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PubMed2006

The antithrombotic and anti-inflammatory effects of BCX-3607, a small molecule tissue factor/factor VIIa inhibitor.

Tissue factor (TF) is a transmembrane glycoprotein that binds its zymogen cofactor, Factor VIIa (FVIIa) on the cell surface. Together (TF/FVIIa) they activate Factor X (FX) and Factor IX (FIX) and start the extrinsic pathway of blood coagulation. As such, the TF/FVIIa complex plays an important role in normal physiology as well as in thrombotic diseases such as unstable angina (UA), disseminated intravascular coagulation (DIC), and deep vein thrombosis (DVT). In addition to its function as an initiator of coagulation, TF/FVIIa plays an important role in inflammation. Expression of TF on the cell surface and its appearance as a soluble molecule are characteristic features of acute and chronic inflammation in conditions such as sepsis and atherosclerosis. Here we demonstrate that BCX-3607, a small molecule potent inhibitor of TF/FVIIa, reduces thrombus weight in an animal model of DVT. BCX-3607 also decreases the level of interleukin-6 (IL-6) in a LPS-stimulated mouse model of endotoxemia. Additionally, in vitro studies indicate that BCX-3607 blocks the generation of TF/FVIIa-induced IL-8 mRNA in human keratinocytes and reduces the TF/FVIIa-mediated generation of IL-6 and IL-8 in human umbilical vein endothelial cells (HUVEC). Therefore, BCX-3607 might block the TF/FVIIa-mediated coagulation and inflammation associated with pathological conditions.

Animals↗

PubMed1997

Reaction of Nitrogen Chelates with the [Rh(2)](4+) Core: Bis-Chelate Products and Demonstration of Reversible, Chelate-Based Reduction Processes.

The preparations and properties are described of a series of [Rh(2)](4+) complexes possessing carboxylates and N-based chelates as ligands. Treatment of Rh(2)(O(2)CR)(4)(MeOH)(2) (R = Me (1), Et (2), Ph (3) or CF(3) (4)) with 2 equiv of 2,2'-bipyridine (bpy) in refluxing MeCN leads to the [Rh(2)(O(2)CR)(2)(bpy)(2)](2+) cation (in complexes 5-9). Reaction of 1 with 1,10-phenanthroline (phen), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bpy), 4,4'-diphenyl-2,2'-bipyridine (Ph(2)bpy), and 4,7-diphenyl-1,10-phenanthroline (Ph(2)phen) leads to the analogous cations of complexes 10-13. Complex 6a, [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](PF(6))(2).2MeCN, crystallizes in monoclinic space group P2(1)/a with the following cell parameters at -172 degrees C: a = 14.433(2) Å, b = 12.810(1) Å, c = 22.78(3) Å, beta = 104.42(3) degrees, Z = 4, and V = 3971.2 Å(3). Complex 9, [Rh(2)(O(2)CCF(3))(4)(bpy)(2)].Me(2)CO, crystallizes in triclinic space group P&onemacr; with the following cell parameters at 20 degrees C: a = 14.260(4) Å, b = 15.375(4) Å, c = 9.709(2) Å, alpha = 105.98(2) degrees, beta = 97.49(2) degrees, gamma = 70.32(2) degrees, Z = 2, and V = 1925.2 Å(3). Both 6a and 9 contain a singly-bonded [Rh(2)](4+) unit with two cis bridging RCO(2)(-) groups and two syn-bpy chelate groups in a near-eclipsed conformation about the Rh-Rh vector. Reaction of [Rh(2)(tpy)(2)(MeCN)(4)](BF(4))(4) (15) (tpy = 2,2':6',2"-terpyridine) with NBu(n)(4)(O(2)CPh) gives [Rh(2)(O(2)CPh)(tpy)(2)(MeCN)(2)](BF(4))(3).MeCN (16). Complex 16 crystallizes in triclinic space group P&onemacr; with the following cell parameters at -168 degrees C: a = 11.684(4) Å, b = 20.373(8) Å, c = 10.451(3) Å, alpha = 93.47(2) degrees, beta = 110.53(1) degrees, gamma = 100.03(2) degrees, Z = 2, and V = 2274.1 Å(3). The cation of 16 consists of a [Rh(2)](4+) unit with a bridging PhCO(2)(-) group and two chelating tpy groups. The solution (1)H NMR properties of complexes 6-13 and 16 show the complexes to retain their solid-state structures on dissolution. The electrochemical properties of 6-13 and 16 were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in MeCN. The bis(bpy) and -(phen) complexes 6-8, 10, and 11 show a reversible, one-electron reduction in the range -0.83 to -0.91 V vs ferrocene and an additional, irreversible reduction and an irreversible oxidation; the Ph(2)bpy (12) and Ph(2)phen (13) complexes show a two-electron reversible reduction at -0.61 to -0.76 and a reversible one-electron oxidation at 0.68-0.89 V. Consideration of the potentials as a function of carboxylate and chelate identity leads to the conclusion that the reductions are ligand (chelate)-based. This is supported by an extended Hückel calculation on the model compound [Rh(2)(O(2)CH)(2)(bpy)(2)(HCN)(2)](2+), which shows the LUMO to be a bpy-based orbital comprising in-phase, sigma overlap of two bpy pi orbitals, one on each of the syn-bpy groups. In contrast, complex 16 shows no reversible reduction processes. Complex 6b, [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](BF(4))(2), in MeCN may be reduced with sodium acenaphthylenide in THF to give deep blue [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](BF(4)) (14) in high yield. The cation of 14 may also be generated by controlled potential electrolysis of 6a in MeCN at -0.99 V and by heating of a solution of 6a or 6b in alcohol.

