Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules.

How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson's or Alport's proteinuric syndromes resulting from defects in GBM structural proteins (laminin ß2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm.

The Use of Silicone Adhesives for Scar Reduction.

Significance: This article discusses the history and developments of silicone gel sheeting (SGS) scar therapy. Furthermore, we review a breadth of literature to gain an insight into how and why topical silicone gels remain the favored treatment of medical experts in scar management. We also analyze an ever increasing number of alternative therapies claiming to provide enhanced scar reduction performance. Recent Advances: Topical silicone gel treatments seem to remain the first point of clinical recommendation in scar management. SGS has been used in scar therapy for over 30 years, during which its efficacy has been the subject of numerous clinical evaluations. Critical Issues: While the exact mechanisms by which SGS improves hypertrophic scars, keloid development and recovery are yet to be fully agreed upon, its ability to do so remains largely undisputed at present. However, there still is ongoing deliberation over the exact mechanism of action of silicone in improving a scar. At present it is likely that through occlusion of the scar site and hydration of the wound bed, the overactivity of scar-related cells is suppressed, and their activity normalized. Future Direction: The clinical support of topical silicone gel products, relative to all alternative scar therapies, is considered the internationally recommended first-line form of scar management, and favored by consensus among healthcare professionals. However, there still remains the need for further clinical evidence and a better understanding of the mechanism behind the benefit of silicone gel for use in the prevention of abnormal scarring.

The Salmonella pathogenicity island 2-encoded type III secretion system is essential for the survival of Salmonella enterica serovar Typhimurium in free-living amoebae.

Free-living amoebae represent a potential reservoir and predator of Salmonella enterica. Through the use of type III secretion system (T3SS) mutants and analysis of transcription of selected T3SS genes, we demonstrated that the Salmonella pathogenicity island 2 is highly induced during S. enterica serovar Typhimurium infection of Acanthamoeba polyphaga and is essential for survival within amoebae.