Diabetes Aggravates Periodontitis by Limiting Repair Through Enhanced Inflammation

Periodontitis is the most common lytic bone disease and one of the first clinical manifestations of diabetes. Diabetes increases the risk of periodontitis. The aim of the present study was to examine mechanisms by which diabetes aggravates periodontitis. Ligature-induced periodontitis was examined in Goto-Kakizaki rats with type 2 diabetes. A tumor necrosis factor (TNF)-specificinhibitor, pegsunercept, was applied to diabetic rats after the onset of periodontal disease. Interferon-γ (IFN-γ), TNF-α, interleukin-1 β (IL-1β), fibroblast growth factor-2 (FGF-2), transforming growth factor beta-1 (TGFβ-1), bone morphogenetic protein-2 (BMP-2), and BMP-6 were measured by real-time RT-PCR, and histological sections were examined for leukocyte infiltration and several parameters related to bone resorption and formation. Inflammation was prolonged in diabetic rats and was reversed by the TNF inhibitor, which reduced cytokine mRNA levels, leukocyte infiltration, and osteoclasts. In contrast, new bone and osteoid formation and osteoblast numbers were increased significantly vs. untreated diabetic animals. TNF inhibition in diabetic animals also reduced apoptosis, increased proliferation of bone-lining cells, and increased mRNA levels of FGF-2, TGFβ-1, BMP-2, and BMP-6. Thus, diabetes prolongs inflammation and osteoclastogenesis in periodontitis and through TNF limits the normal reparative process by negatively modulating factors that regulate bone. © FASEB

Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B.

Bacterial pathogens stimulate periodontitis, the most common osteolytic disease in humans and the most common cause of tooth loss in adults. Previous studies identified leukocytes and their products as key factors in this process. We demonstrate for the first time that osteoblast lineage cells play a critical role in periodontal disease. Oral infection stimulated nuclear localization of NF-κB in osteoblasts and osteocytes in the periodontium of wild type but not transgenic mice that expressed a lineage specific dominant negative mutant of IKK (IKK-DN) in osteoblast lineage cells. Wild-type mice were also susceptible to bacteria induced periodontal bone loss but transgenic mice were not. The lack of bone loss in the experimental group was linked to reduced RANKL expression by osteoblast lineage cells that led to diminished osteoclast mediated bone resorption and greater coupled new bone formation. The results demonstrate that osteoblast lineage cells are key contributors to periodontal bone loss through an NF-κB mediated mechanism

NF-κB has a Direct Role in Inhibiting Bmp- and Wnt-Induced Matrix Protein Expression.

The host response to pathogens through nuclear factor κB (NF-κB) is an essential defense mechanism for eukaryotic organisms. NF-κB-mediated host responses inhibit bone and other connective tissue synthesis and are thought to affect the transcription of matrix proteins through multiple indirect pathways. We demonstrate that inhibiting NF-κB in osteoblasts increases osteocalcin expression in vivo in mice with periodontal disease. Mutating NF-κB binding sites on osteocalcin (OC) or bone sialoprotein (Bsp) promoters rescues the negative impact of NF-κB on their transcription and that NF-κB can inhibit Wnt- and Bmp-induced OC and Bsp transcription, even when protein synthesis is inhibited, indicating a direct effect of NF-κB. This inhibition depends on p65-p50 NF-κB heterodimer formation and deacetylation by HDAC1 but is not affected by the noncanonical NF-κB pathway. Moreover, NF-κB reduces Runx2 and β-catenin binding to OC/Bsp promoters independently of their nuclear localization. Thus, inflammatory signals stimulate the direct interaction of NF-κB with response elements to inhibit binding of β-catenin and Runx2 binding to nearby consensus sites and reduce expression of matrix proteins. This direct mechanism provides a new explanation for the rapid decrease in new bone formation after inflammation-related NF-κB activation

Chemical Synthesis of PEDOT–Au Nanocomposite

In this work, gold-incorporated polyethylenedioxythiophene nanocomposite material has been synthesized chemically, employing reverse emulsion polymerization method. Infrared and Raman spectroscopic studies revealed that the polymerization of ethylenedioxythiophene leads to the formation of polymer polyethylenedioxythiophene incorporating gold nanoparticles. Scanning electron microscope studies showed the formation of polymer nanorods of 50–100 nm diameter and the X-ray diffraction analysis clearly indicates the presence of gold nanoparticles of 50 nm in size

Aggregatibacter actinomycetemcomitans Infection Enhances Apoptosis In Vivo through a Caspase-3-Dependent Mechanism in Experimental Periodontitis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced by Aggregatibacter actinomycetemcomitans infection. Thirty-eight diabetic and 33 normal rats were inoculated with A. actinomycetemcomitans and euthanized at baseline and at 4, 5, and 6 weeks after inoculation. Bone loss and the infiltration of polymorphonuclear leukocytes (PMNs) in gingival epithelium were measured in hematoxylin-eosin-stained sections. The induction of tumor necrosis factor alpha (TNF-alpha) was evaluated by immunohistochemistry and of apoptotic cells by a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay. After A. actinomycetemcomitans infection, the bone loss in diabetic rats was 1.7-fold and the PMN infiltration 1.6-fold higher than in normoglycemic rats (P < 0.05). The induction of TNF-alpha was 1.5-fold higher and of apoptotic cells was up to 3-fold higher in diabetic versus normoglycemic rats (P < 0.05). Treatment with a caspase-3 inhibitor significantly blocked noninflammatory cell apoptosis induced by A. actinomycetemcomitans infection in gingival epithelium and connective tissue (P < 0.05). These results provide new insight into how diabetes aggravates A. actinomycetemcomitans-induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection.80622472256NIDCR [DE018307, DE017732]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)NIDCR [DE018307, DE017732

