Comparison of the capacity of enamel matrix derivative gel and enamel matrix derivative in liquid formulation to adsorb to bone grafting materials.

BACKGROUND The use of an enamel matrix derivative (EMD) has been shown to enhance periodontal regeneration (e.g., formation of root cementum, periodontal ligament, and alveolar bone). However, in certain clinical situations, the use of EMD alone may not be sufficient to prevent flap collapse or provide sufficient stability of the blood clot. Data from clinical and preclinical studies have demonstrated controversial results after application of EMD combined with different types of bone grafting materials in periodontal regenerative procedures. The aim of the present study is to investigate the adsorption properties of enamel matrix proteins to bone grafts after surface coating with either EMD (as a liquid formulation) or EMD (as a gel formulation). METHODS Three different types of grafting materials, including a natural bone mineral (NBM), demineralized freeze-dried bone allograft (DFDBA), or a calcium phosphate (CaP), were coated with either EMD liquid or EMD gel. Samples were analyzed by scanning electron microscopy or transmission electron microscopy (TEM) using an immunostaining assay with gold-conjugated anti-EMD antibody. Total protein adsorption to bone grafting material was quantified using an enzyme-linked immunosorbent assay (ELISA) kit for amelogenin. RESULTS The adsorption of amelogenin to the surface of grafting material varied substantially based on the carrier system used. EMD gel adsorbed less protein to the surface of grafting particles, which easily dissociated from the graft surface after phosphate-buffered saline rinsing. Analyses by TEM revealed that adsorption of amelogenin proteins were significantly farther from the grafting material surface, likely a result of the thick polyglycolic acid gel carrier. ELISA protein quantification assay demonstrated that the combination of EMD liquid + NBM and EMD liquid + DFDBA adsorbed higher amounts of amelogenin than all other treatment modalities. Furthermore, amelogenin proteins delivered by EMD liquid were able to penetrate the porous surface structure of NBM and DFDBA and adsorb to the interior of bone grafting particles. Grafting materials coated with EMD gel adsorbed more frequently to the exterior of grafting particles with little interior penetration. CONCLUSIONS The present study demonstrates a large variability of adsorbed amelogenin to the surface of bone grafting materials when enamel matrix proteins were delivered in either a liquid formulation or gel carrier. Furthermore, differences in amelogenin adsorption were observed among NBM, DFDBA, and biphasic CaP particles. Thus, the potential for a liquid carrier system for EMD, used to coat EMD, may be advantageous for better surface coating.

Effect of bone graft density on in vitro cell behavior with enamel matrix derivative

OBJECTIVES Bone replacement grafting materials play an important role in regenerative dentistry. Despite a large array of tested bone-grafting materials, little information is available comparing the effects of bone graft density on in vitro cell behavior. Therefore, the aim of the present study is to compare the effects of cells seeded on bone grafts at low and high density in vitro for osteoblast adhesion, proliferation, and differentiation. MATERIALS AND METHODS The response of osteoblasts to the presence of a growth factor (enamel matrix derivative, (EMD)) in combination with low (8 mg per well) or high (100 mg per well) bone grafts (BG; natural bone mineral, Bio-Oss®) density, was studied and compared for osteoblast cell adhesion, proliferation, and differentiation as assessed by real-time PCR. Standard tissue culture plastic was used as a control with and without EMD. RESULTS The present study demonstrates that in vitro testing of bone-grafting materials is largely influenced by bone graft seeding density. Osteoblast adhesion was up to 50 % lower when cells were seeded on high-density BG when compared to low-density BG and control tissue culture plastic. Furthermore, proliferation was affected in a similar manner whereby cell proliferation on high-density BG (100 mg/well) was significantly increased when compared to that on low-density BG (8 mg/well). In contrast, cell differentiation was significantly increased on high-density BG as assessed by real-time PCR for markers collagen 1 (Col 1), alkaline phosphatase (ALP), and osteocalcin (OC) as well as alizarin red staining. The effects of EMD on osteoblast adhesion, proliferation, and differentiation further demonstrated that the bone graft seeding density largely controls in vitro results. EMD significantly increased cell attachment only on high-density BG, whereas EMD was able to further stimulate cell proliferation and differentiation of osteoblasts on control culture plastic and low-density BG when compared to high-density BG. CONCLUSION The results from the present study demonstrate that the in vitro conditions largely influence cell behavior of osteoblasts seeded on bone grafts and in vitro testing. CLINICAL RELEVANCE These results also illustrate the necessity for careful selection of bone graft seeding density to optimize in vitro testing and provide the clinician with a more accurate description of the osteopromotive potential of bone grafts.

