bluuebunny/crossref_metadata_2025 huggingface dataset:
Smokeless Tobacco: an Addicting Drug
Authors: Henningfield J.E. , Fant R.V. , Tomar S.L.
Published: January 2009

In 1986, the Surgeon General concluded that smokeless tobacco is an addictive drug sharing many qualities with other drugs of abuse such as morphine and cocaine. Smokeless tobacco can be used to deliver psycho-active and dependence-producing levels of nicotine. Tolerance develops with repeated use, causing the user to increase nicotine dosing through increased use and/or switching to products with higher nicotine yields. Clinical signs of nicotine withdrawal develop upon cessation of use. Recent data show that smokeless tobacco products vary widely in their nicotine dosing capabilities. Low-dose products tend to be those commonly marketed toward, and used by, young people without previous smokeless tobacco experience. Many of these people develop dependence and switch to high-dose products. The present article discusses each of these qualities of smokeless tobacco in greater detail. The article also discusses qualities of smokeless tobacco that make it an effective nicotine delivery device that leads to addiction.
Systemic Absorption and Effects of Nicotine From Smokeless Tobacco
Authors: Benowitz N.L.
Published: January 2009

Nicotine is absorbed in substantial quantities from smokeless tobacco and could contribute to the adverse consequences of smokeless tobacco use. Chronic systemic exposure to nicotine could contribute to accelerated coronary artery disease, acute cardiac ischemic events, and hypertension. Systemic absorption of sodium and mutagenic chemicals from smokeless tobacco could aggravate hypertension or cardiac failure, or contribute to cancer, respectively. Information concerning the potential hazards of nicotine and other systemically absorbed toxins may be incorporated into educational programs to discourage the use of smokeless tobacco.
X-Ray-Induced Photoelectron Spectroscopy of Dentin as a Function of Duration of Ar +-Ion Etching
Authors: Ten Bosch J.J. , De Vries J. , Van Der Veen M.H.
Published: January 2009

XPS, or ESCA, measures the atomic concentration in the outermost layers of the sample. The surface is often etched with Ar+-ions before any measurement. We investigated the role thereof on XPS measurements of root dentin. Nine slices were cut from premolars. Slices were ground or broken. XPS was measured before etching. Six samples were then subjected to Ar+-ion etching (10 kV ions, 0.25 μA/mm2). A gold sample was also included. Relative concentrations of N and C decreased with etching time, while 0, P, and Ca increased. N and C curves were analyzed assuming a sum of two exponential decays and a final level. On average, τ1 = 20 sec for C and 17 sec for N. On average, τ2 = 278 sec for C and 350 sec for N. No differences between differently prepared samples were apparent. The gold sample showed a single decay to noise for C and N, with τ1 = 8 and 7 sec, respectively. We conclude that two decay processes are present, due to gas removal and to the removal of organic material from the dentin matrix, respectively. Thus, true values can be obtained by extrapolation to t = 0 of only the data obtained by summing the slow decay and the final level.
Fact and Artefact in Confocal Microscopy
Authors: Watson T.F.
Published: January 2009

High-resolution confocal microscopic images may be made of either the surface of a sample or beneath the surface. These images can be likened to optical tomograms, giving thin (> 0.35 μm) slices up to 200 μm below the surface of a transparent tissue: With microscopes running under normal conditions, the optical section thickness will be >1 μm and the effective penetration into enamel and dentin a maximum of 100 μm. For maximum resolution, high-quality, high-numerical-aperture objectives should be used. Refractive index matching of the lens immersion media and the substrate will avoid distortions of images in the optical axis. Such errors could occur when imaging a considerable distance (> 40 μm) into a cell containing water, with an oil immersion objective above the cover slip. Care should be taken in the interpretation of computerized z axis reconstructions made from serial optical sections: Their validity should be checked with equivalent views made with the sample oriented in the same direction as the reconstruction. The use of fluorescent dyes in microscopy is a very powerful investigative technique. It is important that the dyes used not be labile and that they be well-fixed to the materials being examined, or the images may indicate the dye distribution rather than the material to which it is "attached". Multiple labeling experiments must have crossover control experiments to verify the distribution of the individual dyes. Valuable information can often be gained by combining information from both reflection and fluorescence images. Two-photon laser excitation of dyes gives the potential for greater depth penetration and improved resolution.
The Caries-Preventive Effect of Titanium Tetrafluoride on Root Surfaces in Situ as Evaluated by Microradiography and Confocal Laser Scanning Microscopy
Authors: Büyükyilmaz T. , Øgaard B. , Duschner H. , Ruben J. , Arends J.
Published: January 2009

