bluuebunny/crossref_metadata_2025 huggingface dataset:
A Determination of the Range of Oral Conditions Submitted for Microscopic and Direct Immunofluorescence Analysis
Authors: Rinaggio Joseph , Crossland David M. , Zeid Mohamed Y.
Published: October 2007

Background: Direct immunofluorescence (DIF) testing is a useful adjunct for the diagnosis of immune‐mediated oral vesiculobullous diseases, helping to identify separate, histologically similar, but prognostically different, conditions. It is unknown how often biopsy of these lesions yields positive DIF results.

Methods: A total of 270 consecutive archival cases submitted to a reference laboratory in Buffalo, New York, over a 2‐year span were examined. These specimens were submitted to establish or rule out a diagnosis of a DIF‐positive oral vesiculobullous disease. Demographic, clinical, and diagnostic information, based on conventional microscopic and DIF analysis, was tabulated. To assess the contribution of DIF to successful diagnosis, three pathologists examined the hematoxylin and eosin–stained slides of the known DIF‐positive specimens without knowledge of the DIF results.

Results: Approximately 48% of the specimens demonstrated positive DIF findings and consisted of pemphigus vulgaris, mucous membrane pemphigoid, lichen planus, linear immunoglobulin A disease, and chronic ulcerative stomatitis. The remaining specimens had negative DIF findings and consisted of numerous non‐specific inflammatory conditions. Of particular interest were several cases of epithelial dysplasia and squamous cell carcinoma. Of the DIF‐positive cases, only pemphigus vulgaris could be diagnosed reliably by conventional microscopy alone.

Conclusions: Approximately half of biopsies of oral conditions that clinically resembled typically DIF‐positive vesiculobullous diseases did not yield positive findings on DIF testing. Instead, a wide range of oral diseases can mimic these lesions clinically. With the exception of pemphigus vulgaris, DIF is essential for establishing a definitive diagnosis for known DIF‐positive diseases.
A p38 Mitogen‐Activated Protein Kinase Inhibitor Arrests Active Alveolar Bone Loss in a Rat Periodontitis Model
Authors: Rogers Jill E. , Li Fei , Coatney Derek D. , Otremba Jodie , Kriegl Jaclynn M. , Protter Andrew A. , Higgins Linda S. , Medicherla Satyanarayana , Kirkwood Keith L.
Published: October 2007

Background: Gram‐negative bacterial species, such as Actinobacillus actinomycetemcomitans, contain lipopolysaccharide (LPS) that initiates the innate immune system, resulting in inflammatory alveolar bone loss. LPS activates Toll‐like receptors on membrane surfaces, stimulating many intracellular signaling cascades, including the p38 mitogen‐activated protein kinase (MAPK). Activation of p38 signaling mediates inflammatory cytokine expression, contributing toward osteoclastogenesis and bone loss. The aim of this study was to determine whether the novel, orally active p38 MAPK inhibitor SD282 could arrest progression of LPS‐induced alveolar bone destruction in rats.

Methods: Three groups of female Sprague‐Dawley rats received LPS injections to the palatal molar gingiva three times per week for 4 weeks to establish periodontitis. From weeks 5 through 8, two groups received the drug SD282 (N = 14) or 1% polyethylene glycol drug vehicle (N = 14) via oral gavage in addition to LPS injections. The third group continued to receive only LPS injections (N = 8). Microcomputed tomography was used to measure volumetric alveolar bone loss, expressed as bone volume fraction (BVF). Expression of interleukin (IL)‐1 and ‐6 and tumor necrosis factor‐alpha (TNF‐α) was assessed by immunohistochemistry, and osteoclasts were enumerated by tartrate‐resistant acid phosphatase staining.

Results: By 4 weeks, severe alveolar bone resorption was seen in LPS‐injected animals. Administration of SD282 significantly blocked additional volumetric bone loss in the LPS‐only versus LPS + SD282 groups (0.37 ± 0.01 BVF versus 0.43 ± 0.01 BVF; P <0.01). Significant reductions in IL‐1β (P <0.01), TNF‐α (P <0.05), and osteoclast formation (P <0.01) occurred in the presence of SD282.

