A bone-like precoating strategy for implants: collagen immobilization and mineralization on pure titanium implant surface.

Many surface modification strategies are currently of interest in improving integration of implants to bone. An in vitro precoating of a bone-like mineralized layer of immobilized collagen on the implant surface is a potentially valuable approach to improve host acceptance of the implant. The goal of this investigation was to develop a method to precoat in vitro a bone-like mineralized collagen layer on a pure titanium dental implant surface. The study was conducted on acid-etched and nonetched surfaces of screw implants. Initially, a procedure was standardized to self-assemble collagen from a collagen solution. In subsequent experiments, the implant was also placed inside the solution, and after 3 days, collagen was found to be coated on the implant surface. Mineralization of the collagen gel as well as collagen coating on the implant was carried out by calcium phosphate precipitation from a mineralizing solution of calcium chloride containing polyvinyl phosphonic acid and polyaspartic acid, which served as polyanionic additives to help disperse the precipitation and template mineral nucleation. The implant was kept in the mineralizing solution and maintained for 2 weeks in an incubator at 37 degrees C with a phosphate vapor phase generated from a vial containing dihydrogen ammonium phosphate in the incubator. Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the coated layer to be a biomimetic bone-like mineralized type 1 collagen. Initial studies using osteoblast-like cells indicated cellular attachment on the modified surface. The method appears to be a promising way to generate in vitro a bone-like layer on the implant surface.

Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo.

We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust neutrophil chemorepulsion in microfluidic gradients of interleukin-8 (IL-8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin-sensitive and dependent on phosphoinositide-3 kinase, RhoGTPases, and associated proteins. Perturbation of neutrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL-8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation.

Impaired microvascular endothelial function in vitamin D-deficient diabetic nephropathy patients.

AIMS: This study aims to compare microvascular endothelial function between vitamin D-deficient and nondeficient groups of patients with diabetic nephropathy. Serum levels of the inflammatory marker high-sensitivity C-reactive protein (hsCRP) were also measured. METHODS: This prospective cross-sectional study involved 70 patients with diabetic nephropathy; 40 were categorized into the group with nondeficient serum 25-hydroxyvitamin D levels [25(OH)D >50 nmol/l], whereas 30 patients were categorized to the group with deficient serum 25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and sodium nitroprusside were used to determine endothelium-dependent and independent vasodilatation. RESULTS: Mean age of patients was 56.7 ± 3.8 years; 50 were men, whereas 20 were women. Mean serum 25(OH)D in the vitamin D-nondeficient group was 69.4 ± 2.9 nmol/l; the level in the vitamin D-deficient group was 42.1 ± 1.3 nmol/l, P < 0.001. Endothelium-dependent vasodilatation was lower in the vitamin D-deficient group compared with the vitamin D-nondeficient group (23.6 ± 2.7 versus 37.3 ± 3.8 arbitrary units, P = 0.004). No significant differences were observed between the two groups in their hsCRP levels, mean age, estimated glomerular filtration rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and glycosylated haemoglobin. CONCLUSION: Microvascular endothelial function was significantly reduced in diabetic nephropathy patients with deficient vitamin D levels compared with those with nondeficient levels.

The GP120 molecule of HIV-1 and its interaction with T cells.

The gp120 molecule of HIV-1 is a glycoprotein that is part of the outer layer of the virus. It presents itself as viral membrane spikes consisting of 3 molecules of gp120 linked together and anchored to the membrane by gp41 protein. Gp120 is essential for viral infection as it facilitates HIV entry into the host cell and this is its best-known and most researched role in HIV infection. However, it is becoming increasingly evident that gp120 might also be facilitating viral persistence and continuing HIV infection by influencing the T cell immune response to the virus. Several mechanisms might be involved in this process of which gp120 binding to the CD4 receptor of T cells is the best known and most important interaction as it facilitates viral entry into the CD4+ cells and their depletion, a hallmark of the HIV infection. Gp120 is shed from the viral membrane and accumulates in lymphoid tissues in significant amounts. Here, it can induce apoptosis and severely alter the immune response to the virus by dampening the antiviral CTL response thus impeding the clearance of HIV. The effects of gp120 and how it interacts and influences T cell immune response to the virus is an important topic and this review aims to summarize what has been published so far in hopes of providing guidance for future work in this area.