The aim of the present study was to investigate the cariostatic effect of titanium tetrafluoride (TiF4) on in situ-induced lesions on human root surfaces. Analysis of the samples was carried out by quantitative microradiography (TMR) and confocal laser scanning microscopy (CLSM). Pre-molar roots, sectioned into four pieces, were used for sample preparation. Before they were mounted into the recesses prepared in the acrylic intra-oral appliances, two root pieces from each tooth were treated with 4% TiF4 for 1 min, while the remaining two pieces served as controls. The appliances were worn by 12 volunteers for 4 wks. After 4 wks with no fluoride supplementation, the root pieces were removed and analyzed by TMR and CLSM. The TMR results showed that the TiF4 treatment reduced lesion depth and total mineral loss by 56% and 62%, respectively. CLSM images agreed well with the TMR measurements. A dense light-reflecting surface layer with almost intact subsurface structures was evident in the TiF4-treated samples.
Analysis of a General Principle of Crystal Nucleation, Formation in the Different Hard Tissues
Authors: Höhling H.J. , Arnold S. , Plate U. , Stratmann U. , Wiesmann H.P.
Published: January 2009

We have found, at high EM magnification, on ultrathin sections of shock-frozen, freeze-dried, embedded pieces of the developing hard tissues, that the primary crystallites consist of strands composed of nanometer-sized apatitic islands, which rapidly coalesce to needles and afterward to platelets. By small-area electron diffraction, with energy-filtered electrons, it was clarified that these strands are already crystallographically oriented along the bipolar c-axis so that the center-to-center distances between the islands would reflect the distances between crystal-nucleating sites along the matrix. The EM analysis of the cross-cut stained unmineralized and of the unstained mineralized collagen fibers of turkey tibia tendon shows that the staining "nuclei" and the early crystallites, appearing as dark dots, surround "light" round structures, which we interpret as the collagen microfibrils, surrounded by the apatitic crystallites.
Quantitative Determination of Type A and Type B Carbonate in Human Deciduous and Permanent Enamel by Means of Fourier Transform Infrared Spectrometry
Authors: Sønju Clasen A.B. , Ruyter I.E.
Published: January 2009

Caries progression has been shown to be faster in the deciduous than in the permanent dentition. Several factors influence caries progression. Among these are variations in the chemical composition of the two enamel types. The carbonate ion is known to occupy two different positions in the hydroxyapatite structure of the enamel, the hydroxide position (A) and the phosphate position (B). Carbonate may be of different chemical importance in the two lattice positions. In the present study, a quantitative determination of the carbonate in the two different positions (type A and type B) in deciduous and permanent enamel was performed by FTIR spectrometry. Calibration curves, made with synthesized hydroxyapatites with carbonates in either position, were used to determine the quantity of type A and type B carbonates in both enamel types. The deciduous enamel contained significantly more type A carbonate than permanent enamel. The total carbonate content (sum of type A and type B carbonates) was also significantly higher in deciduous than in permanent enamel. TG analysis of enamel samples confirmed the quantitative carbonate determinations by FTIR spectrometry. The difference in carbonate content between deciduous and permanent enamel may be one of several factors contributing to faster caries progression in deciduous teeth.
Zeta Potentials of Human Enamel and Hydroxyapatite as Measured by the Coulter® DELSA 440
Authors: Young A. , Smistad G. , Karlsen J. , Rölla G. , Rykke M.
Published: January 2009

The zeta potential of human enamel is of physiological importance for interactions between enamel surfaces and the surrounding aqueous medium of saliva. The zeta potentials of both enamel and hydroxyapatite (HA) have been examined previously by various techniques. In this study, we examined the zeta potential of human enamel and HA using the Coulter® DELSA 440, which, by a laser, makes independent Doppler shift measurements of moving particles in an electric field at 4 different angles, providing advantages over previous techniques. The enamel and HA particles were suspended directly in different phosphate buffers, or first incubated for 2 hrs in parotid (PS) or whole saliva (HWS) and then suspended in the same buffers. The enamel and HA particles exhibited an overall net surface potential of -15 to -30 mV, depending on the buffer content. Incubation in PS and HWS gave less negative potentials of -8 to -14 mV. In our previous studies, the salivary micelle-like structures (SMSs), seen in TEM of parotid saliva, were observed to have a zeta potential of -9 mV (Rykke et al., 1996). The zeta potential determinations in this study support the concept of an adsorption of mostly SMSs to the enamel surfaces, with a change of the zeta potential of the enamel and HA toward that of the SMSs.
Cleaning Power and Abrasivity of European Toothpastes
Authors: Wiilknitz P.
Published: January 2009