Conclusions: An orally active p38 MAPK inhibitor reduced LPS‐induced inflammatory cytokine expression, osteoclastogenesis, and alveolar bone loss in rats. Within the limits of the current study, SD282 arrested periodontal disease progression, thus highlighting the therapeutic potential of this novel class of inhibitors.
Dose‐Dependent Effects of Platelet Gel Releasate on Activities of Human Osteoblasts
Authors: Uggeri Jacopo , Belletti Silvana , Guizzardi Stefano , Poli Tito , Cantarelli Stefano , Scandroglio Renato , Gatti Rita
Published: October 2007

Background: Platelet‐rich plasma is used in oral and maxillofacial surgery; however, its real efficacy is debated. Also, the in vitro effects on bone‐specific functions are contradictory. Understanding the mechanisms of action of platelet‐derived factors could be the basis for their proper use in clinical applications.

Methods: The functional parameters of osteoblasts (proliferation, alkaline phosphatase, collagen synthesis, and calcium deposition) were analyzed in vitro for 14 days in the presence of different concentrations (100%, 33%, and 11%) of platelet gel releasate (PGR).

Results: Concentrations of 100% PGR and 33% PGR stimulated cells to proliferate more than 10% fetal calf serum. The effect on cell proliferation was dose dependent, and the addition of dexamethasone (dex) and β‐glycerophosphate (β‐GP) reduced the proliferative effects. Alkaline phosphatase activity was stimulated by 33% PGR and 11% PGR after 7 days and was induced further by dex and β‐GP. Also, collagen synthesis, measured on day 11, was stimulated by 33% PGR and 11% PGR. Calcium deposition, evaluated after 7 and 14 days, was greatest in cells treated with PGR supplemented with dex and GP. The mineralization process increased with time; on day 14, calcium aggregates were observed in all cultures treated with PGR (100%, 33%, and 11%).

Conclusions: PGR stimulated osteoblast proliferation in a dose dependent manner and, when used at 33% and 11%, induced maximum levels of alkaline phosphatase and collagen synthesis. Moreover, in the presence of dex and β‐GP, PGR stimulated the end maturative status of cells as expressed by the deposition of calcium nodules.
Effect of Rinsing With an Essential Oil–Containing Mouthrinse on Subgingival Periodontopathogens
Authors: Fine Daniel H. , Markowitz Kenneth , Furgang David , Goldsmith Deborah , Ricci‐Nittel Danette , Charles Christine H. , Peng Penny , Lynch Michael C.
Published: October 2007

Background: Studies have shown that the nature and amount of supragingival plaque can influence the composition of the contiguous subgingival flora. The purpose of this study was to investigate the effect of rinsing with an essential oil antimicrobial mouthrinse on levels of representative subgingival bacteria in subjects with mild to moderate periodontitis.

Methods: This controlled study used a randomized, double‐masked, 2 × 2 crossover design. After baseline subgingival sampling, 37 qualifying subjects rinsed with the essential oil mouthrinse or a negative control twice daily for 14 days, with a post‐treatment sample obtained on day 15. Following a washout period, the procedure was repeated with the alternative rinse. Target organisms enumerated were Porphyromonas gingivalis, Fusobacterium nucleatum, Veillonella sp., and total anaerobes. Intergroup comparisons of post‐treatment log‐transformed colony forming unit counts were made using analysis of covariance.

Results: After 14 days of twice‐daily rinsing, the level of each of the target subgingival organisms was significantly lower in the essential oil group than in the control group (P <0.001), with percent reductions ranging from 66.3% to 79.2%.

Conclusions: Rinsing with the essential oil antiplaque/antigingivitis mouthrinse can have significant antimicrobial activity against subgingival periodontopathogens. Most likely, the antimicrobial effect was mediated primarily by disruption of the contiguous supragingival plaque by the mouthrinse. Because studies have shown that control of supragingival plaque can influence the onset and/or progression of periodontitis, additional studies on non‐prescription antimicrobial oral care products may lead to new regimens for decreasing the burden of periodontal diseases in the population.
GCF MMP‐8 Levels in Smokers and Non‐Smokers With Chronic Periodontitis Following Scaling and Root Planing Accompanied by Systemic Use of Flurbiprofen
Authors: Kurtis Bülent , Tüter Gülay , Serdar Muhittin , Pinar Selin , Demirel Ilkim , Toyman Utku
Published: October 2007

Background: Cigarette smoking has been identified as an important risk factor for the initiation and progression of chronic periodontitis (CP). The aim of this study was to investigate the effects of phase I periodontal therapy and adjunctive flurbiprofen administration on matrix metalloproteinase (MMP)‐8 levels in gingival crevicular fluid (GCF) samples from smoking and non‐smoking patients with CP.