Journal Article↗

PubMed2005

CAP and arousals are involved in the homeostatic and ultradian sleep processes.

There is growing evidence that cyclic alternating pattern (CAP) and arousals are woven into the basic mechanisms of sleep regulation. In the present study, the overnight sleep cycles (SC) of 20 normal subjects were analyzed according to their stage composition, CAP rate, phase A subtypes and arousals. Individual SC were then divided into 10 normalized temporal epochs. CAP parameters and arousals were measured in each epoch and averaged in relation to the SC order. Subtypes A2 and A3 of CAP in non-rapid eye movement (NREM) sleep, and arousals, both in REM and NREM sleep when not coincident with a A2 or A3 phases, were lumped together as fast electroencephalographic (EEG) activities (FA). Subtypes A1 of CAP, characterized by slow EEG activities (SA), were analyzed separately. The time distribution of SA and FA was compared to the mathematical model of normal sleep structure including functions representing the homeostatic process S, the circadian process C, the ultradian process generating NREM/REM cycles and the slow wave activity (SWA) resulting from the interaction between homeostatic and ultradian processes. The relationship between SA and FA and the sleep-model components was evaluated by multiple regression analysis in which SA and FA were considered as dependent variables while the covariates were the process S, process C, SWA, REM-on and REM-off activities and their squared values. Regression was highly significant (P < 0.0001) for both SA and FA. SA were prevalent in the first three SC, and exhibited single or multiple peaks immediately before and in the final part of deep sleep (stages 3 + 4). The peaks of FA were delayed and prevailed during the pre-REM periods of light sleep (stages 1 + 2) and during REM sleep. SA showed an exponential decline across the successive SC, according to the homeostatic process. In contrast, the distribution of FA was not influenced by the order of SC, with periodic peaks of FA occurring before the onset of REM sleep, in accordance with the REM-on switch. The dynamics of CAP and arousals during sleep can be viewed as an intermediate level between cellular activities and macroscale EEG phenomena as they reflect the decay of the homeostatic process and the interaction between REM-off and REM-on mechanisms while are slightly influenced by circadian rhythm.

Activity Cycles↗

PubMed2003

Haplotyping as perfect phylogeny: a direct approach.