For 41 toothpastes available to European consumers in 1995, the cleaning efficacy was evaluated in comparison with abrasivity on dentin (RDA value). For cleaning power assessment, a modified pellicle cleaning ratio (PCR) measurement method was developed. The method is characterized by a five-day tea-staining procedure on bovine front teeth slabs on a rotating wheel, standardized brushing of the slabs in a V8 cross-brushing machine, and brightness measurement by a chromametric technique. All tested products were in accordance with the new DIN/ISO standard 11609 for toothpastes in terms of dentin abrasivity. Not a single product exceeded an RDA value of 200. The majority of toothpastes (80%) had an RDA value below 100. Only three products surpassed the reference in cleaning power. Most products (73%) had a cleaning power (PCR value) between 20 and 80. The correlation between cleaning power and dentin abrasion was low (r = 0.66), which can be explained with the different influence on dentin and stains by factors like abrasive type, particle surface and size, as well as the chemical influence of other toothpaste ingredients. Some major trends could be shown on the basis of abrasive types. The ratio PCR to RDA was rather good in most silica-based toothpastes. A lower ratio was found in some products containing calcium carbonate or aluminum trihydrate as the only abrasive. The addition of other abrasives, such as polishing alumina, showed improved cleaning power. Some active ingredients, especially sequestrants such as sodium tripolyphosphate or AHBP, also improve the PCR/ RDA ratio by stain-dissolving action without being abrasive. The data for some special anti-stain products did not differ significantly from standard products. Compared with data measured in 1988, a general trend toward reduced abrasivity without loss of cleaning efficacy could be noticed on the European toothpaste market. This may be mostly due to the increased use of high-performance abrasives such as hydrated silica.
Effects of Tetracyclines on the Pathologic Activity of Endotoxin: in Vitro and in Vivo Studies
Authors: Shapira L. , Barak V. , Soskolne W.A. , Halabi A. , Stabholz A.
Published: January 2009

Lipopolysaccharide (LPS) is considered to be one of the major virulence factors of Gram-negative bacteria. Recently, tetracyclines (TTCs) were found to prevent the patho-physiological changes associated with LPS in vivo and the secretion of inflammatory mediators in vitro. However, the mechanism by which TTCs prevents LPS-induced pathology in vivo is still unclear. In order to shed light on that problem, we carried out in vitro and in vivo experiments. TTC inhibited the secretion of nitric oxide (NO) and TNFa from LPSstimulated macrophages and inhibited macrophage-induced thymocyte proliferation. However, TTC inhibited NO secretion with use of concentrations five-fold lower than those that inhibited TNFα secretion and thymocyte proliferation. The secretion of NO was inhibited by the addition of TTC to the cultures up to 6 hrs post-LPS stimulation. TTC inhibition of LPS-induced NO secretion was not reversed by the addition of recombinant TNFa, and TTC inhibition of LPS-induced TNFa secretion was not reversed by the addition of NO donor. These results suggest that the inhibition of TNFa by TTC is not the result of the inhibition of LPS-induced NO secretion or vice versa. In vivo experiments had shown that TTC prevented mortality in LPS-treated mice, but not in mice pre-sensitized with galactosamine prior to the LPS challenge. These results suggest that TTC activity in vivo is due not to the suppression of synthesis of inflammatory mediators but rather to the induction of acute phase-like response, which antagonizes the LPS-induced activity.
Tetracyclines Inhibit Connective Tissue Breakdown by Multiple Non-Antimicrobial Mechanisms
Authors: Golub L.M. , Lee H.-M. , Ryan M.E. , Giannobile W.V. , Payne J. , Sorsa T.
Published: January 2009

A seminal experiment involving a germ-free rat model of connective tissue breakdown (followed soon thereafter by a series of in vitro studies) identified an unexpected non-antimicrobial property of tetracyclines (TCs). This ability of TCs to inhibit matrix metalloproteinases (MMPs) such as collagenase was found to reflect multiple direct and indirect mechanisms of action, and to be therapeutically useful in a variety of dental (e.g., adult periodontitis) and medical (e.g., arthritis, osteoporosis, cancer) diseases. The site on the TC molecule responsible for its MMP-inhibitory activity was identified which led to the development of a series of chemically modified non-antimicrobial analogs, called CMTs, which also have therapeutic potential but do not appear to induce antibiotic side-effects. Longitudinal double-blind studies on humans with adult periodontitis have demonstrated that a sub-antimicrobial dose of doxycycline (previously reported to suppress collagenase activity in the periodontal pocket) is safe and effective and has recently been approved by the FDA as an adjunct to scaling and root planing.
Modulation of Nitric Oxide Production by Tetracyclines and Chemically Modified Tetracyclines
Authors: Cillari E. , Milano S. , D'Agostino P. , Di Bella G. , La Rosa M. , Barbera C. , Ferlazzo V. , Cammarata G. , Grimaudo S. , Tolomeo M. , Feo S.
Published: January 2009

Chemically modified tetracyclines (CMTs) dose-dependently decreased inducible nitric oxide synthase (iNOS) and, consequently, nitric oxide (NO) formation by the lipopolysaccharide (LPS)-stimulated J774 line. The inhibitory effect was due to a specific reduction in the iNOS protein content in the cells, as attested by Western blot analysis and by the inhibition of iNOS mRNA accumulation. Furthermore, CMTs cause a dose-dependent increase in cell death in the J774 line mediated by the NO-independent apoptotic mechanism.
The Effects of Chemically Modified Tetracyclines (CMTs) on Human Keratinocyte Proliferation and Migration
Authors: Mäkelä M. , Sorsa T. , Uitto V.-J. , Salo T. , Teronen O. , Larjava H.
Published: January 2009