Methods: Twenty‐nine non‐smoking and 29 smoking patients with CP were divided into four groups according to periodontal treatment modalities. Group 1 (non‐smokers with CP) and group 3 (smokers with CP) patients received daily 100‐mg flurbiprofen tablets in a 2 × 1 regimen for 10 days together with scaling and root planing (SRP). Patients in group 2 (non‐smokers with CP) and group 4 (smokers with CP) received placebo tablets in a 2 × 1 regimen for 10 days together with SRP. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) measurements were recorded; GCF samples were collected from each sampling area at baseline and after the 10‐day period of drug intake by a single examiner who was unaware of the treatment modality. Assays for GCF MMP‐8 were carried out by an enzyme‐linked immunosorbent assay.

Results: All groups showed statistically significant reductions in PI and GI scores following the phase I periodontal treatment (P <0.05), but no statistical differences were observed in PD and CAL scores after therapy. In all groups, the reduction of GCF MMP‐8 levels after therapy was statistically significant compared to baseline levels (P <0.001). When groups 1 and 3 and 2 and 4 were compared according to GCF MMP‐8 levels after the therapy, no statistically significant differences were observed (P = 0.117 and P = 0.485, respectively).

Conclusion: Flurbiprofen administration had no additional inhibitory effect over SRP alone on GCF levels of MMP‐8 in smokers compared to non‐smokers with CP.
Mapping Clay Content across Boundaries at the Landscape Scale with Electromagnetic Induction
Authors: Weller U. , Zipprich M. , Sommer M. , Castell W. Zu , Wehrhan M.
Published: October 2007

Detailed information on soil textural heterogeneity is essential for land management and conservation. It is well known that in individual fields, measurement of the soil's apparent electrical conductivity (ECa) offers an opportunity to map the clay content of soils with free drainage under a humid climate. At the catchment scale, however, units of different land management and differing sampling dates add variation to ECa and constrain the mapping across field boundaries. We analyzed their influence and compared three approaches for applying electromagnetic induction (EMv) to clay‐content mapping at the landscape scale across the boundaries of individual fields and different sampling dates. In the study region, a separate calibration of the relation between clay and ECa for each field and sampling date (fieldwise calibration) yielded satisfactory clay‐content predictions only if the costly precondition of sufficient calibration points for each field was fulfilled. We propose a method (nearest‐neighbors ECa correction) for unifying ECa across boundaries based only on the ECa data themselves, and the assumption of continuity of textural properties at field boundaries, which was fulfilled in the landscape studied. Prediction is calibrated once for the entire landscape, which allows a reduced set of calibration points. The coefficient of determination for predicting clay content (here, including silt <4 μm) was improved from R2 = 0.66 (no correction for land use and sampling date) to R2 = 0.85 (n = 46). With the method developed, ECa offers a powerful and cheap method of clay‐content mapping in agricultural landscapes.
Soil and Plant Indices for Predicting Eucalypt Response to Nitrogen in Uruguay
Authors: Perdomo Carlos , Durán José , Llovet Pablo
Published: October 2007

Eucalypt plantations have been increasingly fertilized with N applied postplanting in Uruguay, but information on the benefits of the practice is scarce. The objective of this study was to identify the N availability indices (NAI) able to differentiate responsive from unresponsive sites when N was applied to eucalypts 6 or 12 mo after planting (MAP). The NAI were based on soil and plant analyses. Volume yield response to N was evaluated in 20 experiments conducted in plantations ofEucalyptus globulusLabille andE. grandisHill ex Maiden. The NAI were related to volume response expressions by using linear and quadratic‐plateau models, and the model with the highestR2was selected. Leaf N concentration (LNC) was the NAI most strongly related to N response in bothE. grandisfertilized at 6 MAP (seven sites) andE. globulusfertilized at 12 MAP (six sites) and the estimated critical levels were 34.6 and 20.9 g kg−1, respectively. None of the NAI could be selected in theE. globulussites fertilized at 6 MAP, but soil mineralizable N (NMIN) was clearly related to N response when allE. globulussites were pooled (12 sites), resulting in a critical level of 109 mg N kg−1Although theR2of the models describing relationships between the selected NAI and N response varied from 0.52 to 0.94, most NAI separated responsive from unresponsive sites. The results suggest that LNC and NMIN can be used as tools to improve prediction of the early eucalypt volume response to N in Uruguay.
On the Use of Linearized Langmuir Equations
Authors: Bolster Carl H. , Hornberger George M.
Published: October 2007

