The Evaluation of the School-Based Flouride Mouthrinse Program in a Fluoridated Community

The purpose of this study was to evaluate the effect of a school-based fluoride mouthrinse program in a fluoridated community. Such an evaluation is important because the effect of such programs may decrease over time due to the widespread use of fluoride. Two elementary schools were chosen. One had a fluoride mouthrinse program: the other did not. The subjects were children in grades one and six. Their caries experience was examined using dft. dfs. DFT, and DFS scores. There were no statistically significant differences between the two schools. The program had no significant effect in the community studied

A Case of Mycobacterial Skin Disease Caused by Mycobacterium peregrinum, and a Review of Cutaneous Infection

An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules on the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNA-DNA hybridization analysis, 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment

Mycobacterium ulcerans infection: control, diagnosis, and treatment.

The skin disease Buruli ulcer, caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy and mainly affects remote rural African communities. Although the disease is known to be linked to contaminated water, the mode of transmission is not yet understood, which makes it difficult to propose control interventions. The disease is usually detected in its later stages, when it has caused substantial damage and disability. Surgery remains the treatment of choice. Although easy and effective in the early stages of the disease, treatment requires extended excisions and long hospitalisation for the advanced forms of the disease. Currently, no antibiotic treatment has proven effective for all forms of M ulcerans infection and research into a new vaccine is urgently needed. While the scientific community works on developing non-invasive and rapid diagnostic tools, the governments of endemic countries should implement active case finding and health education strategies in their affected communities to detect the disease in its early stages. We review the diagnosis, treatment, and control of Buruli ulcer and list priorities for research and development

Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD

<p>Abstract</p> <p>Background</p> <p>Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM)17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis.</p> <p>Methods</p> <p>We studied the effects of cigarette smoke extract (CSE) and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs) from COPD patients, healthy smokers and non-smokers.</p> <p>Results</p> <p>We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP)-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding) was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups.</p> <p>Conclusions</p> <p>Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD.</p

Activation of Epidermal Growth Factor Receptor Is Required for NTHi-Induced NF-κB-Dependent Inflammation

Inflammation is a hallmark of many serious human diseases. Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen causing respiratory tract infections in both adults and children. NTHi infections are characterized by inflammation, which is mainly mediated by nuclear transcription factor-kappa B (NF-κB)-dependent production of proinflammatory mediators. Epidermal growth factor receptor (EGFR) has been shown to play important roles in regulating diverse biological processes, including cell growth, differentiation, apoptosis, adhesion, and migration. Its role in regulating NF-κB activation and inflammation, however, remains largely unknown.In the present study, we demonstrate that EGFR plays a vital role in NTHi-induced NF-κB activation and the subsequent induction of proinflammatory mediators in human middle ear epithelial cells and other cell types. Importantly, we found that AG1478, a specific tyrosine kinase inhibitor of EGFR potently inhibited NTHi-induced inflammatory responses in the middle ears and lungs of mice in vivo. Moreover, we found that MKK3/6-p38 and PI3K/Akt signaling pathways are required for mediating EGFR-dependent NF-κB activation and inflammatory responses by NTHi.Here, we provide direct evidence that EGFR plays a critical role in mediating NTHi-induced NF-κB activation and inflammation in vitro and in vivo. Given that EGFR inhibitors have been approved in clinical use for the treatment of cancers, current studies will not only provide novel insights into the molecular mechanisms underlying the regulation of inflammation, but may also lead to the development of novel therapeutic strategies for the treatment of respiratory inflammatory diseases and other inflammatory diseases

Discovery of a Novel hsp65 Genotype within Mycobacterium massiliense Associated with the Rough Colony Morphology

So far, genetic diversity among strains within Mycobacterium massiliense has rarely been studied. To investigate the genetic diversity among M. massiliense, we conducted phylogenetic analysis based on hsp65 (603-bp) and rpoB (711-bp) sequences from 65 M. massiliense Korean isolates. We found that hsp65 sequence analysis could clearly differentiate them into two distinct genotypes, Type I and Type II, which were isolated from 35 (53.8%) and 30 patients (46.2%), respectively. The rpoB sequence analysis revealed a total of four genotypes (R-I to R-IV) within M. massiliense strains, three of which (R-I, R-II and R-III) correlated with hsp65 Type I, and other (R-IV), which correlated with Type II. Interestingly, genotyping by the hsp65 method agreed well with colony morphology. Despite some exceptions, Type I and II correlated with smooth and rough colonies, respectively. Also, both types were completely different from one another in terms of MALDI-TOF mass spectrometry profiles of whole lipid. In addition, we developed PCR-restriction analysis (PRA) based on the Hinf I digestion of 644-bp hsp65 PCR amplicons, which enables the two genotypes within M. massiliense to be easily and reliably separated. In conclusion, two distinct hsp65 genotypes exist within M. massiliense strains, which differ from one another in terms of both morphology and lipid profile. Furthermore, our data indicates that Type II is a novel M. massiliense genotype being herein presented for the first time. The disparity in clinical traits between these two hsp65 genotypes needs to be exploited in the future study