Chemically modified non-antimicrobial tetracycline derivatives and other low-molecular-weight synthetic matrix metalloproteinase (MMP) inhibitors inhibited keratinocyte migration. Since 72-kDa gelatinase-A (MMP-2) was the major gelatinase in our culture conditions, the results suggest that this MMP may be important in the regulation of keratinocyte mobility. On the other hand, we measured only gelatinase activities (MMP-2 and -9) present in culture medium, and therefore the results do not reveal how the inhibitors affect other MMPs as well as MMP levels close to the cell membranes. Overall, CMTs were found to be efficient in the inhibition of keratinocyte migration.
Tetracycline Derivatives Induce Apoptosis Selectively in Cultured Monocytes and Macrophages but not in Mesenchymal Cells
Authors: Bettany J.T. , Wolowacz R.G.
Published: January 2009

Evidence for a non-antibiotic activity displayed by certain tetracycline derivatives is presented. This activity is a selective cytotoxicity toward cells of the monocytic lineage (the human histiocytic lymphoma U937 cell line and the mouse macrophage line RAW264) but not toward various cells of a mesenchymal lineage (including primary ovine articular chondrocytes and meniscal cells, murine calvarial osteoblasts and MG-63 osteosarcoma cells, and primary human neonatal foreskin fibroblasts). Cells were incubated with various chemically modified tetracycline derivatives (CMTs) or doxycycline for 24 hrs at a range of concentrations between zero and 50 μg/mL in both serum-containing and serum-free culture conditions. Assessment of cell viability by means of the MTT assay demonstrated a potent dose-dependent cytotoxic effect induced by compound CMT-3 and a less potent effect induced by doxycycline, but no apparent cytotoxic effect in the presence of either CMT-2 or CMT-5. Cytospin preparations analyzed by the labeling of DNA fragments indicated the same trends and suggested that cell death was via an apoptotic mechanism. The cytotoxic potency of these tetracyclines toward cells of the monocytic lineage could be diminished but not abolished by either the presence of 10% fetal calf serum within the culture medium, or pre-treatment with phorbol esters to promote a more macrophage-like phenotype. These data provide evidence that, in addition to well-characterized antibiotic and MMPinhibitory characteristics, tetracyclines may function by a novel mechanism to induce selective apoptosis.
Topically Applied Cmt-2 Enhances Wound Healing in Streptozotocin Diabetic Rat Skin
Authors: Ramamurthy N.S. , Kucine A.J. , McClain S.A. , McNamara T.F. , Golub L.M.
Published: January 2009

Delayed wound healing is one of the complications of diabetes mellitus, exhibited by increased wound collagenase and decreased granulation tissues. The current study compared wound healing in normal and diabetic rats, and the effects of topically applied 1 % or 3% concentrations of chemically modified tetracycline-2 (CMT-2) on 6-mm circular full-thickness skin wounds healed by secondary intention. On day 7 after wounding, tissues were removed for biochemical analysis and histology. The wound granulation tissue hydroxyproline was less in the untreated diabetic rat with increased collagenase and gelatinase. Treating the diabetic rat wounds with 3% CMT-2 increased the wound hydroxyproline and decreased activities of gelatinase and collagenase. There was a delay in wound filling by granulation tissue in diabetic rats. In CMT-2-treated diabetic rats, the volume of granulation tissue was greater than that in untreated diabetic rats. CMT-2 appears to normalize wound healing in diabetic rats and may be a valuable adjunct in the treatment of chronic wounds.
Tetracyclines Inhibit Protein Glycation in Experimental Diabetes
Authors: Ryan M.E. , Ramamurthy N.S. , Golub L.M.
Published: January 2009

Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi- fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals.
Therapeutic Potential of Tetracycline Derivatives to Suppress the Growth of Abdominal Aortic Aneurysms
Authors: Thompson R.W. , Liao S. , Curci J.A.
Published: January 2009