Enamel matrix derivative and bone grafts for periodontal regeneration of intrabony defects. A systematic review and meta-analysis

OBJECTIVE The aim of the present systematic review and meta-analysis was to assess the clinical efficacy of regenerative periodontal surgery of intrabony defects using a combination of enamel matrix derivative (EMD) and bone graft compared with that of EMD alone. MATERIALS AND METHODS The Cochrane Oral Health Group specialist trials, MEDLINE, and EMBASE databases were searched for entries up to February 2014. The primary outcome was gain of clinical attachment (CAL). Weighted means and forest plots were calculated for CAL gain, probing depth (PD), and gingival recession (REC). RESULTS Twelve studies reporting on 434 patients and 548 intrabony defects were selected for the analysis. Mean CAL gain amounted to 3.76 ± 1.07 mm (median 3.63 95 % CI 3.51-3.75) following treatment with a combination of EMD and bone graft and to 3.32 ± 1.04 mm (median 3.40; 95 % CI 3.28-3.52) following treatment with EMD alone. Mean PD reduction measured 4.22 ± 1.20 mm (median 4.10; 95 % CI 3.96-4.24) at sites treated with EMD and bone graft and yielded 4.12 ± 1.07 mm (median 4.00; 95 % CI 3.88-4.12) at sites treated with EMD alone. Mean REC increase amounted to 0.76 ± 0.42 mm (median 0.63; 95 % CI 0.58-0.68) at sites treated with EMD and bone graft and to 0.91 ± 0.26 mm (median 0.90; 95 % CI 0.87-0.93) at sites treated with EMD alone. CONCLUSIONS Within their limits, the present results indicate that the combination of EMD and bone grafts may result in additional clinical improvements in terms of CAL gain and PD reduction compared with those obtained with EMD alone. The potential influence of the chosen graft material or of the surgical procedure (i.e., flap design) on the clinical outcomes is unclear. CLINICAL RELEVANCE The present findings support the use of EMD and bone grafts for the treatment of intrabony periodontal defects.

A new chromanone derivative isolated from Hypericum lissophloeus (Hypericaceae) potentiates GABAA receptor currents in a subunit specific fashion.

A phytochemical investigation of the lipophilic extract of Hypericum lissophloeus (smoothbark St. John's wort, Hypericaceae) was conducted, resulting in the isolation and identification of a new chromanone derivative: 5,7-dihydroxy-2,3-dimethyl-6-(3-methyl-but-2-enyl)-chroman-4-one (1). This compound was demonstrated to act as a potent stimulator of currents elicited by GABA in recombinant α1β2γ2 GABAA receptors, with a half-maximal potentiation observed at a concentration of about 4μM and a maximal potentiation of >4000%. Significant potentiation was already evident at a concentration as low as 0.1μM. Extent of potentiation strongly depends on the type of α subunit, the type of β subunit and the presence of the γ subunit.

Effect of Enamel Matrix Derivative Liquid on Osteoblast and Periodontal Ligament Cell Proliferation and Differentiation.

BACKGROUND Enamel matrix derivatives (EMDs) have been used clinically for more than a decade for the regeneration of periodontal tissues. The aim of the present study is to analyze the effect on cell growth of EMDs in a gel carrier in comparison to EMDs in a liquid carrier. EMDs in a liquid carrier have been shown to adsorb better to bone graft materials. METHODS Primary human osteoblasts and periodontal ligament (PDL) cells were exposed to EMDs in both gel and liquid carriers and compared for their ability to induce cell proliferation and differentiation. Alizarin red staining and real-time polymerase chain reaction for expression of genes encoding collagen 1, osteocalcin, and runt-related transcription factor 2, as well as bone morphogenetic protein 2 (BMP2), transforming growth factor (TGF)-β1, and interleukin (IL)-1β, were assessed. RESULTS EMDs in both carriers significantly increased cell proliferation of both osteoblasts and PDL cells in a similar manner. Both formulations also significantly upregulated the expression of genes encoding BMP2 and TGF-β1 as well as decreased the expression of IL-1β. EMDs in the liquid carrier further retained similar differentiation potential of both osteoblasts and PDL cells by demonstrating increased collagen and osteocalcin gene expression and significantly higher alizarin red staining. CONCLUSIONS The results from the present study indicate that the new formulation of EMDs in a liquid carrier is equally as potent as EMDs in a gel carrier in inducing osteoblast and PDL activity. Future study combining EMDs in a liquid carrier with bone grafting materials is required to further evaluate its potential for combination therapies.

