquid-stored PLTs were tested over a 21-day period, while cryopreserved PLTs were tested immediately after thawing and reconstitution in 30% plasma/70% SSP+ and after storage at room temperature. Results Coagulation factor activity was comparable between room temperature and cold PLTs, with the exception of protein S, while cryopreserved PLTs had reduced Factor (F)V and FVIII activity. Cold-stored PLTs retained α-granule proteins better than room temperature or cryopreserved PLTs. Cryopreservation resulted in 10-fold higher microparticle generation than cold-stored PLTs, but both groups contained significantly more microparticles than those stored at room temperature. The supernatant from both cold and cryopreserved PLTs initiated faster clot formation and thrombin generation than room temperature PLTs. Conclusion Cold storage and cryopreservation alter the composition of the soluble fraction of stored PLTs. These differences in coagulation proteins, cytokines, and microparticles likely influence both the hemostatic capacity of the components and the auxiliary functions.

Cancer is a major cause of death in western societies. Overall, there has been no decline in the incidence and little improvement in survival for twenty years. Hundreds of millions of dollars are regularly spent on cancer research. It is argued that much research effort is misdirected as a consequence of a limited view of the nature of the cancer process and the influences on it. Preoccupation with a nineteenth century view of the genesis of cancer and a twentieth-century high-technology approach to treatment has prevented the proper exploration of the determinants of cancer, and the development of different therapeutic modes. Several models of the cancer process are examined. A model which considers human populations, human behaviour (including social and economic factors) and the interactive nature of the biologic response of living organisms to the environment is developed. Some of the implications of this model for research and therapy are discussed.

There are two major components in making new biologic medical countermeasures available for bio-defense and pandemic response: (1) the detection/discovery of effective counter- measures, and (2) their subsequent Process Development (PD) and manufacture. PD and manufacturing, however, are often the most costly and time-consuming parts of the process, potentially taking years and costing hundreds of millions to billions of dollars. To address these long timelines, governments have historically stockpiled countermeasures for known biothreats. Unfortunately, this kind of stockpiling is very expensive, and does not provide protection against novel threats. Fortunately, there currently exist many new technologies that, when combined strategically, have the potential to significantly reduce the time and cost associated with the PD and manufacturing of biologic countermeasures. Drug Dev Res 70:288-295, 2009. r 2009 Wiley-Liss, Inc.

Background: We evaluated in a canine duraplasty model how specific differences in device physicomechanical properties, porosity, and crosslinking influenced the biological performance of three processed collagen dural substitutes. Methods: Three collagen dural substitutes were studied: Dura-Guard, DuraGen, and Durepair. The initial strength, stiffness, and suture retention force were measured using standard mechanical test methods. The relative pore sizes of each device were assessed with a scanning electron microscope. Differential scanning calorimetry was used to measure their respective collagen denaturation temperatures. The biologic response and performance of the materials were evaluated via an acute (1 month) and long-term (3 and 6 months) canine bilateral duraplasty study. Results: The mechanical properties of Dura-Guard and Durepair were similar to native dura. We could not quantify the mechanical properties of DuraGen because of its fragile nature. The denaturation temperature of DuraGen and Dura-Guard differed significantly from that reported for native collagens. The denaturation temperature of Durepair was comparable with the values reported for native collagens. All three materials were tolerated well by the animals. DuraGen did not maintain its structural integrity beyond 1 month. Dura-Guard and Durepair persisted for 6 months. Durepair was populated by fibroblasts and blood vessels, whereas Dura-Guard was not. Conclusions: The three dural substitutes tested were found to be safe and effective in healing surgically created defects in the dura mater. Although each of these dura substitutes are composed of collagen, differences in the collagen source and processing influenced device physicomechanical properties, porosity, and the nativity of the collagen polymer. These measured differences influenced device intraoperative handling and installation as well as the post-operative biological response, where differences in device resorption, cell penetration, vascularization, and collagen remodeling were observed. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007

The purpose of this study was to define the surface properties of prepared titanium (Ti) disks, which served as a model system, and to contrast the biologic response of MG63 cells exposed to Ti disks with different levels of surface roughness. The surface properties interact with each other, resulting in a change of other surface qualities in addition to roughness due to the surface roughening procedure. The machined Ti disks were roughened by sandblasting and electric glow discharging. The surface properties of the Ti specimens were inspected through a comprehensive surface analysis. MG63 cell behaviors were compared along with cell number, alkaline phosphatase (ALP) activity, Runx2 gene expression, and type I collagen production. Statistics were evaluated, using analysis of variance (ANOVA). The sandblasted Ti disks demonstrated well-controlled surface roughness features and meaningful average roughness ranges, including the surface roughness of the "modern" microrough implant, used clinically. With increasing Ti surface roughness, the cell number decreased, while the ALP activity, type I collagen production, and Runx2 gene expression increased significantly. The rougher the Ti surface was, the sooner the Runx2 gene was expressed. Based on these results, we suggest that the microrough Ti surfaces of the 1-3 mum range may contribute effectively to osteogenic differentiation and proliferation in MG63 cells.

The immunopathology of rheumatoid arthritis (RA) is now better understood, and this knowledge has been translated into more effective therapy with biologic response modifiers. The first group of biologic response modifiers are the tumor necrosis factor inhibitors. There efficacy in controlling RA has been such that remission is now the goal of RA management. As with any patient treatment, safety is an issue; patients will need ongoing monitoring for infections, tumors, and other rare complications.

Advances in the understanding of neuroblastoma biology have helped distinguish those patients who require maximum therapy from those who do not. However, management of children with advanced disease remains a significant problem. New more intensive multiagent chemotherapy, ablative chemoradiotherapy with bone marrow transplantation, radiolabelled monoclonal antibody technology and a host of biologic response modifiers are currently being intensively studied. Nevertheless, surgery remains crucial for diagnosis, for providing adequate tissue for biological and histopathologic staging, for primary and secondary resections as well as restaging after therapy. Major surgical questions remain to be addressed in cooperative group studies.

This paper provides a summary of a recent International Association for Dental Research symposium, “Oral infections in the immunocompromised host.” Speakers addressed current science relative to the host defense system (oral mucosal barrier, salivary gland function, use of biologic response modifiers), as well as characteristics of bacterial, fungal and viral pathogens. Avenues for future directions in laboratory and clinical research are proposed.

Whenever a foreign object is implanted in living tissue, a cellular response occurs. Sutures usually produce a mild response that varies in character with different materials. The cellular and tissue reaction can be evaluated by both morphologic and enzyme histochemical approaches. Such studies assist in understanding suture absorption and the degree of inertness in tissues associated with the various suture materials. In addition, the in vivo measurement of breaking strength retention provides information on suture safety. Such studies also assist in the development of improved suture materials for various surgical applications.