Abdominal aortic aneurysms (AAA) represent a potentially lethal disorder associated with aging and atherosclerosis. Although current management of AAA is predicated on early detection and elective surgical repair, routine screening for AAA is infrequent, because most AAA are too small to warrant repair when first detected and because there are no therapeutic approaches proven to suppress aneurysm expansion. Basic research on this problem suggests that chronic inflammation and increased local production of elastin-degrading proteinases play prominent roles in the process of aneurysmal degeneration. Members of the matrix metalloproteinases (MMP) family appear to be the most prominent elastases produced in human AAA, suggesting that unique therapeutic targets might exist for aneurysm disease. Studies using a representative animal model for AAA support this view, providing a means for further development of pharmacological approaches to suppress aneurysm expansion. Indeed, recent work indicates that tetracycline derivatives have the potential to interrupt the progressive connective tissue destruction that occurs in AAA, by virtue of their non-antimicrobial properties as MMP inhibitors, and they do so at clinically achievable dose schedules. These findings support the view that MMPs are potentially important pharmacotherapeutic targets in AAA and, moreover, that tetracyclines might be useful in suppressing aneurysm expansion in vivo. Because tetracycline derivatives offer a number of distinct advantages as MMP inhibitors for patients with small AAA, prospective clinical trials of this novel therapeutic strategy can be anticipated in the near future.
Long-Term Sub-Antimicrobial Doxycycline (Periostat®) as Adjunctive Management in Adult Periodontitis: Effects on Subgingival Bacterial Population Dynamics
Authors: Thomas J.G. , Metheny R.J. , Karakiozis J.M. , Wetzel J.M. , Crout R.J.
Published: January 2009

Previous trials had indicated that various schedules of sub-antimicrobial doxycycline significantly reduced gingival crevicular fluid (GCF) collagenase activity in adult patients with periodontitis with no evidence of emergent tetracycline-resistant (Tcr) marker oral flora. The purpose of this nine-month study was to expand these observations, emphasizing newer microbial diagnostic methods. Subgingival paper point samples were obtained at baseline (BL), 3, 6, and 9 months. Four subject treatment groups in a double-blind design were evaluated by mechanical scaling and root planing (SRP) and/or 20 mg doxycycline BID (Periostat®). Thirty-eight patients entered the study at baseline (BL). Dark-field microscopy on 260 samples showed that morphotype distribution was independent of treatment schedule. Culture analysis of the 3 most prevalent isolates recovered showed that Streptococcus and Prevotella species accounted for approximately 85% of the 724 cultures. There did not appear to be any overgrowth or replacement by opportunistic oral flora. Of 658 susceptibility patterns evaluated by Etest, the MIC 50/90 and mode MIC showed stable patterns, independent of treatment group. Our findings were different from those of previously published reports, but may be partly explained by the lack of universally standardized methods in oral microbiology and interpretive criteria for susceptibility testing.
Radiographic Determinants of Implant Performance
Authors: Reddy Michael S. , Wang I-Chung
Published: January 2009

This paper reviews and compares the strengths and weaknesses of radiographic techniques including periapical, occlusal, panoramic, direct digital, motion tomography, and computed tomography. Practical considerations for each method, including availability and accessibility, are discussed. To date, digital subtraction radiography is the most versatile and sensitive method for measuring boss loss. It can detect both bone height and bone mass changes on root-form or blade-form dental implants. Criteria for implant success have changed substantially over the past two decades. In clinical trials of dental implants, the outcomes require certain radiographic analyses to address the hypothesis or clinical question adequately. Radiographic methods best suited to the objective assessment of implant performance and hypothesis were reviewed.
Ceramic-Coated Implant Systems
Authors: Meffert Roland M.
Published: January 2009

Practitioners have used hydroxyapatite-coated (HA-coated) endosseous and subperiosteal implants in various forms for many years. These have included root forms in both screw and cylindrical shapes, blades, and subperiosteals. The clinical predictability remains controversial and subject to claims and counterclaims. The early days of dental implantology involving root-form implants recommended their placement in fully edentulous cases only, and anterior to the maxillary sinus and mental foramen. Today's philosophy and rationale of dental implantology include the placement of a single implant replacing a missing natural tooth (especially where the teeth adjacent to the edentulous site have no caries or restorative experience). Implants are used to replace the natural dentition in one quadrant/segment, often preceded or accompanied by ridge augmentation and/or sinus grafting if sufficient bone is not present. So we have to address the clinical predictability of survival in terms of indications, quantity, and quality of bone. Clinical data and experience suggest that hydroxyapatite-coated (HA) dental implants may (and possibly should) be used in (1) Type IV bone, (2) fresh extraction sites, (3) grafted maxillary and/or nasal sinuses, or (4) with short implants (≤ 10 mm in length).
The Biologic Tissue Responses to Uncoated and Coated Implanted Biomaterials
Authors: Steflik D.E. , Corpe R.S. , Young T.R. , Sisk A.L. , Parr G.R.
Published: January 2009

Ultrastructural examination of the morphology and morphometry of the bone supporting uncoated titanium and ceramic implants was assessed in an experimental animal model involving 120 implants placed into the mandibles of 30 adult mongrel dogs. Further, preliminary morphologic and morphometric observations of the bone supporting uncoated and hydroxylapatite-coated endosteal titanium implants was evaluated in a second investigation involving 72 implants placed into the mandibles and maxillae of 6 additional dogs. A densely mineralized collagen fiber matrix was observed directly interfacing with uncoated implants. The only material interposed between the implant and bone matrix was a 20- to 50-nm electron-dense material suggestive of a proteoglycan. Also seen in these same osseointegrated implants were narrow unmineralized zones interposed between the implant and bone matrix. In these zones of remodeling bone, numerous osteoblasts were observed interacting with the collagen fiber matrix. It was shown that a normal homeostasis of anabolic osteoblastic activity and catabolic osteoclastic activity resulted in bone remodeling and the resultant osseointegration of the implants. Hydroxylapatite-coated implants intimately interfaced with healthy bone. The mineralized matrix extended into the microporosity of the HA coating. This matrix contained viable osteocytes.
Role of the Osteoclast at the Bone-Implant Interface
Authors: Minkin C. , Marinho V.C.
Published: January 2009