Consequence of one-electron oxidation and one-electron reduction for aniline

Quantum-chemical calculations were performed for all possible isomers of neutral aniline and its redox forms, and intramolecular proton-transfer (prototropy) accompanied by π-electron delocalization was analyzed. One-electron oxidation (PhNH2 – e → [PhNH2]+•) has no important effect on tautomeric preferences. The enamine tautomer is preferred for oxidized aniline similarly as for the neutral molecule. Dramatical changes take place when proceeding from neutral to reduced aniline. One-electron reduction (PhNH2 + e → [PhNH2]-•) favors the imine tautomer. Independently on the state of oxidation, π- and n-electrons are more delocalized for the enamine than imine tautomers. The change of the tautomeric preferences for reduced aniline may partially explain the origin of the CH tautomers for reduced nucleobases (cytosine, adenine, and guanine)

Lysophosphatidate Induces Chemo-Resistance by Releasing Breast Cancer Cells from Taxol-Induced Mitotic Arrest

Taxol is a microtubule stabilizing agent that arrests cells in mitosis leading to cell death. Taxol is widely used to treat breast cancer, but resistance occurs in 25-69% of patients and it is vital to understand how Taxol resistance develops to improve chemotherapy. The effects of chemotherapeutic agents are overcome by survival signals that cancer cells receive. We focused our studies on autotaxin, which is a secreted protein that increases tumor growth, aggressiveness, angiogenesis and metastasis. We discovered that autotaxin strongly antagonizes the Taxol-induced killing of breast cancer and melanoma cells by converting the abundant extra-cellular lipid, lysophosphatidylcholine, into lysophosphatidate. This lipid stimulates specific G-protein coupled receptors that activate survival signals.In this study we determined the basis of these antagonistic actions of lysophosphatidate towards Taxol-induced G2/M arrest and cell death using cultured breast cancer cells. Lysophosphatidate does not antagonize Taxol action in MCF-7 cells by increasing Taxol metabolism or its expulsion through multi-drug resistance transporters. Lysophosphatidate does not lower the percentage of cells accumulating in G2/M by decreasing exit from S-phase or selective stimulation of cell death in G2/M. Instead, LPA had an unexpected and remarkable action in enabling MCF-7 and MDA-MB-468 cells, which had been arrested in G2/M by Taxol, to normalize spindle structure and divide, thus avoiding cell death. This action involves displacement of Taxol from the tubulin polymer fraction, which based on inhibitor studies, depends on activation of LPA receptors and phosphatidylinositol 3-kinase.This work demonstrates a previously unknown consequence of lysophosphatidate action that explains why autotaxin and lysophosphatidate protect against Taxol-induced cell death and promote resistance to the action of this important therapeutic agent

The Magnitude and Mechanism of Charge Enhancement of CH∙∙O H-bonds

Quantum calculations find that neutral methylamines and thioethers form complexes, with N-methylacetamide (NMA) as proton acceptor, with binding energies of 2–5 kcal/mol. This interaction is magnified by a factor of 4–9, bringing the binding energy up to as much as 20 kcal/mol, when a CH3+ group is added to the proton donor. Complexes prefer trifurcated arrangements, wherein three separate methyl groups donate a proton to the O acceptor. Binding energies lessen when the systems are immersed in solvents of increasing polarity, but the ionic complexes retain their favored status even in water. The binding energy is reduced when the methyl groups are replaced by longer alkyl chains. The proton acceptor prefers to associate with those CH groups that are as close as possible to the S/N center of the formal positive charge. A single linear CH··O hydrogen bond (H-bond) is less favorable than is trifurcation with three separate methyl groups. A trifurcated arrangement with three H atoms of the same methyl group is even less favorable. Various means of analysis, including NBO, SAPT, NMR, and electron density shifts, all identify the +CH··O interaction as a true H-bond