SignificanceHuman kidneys contain ∼2 x 106 glomeruli that produce ∼180 L per day of primary filtrate. Downstream tubules reabsorb most of the water, salt, and desirable low-molecular weight substances, leaving 1 to 2 L per day of urine containing undesirable waste products. Currently, most investigators think that the primary filtrate is low in protein because fluid exiting the glomerulus passes through slits spanned by a diaphragm that acts as a low-porosity molecular sieve. Our experiments challenge this view; they show that size-dependent permeation into the glomerular basement membrane and into a gel-like coat that covers the slits, together with saturable tubular reabsorption, determines which macromolecules reach the urine. The slit diaphragm is essential for capillary structure but may not directly determine glomerular size selectivity.
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. SCOPE AND SIGNIFICANCESilicone gel sheeting (SGS) has been used in scar therapy for over 30 years, during which its efficacy has been the subject of numerous clinical evaluations. 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. As such, topical silicone gel treatments seem to remain the first point of clinical recommendation in scar management. This article aims to review a breadth of literature to gain an insight not only into how, but also 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 as a comparison. TRANSLATIONAL RELEVANCESilicone has been used for more than 30 years in the treatment of cutaneous scars.1 New formulations and formats of silicone gel products are becoming available for use in the treatment of scarring resulting from surgery, burns, and other skin injuries requiring hospital treatment.
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.The importance of free-living protozoa, such as amoebae, as environmental reservoirs of food-borne pathogens is becoming increasingly recognized (1,6,9,18). Such interactions may also have highly significant physiological implications, as amoebic passage of Legionella pneumophila enhanced bacterial virulence (3) and could resuscitate viable but nonculturable cells (20). Salmonella enterica serovars Typhimurium and Dublin have been shown to survive within Acanthamoeba polyphaga and Acanthamoeba rhysodes (5,22), and induction of fis transcription, indicative of bacterial proliferation within contractile vacuoles, has been reported (3). The role of the Salmonella pathogenicity island 1 (SPI-1)-encoded type III secretion system (T3SS-1), which mediates forced bacterial uptake via subversion of actin dynamics, is unclear; however, an S. enterica serovar Dublin ⌬hilA mutant lacking a key transcriptional activator of SPI-1 entered and survived within A. rhysodes at a level similar to that of the parent strain (22). A second type III secretion system encoded by SPI-2 (T3SS-2) and the PhoPQ two-component regulatory system are known to play key roles in the intracellular survival of Salmonella in mammalian cells, but their roles in interactions with protozoa have not been reported. In this study we investigated the roles of T3SS-1, T3SS-2, and PhoP in entry and survival of S. enterica serovar Typhimurium in A. polyphaga using defined mutant strains. Additionally, we quantified transcription of the S. enterica serovar Typhimurium SPI-1 gene sipC and the SPI-2 gene sseC (which encode components of the type III secretion translocon) within A. polyphaga.A gentamicin protection assay modified from that used to quantify Salmonella invasion of avian cells was used to assess uptake and intracellular survival in Acanthamoeba polyphaga Linc-1 grown in axenic culture in peptone-yeast extract-glucose medium (PYG) (1, 2). Amoebae were grown to 5 ϫ 10 6 cells per ml initially in flasks and then in 24-well plates. S. enterica serovar Typhimurium strain F98 and previously described variants with mutations in the SPI-1 gene spaS and in the SPI-2 gene ssaU (genes well characterized for changes in their phenotype for virulence, cell invasion, and survival within macrophages [10,11,23]) and in phoP (13) were grown at 37°C in Luria-Bertani (LB) broth with shaking at 150 rpm to late logarithmic phase and added to amoebae at a multiplicity of infection (MOI) of 10. After 1 h of incubation at 37°C, the plates were centrifuged at 50 ϫ g for 5 min. The medium was removed from the plates and replaced with PYG containing gentamicin sulfate at 100 g ml Ϫ1 . ...
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