A thorough understanding of the processes of healing, repair, and remodeling of bone is critical for the establishment and maintenance of osseointegration of dental implants. In this regard, much attention has been paid to the anabolic aspects of bone remodeling, including the cell biology of the osteoblast and the various cytokines and growth factors which regulate these processes. In contrast, there is little information on the bone-resorptive activity that occurs around implants during osseointegration, and of the role of osteoclasts, macrophages, and stromal cells in those catabolic processes associated with bone remodeling. This paper reviews osteoclast cell biology, the interaction of osteoclasts and biomaterials, and the information available on osteoclasts and dental implants, and poses some questions for future research.
In Vitro Models of Biological Responses to Implant Microbiological Models
Authors: Mombelli Andrea
Published: January 2009

To study the etiology and explore possibilities for the therapy of implant-associated infections, investigators have developed and utilized various in vitro models. Major contributions have come from the non-oral medical field, where device-related infections can create life-threatening situations. Microbiological models may include (i) models to study the reaction of micro-organisms to the presence of implants, (ii) models to study the reaction of implant-associated micro-organisms to antimicrobial agents, and (iii) models to study the reaction of the host tissues to the presence of implants contaminated with micro-organisms. In evaluating the potential usefulness of these models for research in oral implantology, one must consider common features as well as important differences between implanted medical devices and oral implants. Although infections associated with implantable medical devices and oral peri-implant infections share a remarkable number of common features, there are also important differences that need attention when findings from in vitro experiments are extrapolated to clinical relevance.
Implant Surfaces and Interface Processes
Authors: Kasemo B. , Gold J.
Published: January 2009

The past decades and current R&D of biomaterials and medical implants show some general trends. One major trend is an increased degree of functionalization of the material surface, better to meet the demands of the biological host system. While the biomaterials of the past and those in current use are essentially bulk materials (metals, ceramics, polymers) or special compounds (bioglasses), possibly with some additional coating (e.g., hydroxyapatite), the current R&D on surface modifications points toward much more complex and multifunctional surfaces for the future. Such surface modifications can be divided into three classes, one aiming toward an optimized three-dimensional physical micro-architecture of the surface (pore size distributions, "roughness", etc.), the second one focusing on the (bio) chemical properties of surface coatings and impregnations (ion release, multi-layer coatings, coatings with biomolecules, controlled drug release, etc.), and the third one dealing with the viscoelastic properties (or more generally the micromechanical properties) of material surfaces. These properties are expected to affect the interfacial processes cooperatively, i.e., there are likely synergistic effects between and among them: The surface is "recognized" by the biological system through the combined chemical and topographic pattern of the surface, and the viscoelastic properties. In this presentation, the development indicated above is discussed briefly, and current R&D in this area is illustrated with a number of examples from our own research. The latter include micro- and nanofabrication of surface patterns and topographies by the use of laser machining, photolithographic techniques, and electron beam and colloidal lithographies to produce controlled structures on implant surfaces in the size range 10 nm to 100 μm. Examples of biochemical modifications include mono- or lipid membranes and protein coatings on different surfaces. A new method to evaluate, e.g., biomaterial-protein and biomaterial-cell interactions-the Quartz Crystal Microbalance-is described briefly.
In Vivo Bone Response to Biomechanical Loading at the Bone/Dental-Implant Interface
Authors: Brunski John B.
Published: January 2009

Since dental implants must withstand relatively large forces and moments in function, a better understanding of in vivo bone response to loading would aid implant design. The following topics are essential in this problem. (1) Theoretical models and experimental data are available for understanding implant loading as an aid to case planning. (2) At least for several months after surgery, bone healing in gaps between implant and bone as well as in pre-existing damaged bone will determine interface structure and properties. The ongoing healing creates a complicated environment. (3) Recent studies reveal that an interfacial cement line exists between the implant surface and bone for titanium and hydroxyapatite (HA). Since cement lines in normal bone have been identified as weak interfaces, a cement line at a bone-biomaterial interface may also be a weak point. Indeed, data on interfacial shear and tensile "bond" strengths are consistent with this idea. (4) Excessive interfacial micromotion early after implantation interferes with local bone healing and predisposes to a fibrous tissue interface instead of osseointegration. (5) Large strains can damage bone. For implants that have healed in situ for several months before being loaded, data support the hypothesis that interfacial overload occurs if the strains are excessive in interfacial bone. While bone "adaptation" to loading is a long-standing concept in bone physiology, researchers may sometimes be too willing to accept this paradigm as an exclusive explanation of in vivo tissue responses during experiments, while overlooking confounding variables, alternative (non-mechanical) explanations, and the possibility that different types of bone ( e.g., woven bone, Haversian bone, plexiform bone) may have different sensitivities to loading under healing vs. quiescent conditions.
Constitutions and Policy Comparisons
Authors: Hugh-Jones David
Published: January 2009

