The increased fractional clearance of albumin in nephrotic states has long been attributed to glomerular permselectivity dysfunction. Using radiolabeled rat serum albumin, transferrin, IgG, and polydisperse Ficoll, this study investigated the changes in their in vivo fractional clearance in puromycin aminonucleoside nephrosis and anti-glomerular basement membrane glomerulonephritis. In control rats the lack of charge selectivity was confirmed by the demonstration that carboxymethyl Ficoll (valence ϳ؊39) had the same fractional clearance as uncharged Ficoll. Both diseases exhibited similar effects on fractional clearance measurements suggesting an underlying common mechanism. In disease, there was good agreement between the fractional clearance of proteins determined by radioactivity as compared to those determined by radioimmunoassay. A small increase in the fractional clearance for IgG was evident in disease as compared to controls, which mirrored the change in the equivalent size Ficoll, suggesting that the increase is because of the development of a small proportion of large pores in the glomerular capillary wall. There was no increase, however, in the fractional clearance of Ficoll of equivalent size to albumin in either disease, yet the fractional clearance of the albumin increased by 12 to 14 times as determined by radioactivity and 4500 to 6600 times as determined by radioimmunoassay. This study demonstrates that glomerulonephritis is not a disease associated with changes in glomerular permeability to albumin but is because of alterations in albumin processing by cells distal to the glomerular basement membrane. It is also apparent that approaches to glomerular pathology and proteinuria as risk factors in renal disease must be reassessed. (Am J Pathol 2001, 159:1159 -1170)
BackgroundMoisturizers are topical products designed to improve and maintain the skin barrier function and to help prevent dry skin.Materials and methodsA new moisturizer (Ceramide cream) was formulated containing ingredients which mimic the skin’s own natural moisturizing systems. Corneometry was performed at baseline, 2, 4, 6 and 24 hours following a single application of Ceramide cream to healthy skin, and compared to three reference moisturizers available over-the-counter, and placebo. Transepidermal water loss (TEWL) was also measured following a single application of Ceramide cream compared to baseline, and its safety was assessed by repeat insult patch test, ophthalmologist and pediatric testing.ResultsA single topical application of either the Ceramide cream or the three reference moisturizers resulted in a significant increase in skin hydration over time (P<0.001). The placebo cream did not significantly increase skin hydration at any time point. At 24 hours post-application, skin hydration measured for Ceramide cream was significantly greater (P<0.05) than that measured for all three of the reference moisturizers tested. Ceramide cream was also found to significantly decrease TEWL (P<0.001) over 24 hours, and was shown to be non-sensitizing to the skin of both adults and children and non-irritating to the skin, eyes and related eye area.ConclusionCeramide cream increases skin hydration and improves barrier function which may make it suitable for use on dry skin.
Recent studies, using low-temperature perfusion of rat kidneys, have claimed the existence of renal charge selectivity simply on the basis of the differential excretion rates of uncharged Ficoll and charged proteins. To test for the existence of charge selectivity in vivo, we examined the clearance of negatively charged Ficoll compared with uncharged Ficoll. A short-term approach to steady state was used to study the fractional clearances. Relative clearances were also examined using an osmotic pump technique where the tracers reach a steady-state value in conscious rats after 7 days. Carboxymethyl Ficoll was stable during filtration and renal passage, was not taken up by the kidneys, and did not bind to plasma proteins. There was no significant difference in the fractional clearance of molecules with radius of 36 A for Ficoll (fractional clearance = 0.048 +/- 0.038, n = 5) and negatively charged carboxymethyl Ficoll (fractional clearance = 0.028 +/- 0.019, n = 5). For molecules with radii greater than 36 A, carboxymethyl Ficoll had facilitated clearance with respect to uncharged Ficoll [for example, at a radius of 60 A fractional clearance for Ficoll = 0.0012 +/- 0.0005 (n = 5), whereas that for carboxymethyl Ficoll = 0.015 +/- 0.005 (n = 5)]. Renal function was not compromised by carboxymethyl Ficoll as uncharged Ficoll in urine exhibited similar hydrodynamic size profiles when studied in the presence of excess unlabeled carboxymethyl Ficoll. The facilitated clearance of negatively charged Ficoll with respect to uncharged Ficoll reveals a property of the capillary wall, which has been previously observed with other nonproteinaceous polyanions. This study demonstrates that the glomerular capillary wall is not charge selective in the form of excluding negatively charged Ficoll. However, the charge properties of the capillary wall may influence the facilitated transport of charged Ficoll compared with uncharged Ficoll.
Atopic eczema is one of the most common skin disorders in young children and also affects adults. Staphylococcus aureus infection is the most frequent complication of atopic eczema and is involved in the worsening of the disease. Antibiotic therapy against S. aureus has been an important component of treatment for atopic eczema but there are concerns about antibiotic overuse and increasing bacterial resistance. This has led some clinicians to recommend the use of homemade remedies such as bleach baths as an adjunctive treatment for patients with infected atopic eczema, despite the fact that there have been few published studies in this area. Balancing safety concerns with efficacious treatment is of particular importance in the paediatric population. This review discusses the historical use of bleach in medicine as well as its recent use for atopic eczema. Further, the chemistry and safety of bleach as well as alternative therapies are examined.
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