A full haplotype map of the human genome will prove extremely valuable as it will be used in large-scale screens of populations to associate specific haplotypes with specific complex genetic-influenced diseases. A haplotype map project has been announced by NIH. The biological key to that project is the surprising fact that some human genomic DNA can be partitioned into long blocks where genetic recombination has been rare, leading to strikingly fewer distinct haplotypes in the population than previously expected (Helmuth, 2001; Daly et al., 2001; Stephens et al., 2001; Friss et al., 2001). In this paper we explore the algorithmic implications of the no-recombination in long blocks observation, for the problem of inferring haplotypes in populations. This assumption, together with the standard population-genetic assumption of infinite sites, motivates a model of haplotype evolution where the haplotypes in a population are assumed to evolve along a coalescent, which as a rooted tree is a perfect phylogeny. We consider the following algorithmic problem, called the perfect phylogeny haplotyping problem (PPH), which was introduced by Gusfield (2002) - given n genotypes of length m each, does there exist a set of at most 2n haplotypes such that each genotype is generated by a pair of haplotypes from this set, and such that this set can be derived on a perfect phylogeny? The approach taken by Gusfield (2002) to solve this problem reduces it to established, deep results and algorithms from matroid and graph theory. Although that reduction is quite simple and the resulting algorithm nearly optimal in speed, taken as a whole that approach is quite involved, and in particular, challenging to program. Moreover, anyone wishing to fully establish, by reading existing literature, the correctness of the entire algorithm would need to read several deep and difficult papers in graph and matroid theory. However, as stated by Gusfield (2002), many simplifications are possible and the list of "future work" in Gusfield (2002) began with the task of developing a simpler, more direct, yet still efficient algorithm. This paper accomplishes that goal, for both the rooted and unrooted PPH problems. It establishes a simple, easy-to-program, O(nm(2))-time algorithm that determines whether there is a PPH solution for input genotypes and produces a linear-space data structure to represent all of the solutions. The approach allows complete, self-contained proofs. In addition to algorithmic simplicity, the approach here makes the representation of all solutions more intuitive than in Gusfield (2002), and solves another goal from that paper, namely, to prove a nontrivial upper bound on the number of PPH solutions, showing that that number is vastly smaller than the number of haplotype solutions (each solution being a set of n pairs of haplotypes that can generate the genotypes) when the perfect phylogeny requirement is not imposed.

Algorithms↗

PubMed2026

Fast, accurate construction of multiple sequence alignments from protein language embeddings.

Multiple sequence alignment (MSA) is a foundational task in computational biology, underpinning protein structure prediction, evolutionary analysis, and domain annotation. Traditional MSA algorithms rely on pairwise amino acid substitution matrices derived from conserved protein families. While effective for aligning closely related sequences, these scoring schemes struggle in the low-identity "twilight zone." Here, we present a new approach for constructing MSAs leveraging amino acid embeddings generated by protein language models (PLMs), which capture rich evolutionary and contextual information from massive and diverse sequence datasets. We introduce a windowed reciprocal-weighted embedding similarity metric that is surprisingly effective in identifying corresponding amino acids across sequences. Building on this metric, we develop ARIES (Alignment via RecIprocal Embedding Similarity), an algorithm that constructs a PLM-generated template embedding and aligns each sequence to this template via dynamic time warping in order to build a global MSA. Across diverse benchmark datasets, ARIES achieves higher accuracies than existing state-of-the-art approaches, especially in low-identity regimes where traditional methods degrade, while scaling almost linearly with the number of sequences to be aligned. Together, these results provide the first large-scale demonstration of the power of PLMs for accurate and scalable MSA construction across protein families of varying sizes and levels of similarity, highlighting the potential of PLMs to transform comparative sequence analysis.

Deep Learning↗

PubMed2025

CASTER-DTA: Equivariant Graph Neural Networks for Predicting Drug-Target Affinity.

Accurately determining the binding affinity of a ligand with a protein is important for drug design, development, and screening. With the advent of accessible protein structure prediction methods such as AlphaFold, predicted protein 3D structures are readily available; however, methods for predicting binding affinity currently do not take full advantage of 3D protein information. Here, we present CASTER-DTA (Cross-Attention with Structural Target Equivariant Representations for Drug-Target Affinity), which uses an equivariant graph neural network to learn more robust protein representations alongside a standard graph neural network to learn molecular representations to predict drug-target affinity. We augment these representations by incorporating an attention-based mechanism between protein residues and drug atoms to improve interpretability. We show that CASTER-DTA represents a state-of-the-art improvement on multiple benchmarks for predicting drug-target affinity and that it generates novel insights for several related tasks. We then apply CASTER-DTA to create a large resource of the binding affinities of every FDA-approved drug against every protein in the human proteome and make these predictions freely available for download. We also make available a web server for researchers to apply a pretrained CASTER-DTA model for predicting binding affinities between arbitrary proteins and drugs.

deep learning↗

PubMed2005

Grain morphology and trapping effects on electron transport in dye-sensitized nanocrystalline solar cells.