Voters in democracies can learn from the experience of neighbouring states: about policy in a direct democracy (`policy experimentation'), about the quality of their politicians in a representative democracy (`yardstick competition'). Learning between states creates spillovers from policy choice, and also from constitutional choice. I model these spillovers in a simple principal-agent framework, and show that voter welfare may be maximized by a mixture of representative and direct democratic states. Because of this, empirical work examining voter welfare under direct democracy may need to be reinterpreted. Also, I show that the optimal mix of constitutions cannot always be achieved in a constitutional choice equilibrium involving many states.
Making Making Social Science Matter Matter To Us
Authors: Adcock Robert
Published: January 2009

This article pursues two line of inquiry in response to Bent Flyvbjerg's advocacy of a phronetic social science in Making Social Science Matter (2001). First, I explore how Flyvbjerg's manifesto relates to the approach employed in his earlier empirical work, Rationality & Power (1998). There are, I argue, notable disjunctions between the practice of Rationality & Power and the preaching of Making Social Science Matter. Second, I explicate and rework Flyvbjerg's contrast between epistemic and phronetic social science with an eye to its reception by a specific disciplinary audience: American political scientists. In doing so, I build on several contributions to Sanford Schram and Brian Caterino's edited volume Making Political Science Matter (2006). My aspiration is, however, rather different from that of the volume: I strive to make epistemic and phronetic into accessible categories of reformist reflection, not provocative banners under which to marshal revolutionary opposition to our disciplinary mainstream(s).
The Leader Rule
Authors: Laslier Jean-François
Published: January 2009

The article considers Approval Voting for a large population of voters. It is supposed that voters evaluate the relative likelihood of pairwise ties among candidates based on statistical information about candidate scores. This leads them to vote sincerely and according to a simple behavioral rule we call the `Leader Rule'. At equilibrium, if a Condorcet-winner exists, this candidate is elected.
Towards a European Union Gender Equality Index
Authors: Plantenga Janneke , Remery Chantal , Figueiredo Hugo , Smith Mark
Published: January 2009

In order to monitor progress with respect to gender equality in European Union member states, indices are extremely useful. Existing indices are, however, not appropriate because they do not focus exclusively on gender (in)equality and have not been created to be used at the European level. Therefore a European Union Gender Equality Index is presented in this article. Based on the universal caregiver model as outlined by Fraser (1997), the index is composed of four dimensions: equal sharing of paid work, money, decision-making power and time. With regard to the applied methodology, the index is constructed in such a way that the value indicates the actual distance from a situation of full equality. The empirical results show that full equality is still a long way off. Finland, Sweden and Denmark display the highest overall performance, whereas the southern countries — Greece, Cyprus, Malta, Spain and Italy — perform rather poorly.
Do welfare-to-work initiatives work? Evidence from an activation programme targeted at social assistance recipients in Norway
Authors: Rønsen Marit , Skarðhamar Torbjørn
Published: January 2009

The emphasis on welfare-to-work policies across Europe has led to increased interest in active labour market programmes. A recent trend in some countries is a tighter collaboration between different welfare agencies and the inclusion of very disadvantaged groups. Few studies have evaluated such broad programmes. In this article we evaluate a Norwegian initiative to combat poverty, which is mainly directed at social assistance recipients, and which involves a close cooperation between the Employment Service and the Social Welfare System. We illuminate short-term effects, taking a dual approach: First, we analyse transitions to work among programme participants and study the determinants of this process by means of survival analysis. Second, we address the question of programme effects using propensity score matching. We find that the mean programme effect is positive, but varying across target groups. For immigrants and single mothers there is no impact. For youth the effect may even be negative. The only significant effect in the desired direction is found among long-term social assistance recipients, and this effect is fairly large.
The Impact of Molecular Genetics on Oral Health Paradigms
Authors: Hart T.C. , Marazita M.L. , Wright J.T.
Published: January 2009

