Prenatal causes of kidney diseases

Deleterious environmental factors during pregnancy influence fetal development and increase therisk of cardiovascular and kidney disease in adult offspring. Undernutrition, protein restriction,excess salt, corticosteroids, or placental insufficiency disturb kidney development, causing a lowernumber of nephrons (referred to as nephron underdosing). This in turn leads to hypertension andaccelerated loss of kidney function in the adult life of the offspring. The nephron underdosingcan be observed with or without intrauterine growth restriction. A lower number of nephrons havebeen confirmed in humans with hypertension

Degradation studies of hydrophilic, partially degradable and bioactive cements (HDBCs) incorporating chemically modified starch

The degradation rate in Hydrophilic, Degradable and Bioactive Cements (HDBCs) containing starch/cellulose acetate blends (SCA) is still low. In order to increase degradation, higher amounts of starch are required to exceed the percolation threshold. In this work, gelatinization, acetylation and methacrylation of corn starch were performed and assessed as candidates to replace SCA in HDBCs. Formulations containing methacrylated starch were prepared with different molar ratios of 2-hydroxyethyl methacrylate and methyl methacrylate in the liquid component and the amount of residual monomer released into water was evaluated. The concentration of reducing sugars, percentage of weight loss and morphologic analyses after degradation all confirmed increased degradation of HDBC with alpha-amylase, with the appearance of pores and voids from enzymatic action. Methacrylated starch therefore is a better alternative to be used as the solid component of HDBC then SCA, since it leads to the formation of cements with a lower release of toxic monomers and more prone to hydrolytic degradation while keeping the other advantages of HDBCs.The authors acknowledge to Foundation for Science and Technology (FCT), who supported this study through funds from project Concept2Cement (POCTI/CTM/60735/2004)

Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young

Large animal models of cardiovascular disease

The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone-formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease. Copyright (c) 2016 John Wiley & Sons, Ltd

Comparative and morphological analysis of commonly used autografts for anterior cruciate ligament reconstruction with the native ACL: An electron, microscopic and morphologic study

Ligaments and tendons are similar in composition but differ in proportion and arrangement. Tendons are being used as grafts for the ACL reconstruction. Their microscopic structure has not been sufficiently studied and compared to the native ACL. A null hypothesis was declared stating that the anterior cruciate ligament should be histological, morphologically and functionally different from the tendon grafts used for ACL reconstruction. We investigated similarities and differences of the structure of ACL and tendons used as a graft tissue for ACL reconstruction. In this study, standardized samples of quadriceps, hamstrings (semitendinosus and gracilis) and patellar tendons, and the ACL were harvested from 26 autopsies (average age 36.4) and were investigated using light and electron microscopy, immunohistochemistry and morphometry. The thickness of the collagen fibrils, collagen organization and diameter, the fibril/interstitium ratio, density of fibroblasts and blood vessels, and distribution of the collagen type I, III and V fibrils were analyzed. The semitendinosus showed the highest density of fibroblasts and blood vessels, while the gracilis the highest fibril/interstitium ratio. No differences regarding the thickness of collagen fibrils and distribution of fibrils were found. The ACL had the highest concentration of type III and V collagen fibrils as well as elastic fibers. The histological and ultrastructural appearance of the ACL differs from those of the tendons used as graft, for ACL reconstruction. Its ultrastructure is varied and complex, with its collagen fibers bundles lying in many directions. © 2008 Springer-Verlag

Degenerative changes of the interface membrane as a possible reason for prosthesis loosening

Objective: The aim of the present study was to perform a comparative evaluation of septic and aseptic interface membranes, assessing histological features, inflammatory infiltrate, and expression of inflammatory cytokines. Methods: Septic and aseptic interface membranes from 102 patients were examined by histology, histochemistry, and immunohistochemistry (tissue arrays). The cell subpopulations were characterized by quantification of CD3, CD4, CD8, CD20, and CD163 positive cells. Additionally, a semiquantitative evaluation of inflammatory cytokines (TNFa, TGF-ß1, IL-1, IL-6, CRP, MMP-1, MMP-6) was performed to complete the analysis of inflammatory infiltrates. Results: The histological analysis revealed three different types of aseptic interface membranes: wear particle, degenerative, and mixed type. The expression of inflammatory molecules did not differ between septic and wear particle interface membranes. Significantly lower expression of cytokines, MMPs and CRP was observed, however, in degenerative interface membranes compared to other types. No expression of TNFa was observed in the degenerative interface membranes. Over 88% of patients with degenerative interface membranes had had a clinical record of osteoarthritis. Conclusion: Aseptic interface membranes were represented by wear particle, degenerative and mixed type. The expression of inflammatory factors in wear particle type is similar to this in septic membranes and can contribute to the bone destruction and prosthesis loosening. These factors seem not to play a major role in the degenerative membranes