One of the most commonly used models for describing solute sorption to soils is the Langmuir model. Because the Langmuir model is nonlinear, fitting the model to sorption data requires that the model be solved iteratively using an optimization program. To avoid the use of optimization programs, a linearized version of the Langmuir model is often used so that model parameters can be obtained by linear regression. Although the linear and nonlinear Langmuir equations are mathematically equivalent, there are several limitations to using linearized Langmuir equations. We examined the limitations of using linearized Langmuir equations by fitting P sorption data collected on eight different soils with four linearized versions of the Langmuir equation and comparing goodness‐of‐fit measures and fitted parameter values with those obtained with the nonlinear Langmuir equation. We then fit the sorption data with two modified versions of the Langmuir model and assessed whether the fits were statistically superior to the original Langmuir equation. Our results demonstrate that the use of linearized Langmuir equations needlessly limits the ability to model sorption data with good accuracy. To encourage the testing of additional nonlinear sorption models, we have made available an easily used Microsoft Excel spreadsheet (ars.usda.gov/msa/awmru/bolster/Sorption_spreadsheets) capable of generating best‐fit parameters and their standard errors and confidence intervals, correlations between fitted parameters, and goodness‐of‐fit measures. The results of our study should promote more critical evaluation of model fits to sorption data and encourage the testing of more sophisticated sorption models.
Long‐Term Tillage and Cropping Sequence Effects on Dryland Residue and Soil Carbon Fractions
Authors: Sainju Upendra M. , Caesar-TonThat Thecan , Lenssen Andrew W. , Evans Robert G. , Kolberg Robert
Published: October 2007

Long‐term management practices are needed to increase dryland C storage and improve soil quality. We evaluated the 21‐yr effects of combinations of tillage and cropping sequences on dryland crop biomass (stems + leaves) returned to the soil, residue C, and soil C fractions at the 0‐ to 20‐cm depth in a Dooley sandy loam (fine‐loamy, mixed, frigid, Typic Argiborolls) in eastern Montana. Treatments were no‐till continuous spring wheat (Triticum aestivum L.) (NTCW), spring‐tilled continuous spring wheat (STCW), fall‐ and spring‐tilled continuous spring wheat (FSTCW), fall‐ and spring‐tilled spring wheat–barley (Hordeum vulgare L.) (1984–1999) followed by spring wheat–pea (Pisum sativum L.) (2000–2004) (FSTW‐B/P), and spring‐tilled spring wheat–fallow (STW‐F). Carbon fractions were soil organic C (SOC), soil inorganic C (SIC), particulate organic C (POC), microbial biomass C (MBC), and potential C mineralization (PCM). Mean crop biomass was 53 to 66% greater in NTCW, STCW, FSTCW, and FSTW‐B/P than in STW‐F. Soil surface residue amount and C content in 2004 were 46 to 60% greater in NTCW and FSTCW than in STW‐F. As a result, soil C fractions at 0 to 20 cm were 23 to 141% greater in all other treatments than in STW‐F due to increased C input. At 0 to 5 cm, SOC, SIC, POC, and PCM were greater in NTCW than in FSTW‐B/P. At 5 to 20 cm, POC was greater in NTCW than in FSTW‐B/P and PCM was greater in STCW than in FSTCW. Long‐term reduced tillage with continuous nonlegume cropping increased dryland crop biomass, residue and soil C storage, and soil quality by increasing microbial biomass and activities compared with a conventional system such as STW‐F.
Defective Lipid Delivery Modulates Glucose Tolerance and Metabolic Response to Diet in Apolipoprotein E–Deficient Mice
Authors: Hofmann Susanna M. , Perez-Tilve Diego , Greer Todd M. , Coburn Beth A. , Grant Erin , Basford Joshua E. , Tschöp Matthias H. , Hui David Y.
Published: October 2007

OBJECTIVE—Apolipoprotein E (ApoE) regulates plasma lipid levels via modulation of lipolysis and serving as ligand for receptor-mediated clearance of triglyceride (TG)-rich lipoproteins. This study tested the impact of modulating lipid delivery to tissues on insulin responsiveness and diet-induced obesity.