We have examined the combined effects of grain morphology and electron trapping on the transient response of photoelectrons moving through the TiO2 grains in a dye-sensitized nanocrystalline solar cell using a multi-time-scale random walk Monte Carlo model. Our use of a multi-time-scale approach enables us to simulate transport for electrons moving through spherical connected grains in a three-dimensional (3D) voided network and look at the effect of the size of interparticle boundaries on carrier dynamics. We can also address similar times to those over which measurements are taken, namely, 0.1 ms. These times are long because of deep traps in the TiO2 grains. The grains have 2-fold connectivity in one dimension (linear chains) or 4-fold or 6-fold connectivity in three dimensions and traps with an exponential distribution of energies. Photoelectrons are generated by a light pulse of short duration. The spatial distribution of the photogenerated electron density from this pulse either has a uniform profile or is peaked on the electrolyte side. We show that the constrictions at the grain necks slow the electrons, making trapping more likely and hence further delaying their passage to the extracting electrode. By comparing our results for 4-fold and 6-fold coordinated particles on a cubic lattice with 2-fold coordinated particles on linear chains, we show that transport is slowed in the former case due to the additional paths available to the electrons in the 3D network. We also find that the charge and current transients cannot be fit to an analytical solution of the continuum equations with an effective diffusion coefficient even at long times. Therefore, caution must be exercised when attempting to fit experimental transient data with an effective diffusion coefficient.

Journal Article↗

PubMed2002

The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: a model for the secondary evolution of the classic C2h dimer and comparison of four mechanisms.

A mechanism is proposed for the formation in gas phase, during a short time, of the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry structures most likely to be formed in the supersonic jet expansion molecular beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown to be capable of unhinging about the hydrogen-bond pair as an axis, from 0 degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h) structure with its delicate geometry and symmetry. This relaxation mechanism is feasible in the 3-micros interval between the nozzle escape and the first laser pulse interception of the molecular beam. In the second part of the paper four published mechanisms are compared for concerted vs. two-step biprotonic phototransfer for the 7AI dimers. The dependence of the latter two models on H-atom instead of proton-transfer as an intermediate step negates the mechanism in a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron orbital that would be generated. The concerted mechanism for biprotonic phototransfer is reaffirmed by the analysis of the quantum mechanical conditions set on the biprotonic transfer in the photo-excited molecular 7AI pair.

Dimerization↗

PubMed1980

Heating patterns produced by 434 MHz erbotherm UHF 69.

Thermal distributions of 434 MHz Erbotherm H 69 hyperthermia/diathermy generators in tissue-equivalent medium have been investigated. Thermocouples were used to measure temperatures at a set of grid points. Cylindrical and abdominal phantoms were heated and sectioned after heating to measure the temperatures at depth. Results indicate that there is potential for heating deep-seated tumors. The distributions were influenced by the number, shape and geometry of the applicators employed.

Diathermy↗

PubMed1997

The vanishing defibrillator syndrome: incidence, mechanism, and clinical relevance.

Intraperitoneal migration of an abdominally implanted cardioverter defibrillator is a complication not yet fully described. In a consecutive series of 195 patients, migration occurred between 1 and 20 months in 5 (8%) of the 63 patients in whom a subrectus abdomini placement of the generator was chosen. It was unrelated to the patients' clinical characteristics or the defibrillator model. Dysuria and inability to interrogate the device were present in every subject, and the diagnosis was confirmed by the characteristic abdominal x-ray appearance and the findings at the time of surgery. Adhesions involving the omentum, and in one case, the small bowels, were present in three patients and seem to be related to the length of intraabdominal permanence of the generator. Because this complication may be due to specific anatomical characteristics of the aponeurosis of the abdominal muscles, it is likely that its incidence will be unchanged by the use of smaller devices. A close follow-up of the generators implanted deep to the rectus fascia is therefore advisable.

Abdomen↗

PubMed1998

Pain processing traced by magnetoencephalography in the human brain.