An Inexpensive Alternative to CS Photoshop & Bridge: Archival Master Image Capture and Batch Derivative Creation in Canon Scan Gear & Adobe Photoshop Elements 7

This presentation was made at the Connecticut State Library Service Center, Willimantic, CT, April 14, 2009. It focused on digital capture workflows for both archival and derivative image creation using accepted current standards. Tools used were inexpensive by choice and focused towards the needs of small to mid-sized cultural heritage institutions who wish to begin digital capture in their own facilities.

GMZ27 is a new organic arsenic derivative with anti-leukemic activity, via the induction of reactive oxygen species through NADPH oxidase and mitochondrial pathway that lead to leukemia cell apoptosis

Arsenic trioxide (ATO) is an inorganic arsenic derivative that is very effective against relapsed acute promyelocytic leukemia. It is being investigated as therapy for other cancers, but the risk/benefit ratio is questionable due to significant side effects. In contrast, organic arsenic derivatives (OAD) are known to be much less toxic than ATO. Based on high activity, we selected GMZ27 (dipropil-s-glycerol arsenic) for further study and have confirmed its potent activity against human acute leukemia cell lines. This anti-leukemic activity is significantly higher than that of ATO. Both in vivo and in vitro tests have shown that GMZ27 is significantly less toxic to normal bone marrow mononuclear cells and normal mice. Therefore, further study of the biological activity of GMZ27 was undertaken. ^ GMZ27, in contrast to ATO, can only marginally induce maturation of leukemic cells. GMZ27 has no effect on cell cycle. The anti-leukemic activity of GMZ27 against acute myeolocytic leukemia cells is not dependent upon degradation of PML-RARα fusion protein. GMZ27 causes dissipation of mitochondrial transmembrane potential, cleavage of caspase 9, caspase 3 activation. Further studies indicated that GMZ27 induces intracellular reactive oxygen species (ROS) production, and modification of intracellular ROS levels had profound effect on its potential to inhibit proliferation of leukemic cells. Therefore ROS production plays a major role in the anti-leukemic activity of GMZ27. ^ To identify how GMZ27 induces ROS, our studies focused on mitochondria and NADPH oxidase. The results indicated that the source of ROS generation induced by GMZ27 is dose dependent. At the low dose (0.3 uM) GMZ27 induces NADPH oxidase activity that leads to late ROS production, while at the high dose (2.0 uM) mitochondria function is disrupted and early ROS production is induced leading to dramatic cell apoptosis. Therefore, late, ROS production can be detected in mitochondria are depleted Rho-0 cells. Our work not only delineates a major biologic pathway for the anti-leukemic activity of GMZ27, but also discusses possible ways of enhancing the effect by the co-application of NADPH oxidase activator. Further study of this interaction may lead to achieving better therapeutic index.^

Hybrid topological derivative and gradient-based methods for electrical impedance tomography

We present a technique to reconstruct the electromagnetic properties of a medium or a set of objects buried inside it from boundary measurements when applying electric currents through a set of electrodes. The electromagnetic parameters may be recovered by means of a gradient method without a priori information on the background. The shape, location and size of objects, when present, are determined by a topological derivative-based iterative procedure. The combination of both strategies allows improved reconstructions of the objects and their properties, assuming a known background.

Use of the First Derivative of Spectral Reflectance to Detect Mold on Tomatoes

The first derivative of spectral reflectance of tomatoes was studied to see whether it can detect molds and sunscald damage on the fruit. The results indicate that a quality index based on the derivative values of reflectance at 590- and 710-nm wavelengths can be used to separate good tomates from those with black mold, gray mold, and sunscald.

Damping models in the truncated derivative nonlinear Schrödinger equation

Four-dimensional flow in the phase space of three amplitudes of circularly polarized Alfven waves and one relative phase, resulting from a resonant three-wave truncation of the derivative nonlinear Schrödinger equation, has been analyzed; wave 1 is linearly unstable with growth rate , and waves 2 and 3 are stable with damping 2 and 3, respectively. The dependence of gross dynamical features on the damping model as characterized by the relation between damping and wave-vector ratios, 2 /3, k2 /k3, and the polarization of the waves, is discussed; two damping models, Landau k and resistive k2, are studied in depth. Very complex dynamics, such as multiple blue sky catastrophes and chaotic attractors arising from Feigenbaum sequences, and explosive bifurcations involving Intermittency-I chaos, are shown to be associated with the existence and loss of stability of certain fixed point P of the flow. Independently of the damping model, P may only exist as against flow contraction just requiring.In the case of right-hand RH polarization, point P may exist for all models other than Landau damping; for the resistive model, P may exist for RH polarization only if 2+3/2.

