Poxviruses: past, present and future

The analysis of poxvirus genomes is complex, in part, because of their size (130-360 kb) and the fact that gene content is variable; a common set of 49 genes has been found in all sequenced poxviruses and an additional 41 genes are also present in all sequenced orthopoxviruses. As a group, poxviruses have a very broad range of eukaryotic hosts (including mammals, birds, reptiles and insects) and many poxvirus genes are associated with blocking host anti-viral responses. One consequence of this is that many poxvirus genes are not essential for growth in tissue culture and that extensive passaging in vitro results in the accumulation of mutations, including deletions that result in loss of gene function. Here, we review various comparative analyses of the poxviruses including gene prediction, gene conservation and function, genome organization, and poxvirus taxonomy and evolution.     

Artificial skin: past, present and future

The integrity of the skin should be restored as soon as possible whenever the skin gets wounded. Recent research has revealed some of the complex pathways in wound healing. Based on this knowledge, researchers have been looking for better skin substitutes to treat difficultly healing or large wounds. Some of these highly sophisticated wound dressings, also known as bio-dressings, contain material of human or animal origin, e.g. cultured skin cells. Although the ideal skin substitute has not been established yet, the currently available bio-dressings help clinicians close difficultly healing skin wounds.     

The macrophage: past, present and future

As we approach the centenary of Elie Metchnikoff's Nobel Prize (1908), it is opportune to reflect upon the history of macrophage immunobiology, take stock of current knowledge and anticipate questions for the future. Starting from his appreciation of phagocytosis as an important determinant of host defence against infection and injury, we have learned a great deal about the distribution of macrophages throughout the body, their heterogeneous phenotype and complex functions in tissue homeostasis as well as in innate and acquired immunity. Recent discoveries of Toll-like and other plasma membrane, vacuolar and cytosolic recognition molecules have brought the macrophage and closely related dendritic cells to the centre of immunologic attention, but many earlier discoveries of their cellular and molecular properties have laid a broader foundation to the appreciation of their remarkable plasticity and adaptability to local and systemic cues. Discoveries of pro-inflammatory mediators such as TNF and other secretory products have provided valuable insights into the role of macrophages in many acute and chronic disease processes, and led to the development of effective therapeutics. Much remains to be discovered regarding both their specific functions and by study of their general cellular properties, in vitro and in vivo.     

Gleason grading: past, present and future

In 1966 Donald Gleason developed his grading and scoring system for prostatic adenocarcinoma. This classification was refined in 1974 and gained almost universal acceptance, being classified as a category 1 prognostic parameter by the College of American Pathologists. Modifications to the classification were recommended at a conference convened by the International Society of Urological Pathology (ISUP) in 2005. This modified classification has resulted in a significant upgrading of tumours, although some studies have shown a greater concordance between needle biopsy and radical prostatectomy scores when compared to classical Gleason (CG) grading. The ISUP consensus conference recommended that for needle biopsies higher tertiary patterns should be incorporated into the final Gleason score, and this has been correlated with biochemical failure, tumour volume and mortality. Recently the validity of including cribriform glands as a component of Gleason pattern 3 has been questioned and it has been recommended that all tumours showing cribriform architecture should be classified as Gleason pattern 4. The recommendations arising from the 2005 Consensus Conference were largely unsupported by validating data, yet this new grading system has achieved widespread usage. It is unfortunate that recent suggestions for further modification are similarly lacking in supporting evidence. In view of this it is recommended that the Modified Gleason Scoring Classification should continue to be utilized in its original (2005) format and that any future alterations should be implemented only when mandated by tumour-related outcome studies.     

Liposomes and skin: past, present, future

tAmong various approaches to intra- and percutaneous administration of drugs, e.g. application of patches, ointments, iontophoresis, electroporation, the use of lipid vesicles like liposomes and niosomes presents numerous advantages. They are not toxic or invasive, may deliver hydrophobic and/or hydrophilic molecules, and the size of the transported molecule is not a limiting factor. Liposomes are obtained with natural amphiphilic lipids whereas niosomes are composed of synthetic amphiphilic molecules. These microscopic vesicles contain from one to several concentric lipid bi-layers with intercalated aqueous compartments. Trans-epidermal penetration of the vesicles is proportional to the "fluidity" of their lipids and their negative charge. Several drugs and cosmetics in this gallenic form are already commercially available and successfully used, presenting a better dose/effect ratio and provoking less side-effects.     

Leptospirosis vaccines: past, present, and future

It is well known that Leptospira vaccine prevents the disease. However specificity for serovars limits the efficacy of killed whole cell vaccines. Leptospiral antigens that induce cross-protective immunity to the various serovars are sought as new vaccine candidates. In this paper, we have summarized both past and current findings about leptospiral antigens that are conserved among pathogenic leptospires and that induce protective immunity in animal models. The full-length genome sequences of two Leptospira strains have been published and reverse vaccinology has been used to identify leptospiral vaccine candidates. Although humoral immunity is thought to be dominant in protection from leptospiral infection, a role for cell-mediated immunity is now being explored.     

Vascular access: past, present, and future

Vascular access is the Achilles' heel of hemodialysis. Current vascular access approaches for hemodialysis include arteriovenous (AV) fistula, AV graft, and central venous catheter. Strengths and weaknesses of each access type are described. New technology and procedures in introducing an access, monitoring access function, and salvaging a non-functioning access are also described.