Molecules with vitamin K activity are important for optimal bone health. The major compound of this group in bone is vitamin K1 (phylloquinone), which is derived exclusively from plant foods in the diet. Vitamin K1 is absorbed along with dietary fat from the small intestine and transported by chylomicrons in blood. In serum obtained after an overnight fast from healthy men more than half of the vitamin K1 was recovered from the density fraction that contains chylomicrons and chylomicron remnants (CR), and only a quarter was associated with the major lipoprotein in serum, low density lipoprotein. The concentration of vitamin K1 in serum is closely related to the triglyceride concentration. Another determinant of vitamin K1 concentration in serum is the presence of specific variants of apolipoprotein E (apoE). ApoE is a small protein through which the vitamin K-rich CR bind to lipoprotein receptors. The three most common variants of apoE promote CR clearance from circulation with very different efficiency, in the order E2>E3>E4. The variant that promotes CR clearance best is associated with low vitamin K1 concentration in serum and increased response to vitamin K antagonists. Vitamin K1 concentration in serum is linked to vitamin K status of bone. The bone protein osteocalcin tends to be less completely carboxylated in people with low vitamin K concentrations in serum. Many hemodialysis patients with a history of bone fractures have indications of poor vitamin K status. The same patients also appear to have a greatly increased prospective bone fracture risk.
Imbalances in epithelium-matrix interactions have been discussed as a pathomechanism in ulcerative colitis, causing a colonic mucosal barrier dysfunction. Laminin, the major noncollagenous component of the basement membrane, plays a role in epithelial basal lamina formation and promotes differentiation of human enterocytes. We therefore investigated the distribution of laminin in ulcerative colitis affected colonic tissues. Tissue specimens from both affected and nonaffected colonic regions were obtained from ten patients with ulcerative colitis during colonoscopies or operations. Healthy tissue from five patients with colorectal cancer was used as control. After histological classification, the localization and distribution of the basement membrane associated extracellular matrix proteins were determined by immunohistochemistry. Paraffin-embedded sections were incubated with antibodies against laminin and type IV and V collagen. No positive immunoreactivity against laminin was found in most of the epithelial basement membranes surrounding the crypts in affected colonic tissues, without involvement of the subendothelial structures. In contrast, a type IV and V collagen accumulation occurred in all these tissue samples. The lack of laminin in combination with an overexpression of type IV and V collagen, as reported for the first time in this paper, leads to changes in basement membrane structure. These findings indicate that the three-dimensional network of the colonic epithelial basement membrane and its function are seriously disturbed in exacerbating ulcerative colitis. This provides new insights into the importance of cell-matrix interactions for physiological and pathological mechanisms in the etiology of ulcerative colitis.
Precision cut liver slices from humans and rats were used to investigate the covalent binding of xenobiotics to the DNA by means of the (32)P-postlabeling technique. Human liver slices were incubated with the structurally related steroid hormones chlormadinone acetate (5 mu g/ml), cyproterone acetate (0.01-5 mu g/ml), megestrol acetate (5 mu g/ml), and the positive control 2-aminofluorene (0.01-5 mu g/ml), which is known for its marked ability to form DNA-adducts in vivo. Rat liver slices were incubated with cyproterone acetate in concentrations of 0.1, 1, and 5 mu g/ml. The functional viability and metabolic activity of the slices were shown to be sufficiently maintained during the incubation time by measurement of the intracellular K(+)-content and the metabolic turnover of the model substrate 7-ethoxycoumarin, respectively. All three test substances and the control induced DNA-adducts in human liver slices, however, with a different adduct pattern. While the total DNA-adduct levels obtained with cyproterone acetate and megestrol acetate were in the same order of magnitude (on average 1000 DNA-adducts/10(9) nucleotides after incubation with 5 mu g /ml), the relative adduct labeling calculated for chlormadinone acetate was about 400. Following in vitro incubation of rat liver slices with cyproterone acetate, the relative adduct labeling values increased proportionally with increasing concentrations and added linearily to in vivo generated DNA-adducts. At the level of liver slices, different DNA-adduct patterns were induced by cyproterone acetate in rat and man. In contrast to the finding of others, using rat hepatocytes, the relative adduct labeling values of cyproterone acetate and megestrol acetate were in the same order of magnitude after incubation with human liver slices. The present study indicates that liver slices are a useful tool to investigate the in vitro DNA-adduct inducing potential of xenobiotics.
advance the present, fully group-IV-based room temperature light-emitting devices [6] or photodetectors. [7,8] For many of these applications, the Ge concentrations x for the thick but pseudomorphic Si 1-x Ge x films (TPFs) should be ideally in the range between 50% and 100%, to ensure, e.g., large enough band offsets between the Si and SiGe layers. [5,9] However, the literature reports mainly focus on TPFs with low Ge contents, x < 0.5, [10][11][12][13][14][15][16][17][18] with only a few exceptions for which the critical thickness for pronounced relaxation was evaluated for single Ge concentrations of about 55%. [11,17] In general, during the growth of strained epitaxial layers, the strain energy increases with the square of the misfit strain and linearly with the layer thickness. Thus, TPFs must release the inherent strain energy by either plastic or elastic relaxation above a misfit strain-dependent critical thickness (t c ). The former via the insertion of misfit dislocations, [19] the latter via an increase in surface energy, i.e., by forming 3D objects, such as surface undulations, quantum dots, or wires. [20] A general trend confirmed by this work is that for sufficiently high growth temperatures and beyond t c for flat film growth, lower misfits lead to the formation of dislocations (plastic relaxation), while for high misfits, typically 3D nanostructures form via elastic relaxation. [12,21,22] Along similar lines, a mixture of low-and high-temperature growth can be used to produce flat relaxed films, starting from low-temperature growth to favor dislocation insertion, followed by high-temperature growth to increase the film quality. [23][24][25] Equilibrium theory for t c of TPFs was first developed in the 70s [26,27] but did not consider that, in reality, the growth of TPFs, e.g., by molecular beam epitaxy (MBE), happens far from thermal equilibrium. Hence, the kinetic suppression of either dislocation nucleation or quantum dot formation at low growth temperatures (T G ) explains why for Ge concentrations x < 55% experimentally found values of t c exceed those predicted by equilibrium theory by about an order of magnitude. [11,17,[28][29][30] Along the same lines, it was shown that supersaturation in the wetting layer (WL) occurs before the nucleation of quantum dots or wires during the epitaxial deposition of pure Ge thin films. [31] However, at T G ¼ 700 °C, the supersaturation amounts to only %0.14 nm of Ge, and quantum dot formation occurs already after the deposition of 0.6 nm. [32] Notably, the onset of quantum dot formation can be accelerated or delayed by increasing or decreasing T G , respectively. [33,34]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.