RESEARCH DESIGN AND METHODS—ApoE+/+ and apoE−/− mice were placed on high-fat–high-sucrose diabetogenic diet or control diet for 24 weeks. Plasma TG clearance, glucose tolerance, and tissue uptake of dietary fat and glucose were assessed.

RESULTS—Plasma TG clearance and lipid uptake by adipose tissue were impaired, whereas glucose tolerance was improved in control diet–fed apoE−/− mice compared with apoE+/+ mice after an oral lipid load. Fat mass was reduced in apoE−/− mice compared with apoE+/+ mice under both dietary conditions. The apoE−/− mice exhibited lower body weight and insulin levels than apoE+/+ mice when fed the diabetogenic diet. Glucose tolerance and uptake by muscle and brown adipose tissue (BAT) was also improved in mice lacking apoE when fed the diabetogenic diet. Indirect calorimetry studies detected no difference in energy expenditure and respiratory quotient between apoE+/+ and apoE−/− mice on control diet. Energy expenditure and uncoupling protein-1 expression in BAT were slightly but not significantly increased in apoE−/− mice on diabetogenic diet.

CONCLUSIONS—These results demonstrated that decreased lipid delivery to insulin-sensitive tissues improves insulin sensitivity and ameliorates diet-induced obesity.
Comparison of the Effects of Pioglitazone and Metformin on Hepatic and Extra-Hepatic Insulin Action in People With Type 2 Diabetes
Authors: Basu Rita , Shah Pankaj , Basu Ananda , Norby Barbara , Dicke Betty , Chandramouli Visvanathan , Cohen Ohad , Landau Bernard R. , Rizza Robert A.
Published: October 2007

OBJECTIVE—To determine mechanisms by which pioglitazone and metformin effect hepatic and extra-hepatic insulin action.

RESEARCH DESIGN AND METHODS—Thirty-one subjects with type 2 diabetes were randomly assigned to pioglitazone (45 mg) or metformin (2,000 mg) for 4 months.

RESULTS—Glucose was clamped before and after therapy at ∼5 mmol/l, insulin raised to ∼180 pmol/l, C-peptide suppressed with somatostatin, glucagon replaced at ∼75 pg/ml, and glycerol maintained at ∼200 mmol/l to ensure comparable and equal portal concentrations on all occasions. Insulin-induced stimulation of glucose disappearance did not differ before and after treatment with either pioglitazone (23 ± 3 vs. 24 ± 2 μmol · kg−1 · min−1) or metformin (22 ± 2 vs. 24 ± 3 μmol · kg−1 · min−1). In contrast, pioglitazone enhanced (P < 0.01) insulin-induced suppression of both glucose production (6.0 ± 1.0 vs. 0.2 ± 1.6 μmol · kg−1 · min−1) and gluconeogenesis (n = 11; 4.5 ± 0.9 vs. 0.8 ± 1.2 μmol · kg−1 · min−1). Metformin did not alter either suppression of glucose production (5.8 ± 1.0 vs. 5.0 ± 0.8 μmol · kg−1 · min−1) or gluconeogenesis (n = 9; 3.7 ± 0.8 vs. 2.6 ± 0.7 μmol · kg−1 · min−1). Insulin-induced suppression of free fatty acids was greater (P < 0.05) after treatment with pioglitazone (0.14 ± 0.03 vs. 0.06 ± 0.01 mmol/l) but unchanged with metformin (0.12 ± 0.03 vs. 0.15 ± 0.07 mmol/l).

CONCLUSIONS—Thus, relative to metformin, pioglitazone improves hepatic insulin action in people with type 2 diabetes, partly by enhancing insulin-induced suppression of gluconeogenesis. On the other hand, both drugs have comparable effects on insulin-induced stimulation of glucose uptake.
Modulation of Ciliary Beat Frequency in the Upper Airway by Prostaglandins
Authors: Schlosser Rodney J. , Franco Ramon A. , Czaja Judith M. , McCaffrey Thomas V.
Published: October 2007