As a result of our increased understanding of the human genome, and the functional interrelationships of gene products with each other and with the environment, it is becoming increasingly evident that many human diseases are influenced by heritable alterations in the structure or function of genes. Significant advances in research methods and newly emerging partnerships between private and public sector interests are creating new possibilities for utilization of genetic information for the diagnosis and treatment of human diseases. The availability and application of genetic information to the understanding of normal and abnormal human growth and development are fundamentally changing the way we approach the study of human diseases. As a result, the issues and principles of medical genetics are coming to bear across all disciplines of health care. In this review, we discuss some of the potential applications of human molecular genetics for the diagnosis and treatment of oral diseases. This discussion is presented in the context of the ongoing technological advances and conceptual changes that are occurring in the field of medical genetics. To realize the promise of this new molecular genetics, we must be prepared to foresee the possibilities and to incorporate these newly emergent technologies into the evolving discipline of dentistry. By using examples of human conditions, we illustrate the broad application of this emerging technology to the study of simple as well as complex genetic diseases. Throughout this paper, we will use the following terminology: P enetrance—I n a population, defined as the proportion of individuals posessing a disease-causing genotype who express the disease phenotype. When this proportion is less than 100%, the disease is said to have reduced or incomplete penetrance. Polymerase chain reaction (PCR)-A technique for amplifying a large number of copies of a specific DNA sequence flanked by two oligonucleotide primers. The DNA is alternately heated and cooled in the presence of DNA polymerase and free nucleotides, so that the specified DNA segment is denatured, hybridized with primers, and extended by DNA polymerase. MIM-Mendelian Inheritance in Man catalogue number from V. McKusick's Mendelian Inheritance in man (OMIM, 1998).
Biomarkers and Molecular Epidemiology and Chemoprevention of Oral Carcinogenesis
Authors: Schwartz Joel L.
Published: January 2009

Chemopreventives are chemicals that prevent the formation of cancers such as oral cancer. They can take the form of nutrients or synthetic molecules, and their fundamental characteristic is that they do not produce disease processes that would result in debilitating symptoms. Current evidence indicates that they function by modifying the oxidative state of transforming cells. Biomarkers can take the form of genetic and molecular indicators, which characterize the function of chemopreventives and cancer processes such as oral carcinogenesis. Biomarkers cannot provide all the required information for risk assessment or possible activity of the chemopreventives. Other methods, such as epidemiological analyses and techniques, must be used to enhance our understanding of the risk for oral cancer in human populations. One common epidemiologic method, the questionnaire, helps to determine the use and carcinogenic potential of tobacco and alcohol during oral carcinogenesis. Genetic and molecular changes in human patient populations may result in a reduction in the number and function of tumor suppressor genes. If these changes are to be assessed, the tissues ( e. g., buccal mucosa) must be accessible and harvested in a reliable and consistent manner for the acquisition of DNA, mRNA, and protein. Oral tissues provide sufficient quantities of these molecules and, under stringent conditions, the quality required for the isolation of these molecular constituents. In conjunction with epidemiologic techniques, various genotypic polymorphisms, such as glutathione-S-transferase (GSTM 1) or cytochrome P 450 (CYP450Al), have indicated a loss in carcinogen detoxification or the processing of internal growth control signals. Biomarkers are composed of a large diverse group of genetic and molecular structures. Some of these biomarkers are indicators for programmed cell death (PCD), while others describe malignant tumor growth. Many of these classes of molecules are oxidative-responsive ( e.g., tumor suppressor p53, Bcl-2, growth factors, immune-derived proteins, and death-inducing molecules) and induce PCD by triggering a cascade of cysteine proteases and regulators ( e. g., caspases, death receptors). This pathway results in cell-cycle alterations and DNA fragmentation. It is hoped that a detailed knowledge of the processes involved in malignant transformation will better define the biomarker-screening tools for oral cancer. These tools will enhance our ability to predict the incidence of cancer, detect early malignant change, and quantitate chemoprevention during oral carcinogenesis. Chemopreventives such as the retinoids have already demonstrated their ability to suppress potential malignant changes in pre-malignant oral leukoplakias and decrease the incidence of second head-and-neck cancer primaries. It is our hope that this review will increase investigators' interest in developing new screening and detection systems for oral cancer.
Oral Candidal Infections and Antimycotics
Authors: Ellepola A.N.B. , Samaranayake L.P.
Published: January 2009

The advent of the human immunodeficiency virus infection and the increasing prevalence of compromised individuals in the community due to modern therapeutic advances have resulted in a resurgence of opportunistic infections, including oral candidoses. One form of the latter presents classically as a white lesion of "thrush" and is usually easily diagnosed and cured. Nonetheless, a minority of these lesions appears in new guises such as erythematous candidosis, thereby confounding the unwary clinician and complicating its management. Despite the availability of several effective antimycotics for the treatment of oral candidoses, failure of therapy is not uncommon due to the unique environment of the oral cavity, where the flushing effect of saliva and the cleansing action of the oral musculature tend to reduce the drug concentration to sub-therapeutic levels. This problem has been partly circumvented by the introduction of the triazole agents, which initially appeared to be highly effective. However, an alarming increase of organisms resistant to the triazoles has been reported recently. In this review, an overview of clinical manifestations of oral candidoses and recent advances in antimycotic therapy is given, together with newer concepts, such as the post-antifungal effect (PAFE) and its possible therapeutic implications.