The temporal and spatial processing of pain perception in human was traced by magnetoencephalography (MEG). We applied a painful CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated areas using a single equivalent current dipole (ECD) at each time point, and a brain electric source analysis (BESA) as a spatio-temporal multiple source analysis method. The four-source model was found to be the most appropriate; sources 1 and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the stimulation, respectively. Activities in all 4 areas were temporally overlapped. Activity in the primary sensory cortex (SI) contralateral to the stimulated site was not identified. Activity in the cingulate cortex was also not clearly identified. These results are probably due to one or more of the following factors; (1) the cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres interfere with each other. No significant or consistent magnetic fields were recorded after 500 msec following the stimulation, probably due to the complicated spatial and temporal overlapping of activities in multiple areas.

Adult↗

PubMedDate not supplied

Fluconazole therapy for experimental cryptococcosis and candidiasis in the rabbit.

Fluconazole is a second-generation azole compound with broad-spectrum antifungal activity. It has been examined in several animal models emphasizing important clinical sites of infection with common yeast pathogens. The drug has an excellent pharmacokinetic profile for central nervous system, renal, and ocular infections; at these sites fluconazole has been successful in the treatment of infections with Cryptococcus neoformans or Candida albicans. On the basis of the experience in animals, fluconazole should be critically evaluated in the treatment of human mycoses such as cryptococcosis of the central nervous system and renal/ocular candidiasis. This agent represents the new wave of interest in the increasingly troublesome problem of deep-seated fungal infections.

Animals↗

PubMedDate not supplied

Neuroprotection and neurodegenerative diseases: from biology to clinical practice.

Neurodegenerative diseases and, in particular, Alzheimer disease, are characterized by progressive neuronal loss correlated in time with the symptoms of the disease considered. Whereas the symptoms of those incapacitating diseases are beginning to be managed with a relative efficacy, the ultimate objective of therapy nonetheless remains preventing cell (neuronal and/or astrocytic) death in a neurocytoprotective approach. In biologic terms, in the light of progress at basic research level, three strategies may be envisaged: (1) antagonizing the cytotoxic causal events (excess intracellular calcium, accumulation of abnormal proteins, excitotoxic effects of amino acids, oxidative stress, processes related to inflammation, etc.); (2) stimulating the endogenous protective processes (anti-free radical or DNA repair systems, production of neurotrophic factors, potential cytoprotective action of steroids, etc.); (3) promoting damaged structure repair strategies (grafts) or deep brain or cortical neurostimulation with a view to triggering (beyond the symptomatic actions) potential 'protective' cell mechanisms. The clinical transition of the various strategies whose efficacy is being tested in animal and/or cell models, experimental analogs of the diseases, and thus the objective demonstration in humans of pharmacological and/or surgical neurocytoprotection, is currently the subject of considerable methodological debate (What are the right psychometric assessment criteria? What are the most pertinent laboratory or neuroradiological markers, etc.?). A number of clinical trials have been completed or are ongoing with drugs that are reputed to be neuroprotective. Thus, elements of the response are beginning to be generated with a view to determining whether it will soon be possible to effectively slow or even stop the neurodegenerative process whose etiology, in most cases, remains obscure.

Alzheimer Disease↗

PubMed2025

Decoding the Functional Interactome of Non-Model Organisms with PHILHARMONIC.

Despite the widespread availability of genome sequencing pipelines, many genes remain part of the genome's "dark matter," where existing inference tools cannot even begin to guess the biological function of their proteins from sequence alone. This challenge is especially pronounced in organisms that are highly evolutionarily distant from well-studied models, where homology-based methods break down. Here, we describe PHILHARMONIC, a computational method that combines deep learning-based de novo protein interaction network inference with robust unsupervised spectral clustering and remote homology to illuminate functional organization in any non-model organism. From only a sequenced proteome, we show PHILHARMONIC predicts protein functions, functional communities, and higher-order network structure with high accuracy. We validate its performance using experimental gene expression and pathway data in D. melanogaster, and we demonstrate its broad utility by analyzing temperature sensing and stress response pathways in the reef-building coral P. damicornis and its algal symbiont C. goreaui. PHILHARMONIC provides a general-purpose engine for functional discovery and biological hypothesis generation in non-model organisms, enabling systems-level insights across the full diversity of life.

Journal Article↗

PubMed1997

Volumetric transformation of brain anatomy.