Prostaglandins are ubiquitous within tissues and participate in several local regulatory functions. Previous reports have presented conflicting evidence on their role in ciliary activity in the upper airway. We studied the in vitro effects of prostaglandin E2 (PGE2) and a prostaglandin I2 analog (Iloprost) on the ciliary beat frequency (CBF) of human adenoid explants and rabbit sinus mucosa. Tissue explants were maintained in culture at 35°C. PGE2 or Iloprost was added to the culture media at concentrations of 10–6, to 10–12 M. CBF was determined using phase contrast microscopy and microphotometry. PGE2 increased CBF with a maximum increase of 54.6% in rabbit mucosa (P < 0.01) and 20.0% in human adenoid (P < 0.009). Iloprost increased CBF with a maximum increase of 35.2% in rabbit mucosa (P < 0.02) and 16.4% in human adenoid (P < 0.03). Induced production of endogenous prostaglandins was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac) prior to addition of PGE2 or Iloprost. Diclofenac had no effect on the ciliostimulatory effects of PGE2 (P > 0.36), however it significantly decreased the ciliostimulatory effect of Iloprost (P < 0.037). Both PGE2 and Iloprost stimulate ciliary motility, yet the action of PGE2 is direct, whereas Iloprost stimulates cilia by release of endogenous prostaglandins in both the human and rabbit.
Subjective and Objective Evaluation in Endoscopic Sinus Surgery
Authors: Ikeda Katsuhisa , Kondo Yoshifumi , Sunose Hiroshi , Hirano Koji , Oshima Takeshi , Shimomura Akira , Suzuki Hideaki , Takasaka Tomonori
Published: October 2007

Endoscopic sinus surgery (ESS) is the first modality for the surgical treatment of chronic sinusitis. We evaluated the outcome of ESS based on subjective and objective assessment. Subjective improvement was achieved in 98% of 54 patients chosen consecutively in the present study. The extent of disease revealed by computed tomographic (CT) scans was significantly ameliorated to an 82% improvement rate by ESS. However, no correlation of improvement rate between symptoms and CT scores was obtained. Both quantitative olfaction and anterior rhinomanometry were significantly improved following ESS. The present study provides objective evidence for clinical efficacy of ESS in the treatment of chronic sinusitis.
The Effects of Environmental Noise on Acoustic Rhinometry
Authors: Corey Jacquelynne P. , Gungor Anil , Nelson Robert H. , Velde Therese
Published: October 2007

Acoustic Rhinometry (AR) evaluates the geometry of the nasal cavity by means of acoustic reflections. Since it is a recently developed testing procedure, little is known about the various environmental factors that may affect measurements made with this technique. The acoustic signal generated from the source and received by the microphone(s) within the system are audible tones. The system is currently operated in ordinary office settings. Therefore, other noise present in the testing environment may interfere with test measurements. This study evaluates the effects of different sources of environmental noise on Acoustic Rhinometry measurements.
Cromolyn Sodium has no Significant Direct Effect on Nasal Mucosal Congestion or Histamine Sensitivity
Authors: Talving Peep , Backhaus Michael , Graf Peter , Hallén Hans C.
Published: October 2007

The mast cell stabilizing action of cromolyn sodium has long been known. This action reduces symptoms from exposure to allergen. Recent studies, however, also indicate a direct action of cromolyn sodium, which reduces symptoms even if cromolyn sodium is given after allergen exposure. The mechanisms are not yet fully understood. The aims of this study were to examine whether cromolyn sodium has a decongestive effect on the nasal mucosa and whether it reduces the histamine sensitivity of the nasal mucosa. Fourteen healthy volunteers took part in the trial. The study was designed as a double-blind cross-over study, in which the subjects were pretreated with placebo or cromolyn sodium 30 minutes before recording the nasal mucosa swelling and histamine sensitivity. The recordings were made with rhinostereometry. The results show that cromolyn sodium has no decongestive effect and that the mean histamine sensitivity is lower after cromolyn sodium pretreatment, but the difference is not significant.
Controlled Release and Absorption Resonance of Fluorescent Silica‐Coated Platinum Nanoparticles
Authors: Liu S. , Wong Y. , Wang Y. , Wang D. , Han M.‐Y.
Published: October 2007