A first-principles approach to electrical transport in atomic-scale nanostructures

We present a first-principles numerical implementation of Landauer formalism for electrical transport in nanostructures characterized down to the atomic level. The novelty and interest of our method lies essentially on two facts. First of all, it makes use of the versatile Gaussian98 code, which is widely used within the quantum chemistry community. Secondly, it incorporates the semi-infinite electrodes in a very generic and efficient way by means of Bethe lattices. We name this method the Gaussian Embedded Cluster Method (GECM). In order to make contact with other proposed implementations, we illustrate our technique by calculating the conductance in some well-studied systems such as metallic (Al and Au) nanocontacts and C-atom chains connected to metallic (Al and Au) electrodes. In the case of Al nanocontacts the conductance turns out to be quite dependent on the detailed atomic arrangement. On the contrary, the conductance in Au nanocontacts presents quite universal features. In the case of C chains, where the self-consistency guarantees the local charge transfer and the correct alignment of the molecular and electrode levels, we find that the conductance oscillates with the number of atoms in the chain regardless of the type of electrode. However, for short chains and Al electrodes the even-odd periodicity is reversed at equilibrium bond distances.Comment: 14 pages, two-column format, submitted to PR

On the unipolarity of charge transport in methanofullerene diodes

Fullerenes are electron transporting organic semiconductors with a wide range of applications. In particular, methanofullereneshave been the preferred choice for solution-processed solar cells and photodiodes. The wide applicability of fullerenes as both ‘ntype’transport materials and electron acceptors is clear. However, what is still a matter of debate is whether the fullerenes can alsosupport efficient transport of holes, particularly in diode geometries. In this letter, we utilize a number of recently developedexperimental methods for selective electron and hole mobility measurements. We show for the two most widely used solutionprocessable fullerenes, PC70- and-PC60BM, that whilst both exhibit electron mobilities as high as 10−3 cm2/Vs, their hole mobilities

Sigmatropic rearrangements in 5-allyloxytetrazoles

Mechanisms of thermal isomerization of allyl tetrazolyl ethers derived from the carbocyclic allylic alcohols cyclohex-2-enol and 3-methylcyclohex-2-enol and from the natural terpene alcohol nerol were investigated. In the process of the syntheses of the three 1-aryl-5-allyloxytetrazoles, their rapid isomerization to the corresponding 1-aryl-4-allyltetrazol-5-ones occurred. The experiments showed that the imidates rearrange exclusively through a [3,3¢]-sigmatropic migration of the allylic system from O to N, with inversion. Mechanistic proposals are based on product analysis and extensive quantum chemical calculations at the DFT(B3LYP) and MP2 levels, on O-allyl and N-allyl isomers and on putative transition state structures for [1,3¢]- and [3,3¢]-sigmatropic migrations. The experimental observations could be only explained on the basis of the MP2/6-31G(d,p) calculations that favoured the [3,3¢]-sigmatropic migrations, yielding lower energies both for the transition states and for the final isomerization products

Comparison of phase structures and surface free energy values for the coatings synthesised from linear polyurethanes and from waterborne polyurethane cationomers

WAXS, DSC and AFM methods were employed to compare phase structures of the coatings obtained from waterborne polyurethane cationomers which had been synthesised in the reaction of some diisocyanates (MDI, IPDI, TDI and HDI) with polyoxyethylene glycols (M = 600 and 2,000) and butane1,4-diol or N-methyl- or N-butyldiethanolamine and 2,2,3,3-tetrafluoro-1,4-butanediol. The structures were also analysed of the coatings derived from linear polyurethanes which had been synthesised on the basis of similar raw materials. Better rigidity was found for generally amorphous cationomer coats. Changes were discussed in the surface free energy (SFE) values and in their components, as calculated independently with the use of the van Oss–Good and Owens–Wendt methods. Polyurethane coats turned out more hydrophobic as compared to cationomer ones. In both coat types, fluorine incorporated into cationomers contributed to lower SFE values: from 50 down to about 30 mJ/m2

Molecular diagnosis of Pseudoterranova decipiens s.s in human, France

Background: Anisakis and Pseudoterranova are the main genera involved in human infections caused by nematodes of the Anisakidae family. Species identification is complicated due to the lack of differential morphological characteristics at the larval stage, thus requiring molecular differentiation. Pseudoterranova larvae ingested through raw fish are spontaneously eliminated in most cases, but mechanical removal by means of endoscopy might be required. To date, only very few cases of Pseudoterranova infection have been reported in France. Case presentation: A 19-year-old woman from Northeastern France detected, while brushing her teeth, a larva exiting through her mouth. The patient who presented with headache, diarrhea, and abdominal cramps reported having eaten baked cod. The worm was a fourth-stage larva with a size of 22 × 0.9 mm, and molecular biology identified it as Pseudoterranova decipiens sensu stricto (s. s.). In a second P. decipiens infection case, occurring a few months later, a worm exited through the patient’s nose after she had eaten raw sea bream. Conclusion: These two cases demonstrate that Pseudoterranova infection is not uncommon among French patients. Therefore, molecular techniques should be more widely applied for a better characterization of anisakidosis epidemiology in France