Type-I intermittency with discontinuous reinjection probability density in a truncation model of the derivative nonlinear Schrödinger equation

In previous papers, the type-I intermittent phenomenon with continuous reinjection probability density (RPD) has been extensively studied. However, in this paper type-I intermittency considering discontinuous RPD function in one-dimensional maps is analyzed. To carry out the present study the analytic approximation presented by del Río and Elaskar (Int. J. Bifurc. Chaos 20:1185-1191, 2010) and Elaskar et al. (Physica A. 390:2759-2768, 2011) is extended to consider discontinuous RPD functions. The results of this analysis show that the characteristic relation only depends on the position of the lower bound of reinjection (LBR), therefore for the LBR below the tangent point the relation {Mathematical expression}, where {Mathematical expression} is the control parameter, remains robust regardless the form of the RPD, although the average of the laminar phases {Mathematical expression} can change. Finally, the study of discontinuous RPD for type-I intermittency which occurs in a three-wave truncation model for the derivative nonlinear Schrodinger equation is presented. In all tests the theoretical results properly verify the numerical data

A Compact Formula for the Derivative of a 3-D Rotation in Exponential Coordinates

We present a compact formula for the derivative of a 3-D rotation matrix with respect to its exponential coordinates. A geometric interpretation of the resulting expression is provided, as well as its agreement with other less-compact but better-known formulas. To the best of our knowledge, this simpler formula does not appear anywhere in the literature. We hope by providing this more compact expression to alleviate the common pressure to reluctantly resort to alternative representations in various computational applications simply as a means to avoid the complexity of differential analysis in exponential coordinates.

A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window

The only treatment of patients with acute ischemic stroke is thrombolytic therapy, which benefits only a fraction of stroke patients. Both human and experimental studies indicate that ischemic stroke involves secondary inflammation that significantly contributes to the outcome after ischemic insult. Minocycline is a semisynthetic second-generation tetracycline that exerts antiinflammatory effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against focal brain ischemia with a wide therapeutic window. Using a rat model of transient middle cerebral artery occlusion, we show that daily treatment with minocycline reduces cortical infarction volume by 76 ± 22% when the treatment is started 12 h before ischemia and by 63 ± 35% when started even 4 h after the onset of ischemia. The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1β-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E2 production. Minocycline had no effect on astrogliosis or spreading depression, a wave of ionic transients thought to contribute to enlargement of cortical infarction. Treatment with minocycline may act directly on brain cells, because cultured primary neurons were also salvaged from glutamate toxicity. Minocycline may represent a prototype of an antiinflammatory compound that provides protection against ischemic stroke and has a clinically relevant therapeutic window.

An NO derivative of ursodeoxycholic acid protects against Fas-mediated liver injury by inhibiting caspase activity

Caspases are key mediators in liver inflammation and apoptosis. In the present study we provide evidence that a nitric oxide (NO) derivative of ursodeoxycholic acid (UDCA), NCX-1000 ([2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester]), protects against liver damage in murine models of autoimmune hepatitis induced by i.v. injection of Con A or a Fas agonistic antibody, Jo2. Con A administration causes CD4+ T lymphocytes to accumulate in the liver and up-regulates FasL expression, resulting in FasL-mediated cytotoxicity. Cotreating mice with NCX-1000, but not with UDCA, protected against liver damage induced by Con A and Jo2, inhibited IL-1β, IL-18, and IFN-γ release and caspase 3, 8, and 9 activation. Studies on HepG2 cells demonstrated that NCX-1000, but not UDCA, directly prevented multiple caspase activation induced by Jo2. Incubating HepG2 cells with NCX-1000 resulted in intracellular NO formation and a DTT-reversible inhibition of proapoptotic caspases, suggesting that cysteine S-nitrosylation was the main mechanism responsible for caspase inhibition. Collectively, these data suggest that NCX-1000 protects against T helper 1-mediated liver injury by inhibiting both the proapoptotic and the proinflammatory branches of the caspase superfamily.