This paper presents diffeomorphic transformations of three-dimensional (3-D) anatomical image data of the macaque occipital lobe and whole brain cryosection imagery and of deep brain structures in human brains as imaged via magnetic resonance imagery. These transformations are generated in a hierarchical manner, accommodating both global and local anatomical detail. The initial low-dimensional registration is accomplished by constraining the transformation to be in a low-dimensional basis. The basis is defined by the Green's function of the elasticity operator placed at predefined locations in the anatomy and the eigenfunctions of the elasticity operator. The high-dimensional large deformations are vector fields generated via the mismatch between the template and target-image volumes constrained to be the solution of a Navier-Stokes fluid model. As part of this procedure, the Jacobian of the transformation is tracked, insuring the generation of diffeomorphisms. It is shown that transformations constrained by quadratic regularization methods such as the Laplacian, biharmonic, and linear elasticity models, do not ensure that the transformation maintains topology and, therefore, must only be used for coarse global registration.

Animals↗

PubMed2001

Chimaeras and mosaics for dissecting complex mutant phenotypes.

Back at the first half of the 1980s, there was no mammalian experimental embryology in Hungary. One of us, AN, took up the challenge of establishing a small group in the field. In the absence of local information, AN and his former colleague, Andras Paldi (AP), used their tourist passport to visit several laboratories in Western Europe and collect information and advice. This is how AN and AP ended up one day sitting in Anne McLaren's office in the MRC Mammalian Development Unit at University College, London. They never forgot her endless enthusiasm and the way she clearly explained the important points of preimplantation embryo manipulation, chimaera making and embryo transfer. As well as the extremely useful suggestions, which were crucial to starting the lab in Hungary, they also took back her deep love for embryo development. They remember her telling them, 'never waste an embryo--there is always another unanswered question it can solve'. Many who have been lucky and experienced Anne's spirit and advice later realized how useful it was to generate 'new' ideas by following the 'not wasting' principle. Our views on chimaeras presented below definitely contain elements which grew out from this principle.

Animals↗

PubMedDate not supplied

[An experimental model of the vertical transmission of the Coxsackie-group enteroviruses and its use in developing methods to prevent congenital coxsackievirus infection].

An experimental model of vertical transmission of Coxsackie group enteroviruses was developed in BALB/c mice the first generation of which was infected with Coxsackie A18 virus in the neonatal period. Persistence of the virus was demonstrated in all females of the first generation tested and in 90.9% to 100% of the animals of the next two generations. Cytochemical analysis of the enzyme status of lymphocytes revealed reliable relationship between the depression of energetic metabolism enzymes and the activity of virus amplification in the animals under study. The correction of aerobic respiration in pregnant females by administration of a complex of energy metabolism substrates and cofactors was accompanied by a significant reduction of the virus infection activity in the females and their offsprings as well as by prevention of transplacental infection in some litters. The experimental model of vertical transmission of enteroviruses is proposed for use in the development of methods for prevention of congenital Coxsackie virus infection. The authors express their deep gratitude to the sponsor of the publication--NOVRUZ Co., Turkmenistan.

Animals↗

PubMedDate not supplied

Influence of different factors on bond strength of hybrid ionomers.

A new generation of filling materials, the hybrid-ionomer cements, has been introduced recently. In many clinical situations these hybrid ionomers may be an alternative to conventional glass-ionomer cements and resins bonded with dentin bonding agents. During the past years research has focused on factors influencing bond strength of dentin bonding systems, but there is not much knowledge about the bond strength of hybrid- and glass-ionomer filling materials under different conditions. Bond strengths of four hybrid ionomers, one conventional glass-ionomer cement, and one cermet cement were determined in superficial and deep, dry and moist dentin using a simplified pulp chamber model. All materials showed significantly higher bond strength to superficial compared to deep dentin. Moisture showed no significant influence on any material neither in deep nor in superficial dentin. Bond strengths of Fuji II LC, Variglass, and Vitremer were distinctly higher than those of the conventional glass-ionomer cement (Ketac-Fil) and the cermet cement (Ketac-Silver), while that of Photac-Fil was not significantly different. Ionomer samples failed cohesively in superficial dentin in over 60% of the samples. The bonding interfaces between Fuji II LC and Variglass and the treated dentin surface showed tags but no distinct hybrid layer. Bond strength is not only dependent on the pretreatment of the dentin, but also on the glass-ionomer resin composition of the material.

Acrylic Resins↗