Aggregation‐driven seeded growth of uniform platinum nanoparticles and exclusive silica‐coating of the as‐grown platinum nanoparticles have been achieved successfully. Fluorescent Pt@SiO2 nanoparticles have also been reproducibly prepared via effective co‐condensation of silanized dye molecules with tetraethylorthosilicate. The dye‐loaded Pt@SiO2 nanoparticles have been exploited as model carriers for thermal‐responsive controlled release of guest molecules via slow hydrolysis/dissolution of silica shells; importantly, the encapsulated platinum cores have also been used as nanoprobes to simultaneously investigate their controlled release process. Meanwhile, unique size‐sensitive absorbance resonance in the dye‐loaded Pt@SiO2 nanoparticles has been demonstrated for the first time, and it is expected to find novel application.
Preparation and Application of Novel Microspheres Possessing Autofluorescent Properties
Authors: Wei W. , Wang L.‐Y. , Yuan L. , Wei Q. , Yang X.‐D. , Su Z.‐G. , Ma G.‐H.
Published: October 2007

Fluorescent microspheres are widely used as biological tracers. In this study, uniformly sized chitosan microspheres crosslinked with glutaraldehyde (CG microspheres) and formaldehyde (CF microspheres) are successfully prepared by the Shirasu Porous Glass (SPG) membrane emulsification technique. Selectively reduced CG microspheres (SRCG microspheres) are obtained by NaBH4 reduction. These chitosan microspheres are found to exhibit fluorescent properties without conjugation to any fluorescent agent. The fluorescence color varies with different crosslinkers and can be modulated by further chemical reduction, whereas the fluorescence intensity can be controlled by tuning the particle size and degree of crosslinking. The autofluorescence of the microspheres is applied to study the phagocytosis of HepG2 cells using the microspheres as novel tracers. Quantitative and qualitative evaluations show that these chitosan microspheres serve as bright, inert, durable, and extremely photostable tracers.
Synthesis of Symmetrical Bisquinolones via Nickel(0)‐Catalyzed Homocoupling of 4‐Chloroquinolones
Authors: Hashim Jamshed , Kappe C. Oliver
Published: October 2007

A method for the gram‐scale preparation of functionalized 4,4′‐bisquinolones using a microwave‐assisted Ullmann‐type homocoupling reaction is described. The method is catalytic in nickel(0) which is generated in situ by reduction from an inexpensive nickel(II) source and utilizes readily available 4‐chloroquinolin‐2(1H)‐ones as starting materials. In contrast to the alternative palladium(0)‐catalyzed one‐pot borylation/Suzuki cross‐coupling reaction, the new method avoids the use of an expensive catalyst and cross‐coupling partner such as bis(pinacolato)diboron.
Selective Terminal Alkyne Metathesis: Synthesis and Use of a Unique Triple Bonded Dinuclear Tungsten Alkoxy Complex Containing a Hemilabile Ligand
Authors: Coutelier Olivier , Nowogrocki Guy , Paul Jean‐François , Mortreux André
Published: October 2007

The in situ synthesis of new alkyne metathesis catalysts is described, with particular emphasis on the search for tris‐alkoxytungsten‐based terminal alkyne metathesis. In that context, hemilabile, ether‐containing alkoxy ligands have proved to be suitable and have led to the design and use of a sterically hindered hemilable ligand for the synthesis of a well‐defined binuclear, triple‐bonded W≡W complex. This complex is shown to be a highly active and selective catalyst precursor for terminal alkyne metathesis, and allows the unprecedented metathesis of phenylacetylene.
Applicability Aspects of Transition Metal‐Catalyzed Aromatic Amination Protocols in Medicinal Chemistry
Authors: Tasler Stefan , Mies Jan , Lang Martin
Published: October 2007

The application of palladium‐ and copper‐catalyzed reactions for the aromatic amination of pharmacologically relevant scaffolds is investigated. The focus is set on the scope of several protocols for the introduction of amines of broad structural diversity, allowing for the synthesis of numerous derivatives of one biological hit structure for screening in biological assay systems. Thus, attaining optimized yields and TONs had not a major priority, most important were practical aspects, that is no further purification and drying of reagents and solvents had to be envisaged, ideally only a few transition metal‐based protocols had to be applied for synthesizing structurally diverse compounds in sufficient amounts (several milligrams) for screening without any fine‐tuning of conditions and catalytic systems.
Direct Arylation of Thiophenes via Palladium‐Catalysed CH Functionalisation at Low Catalyst Loadings
Authors: Battace Ahmed , Lemhadri Mhamed , Zair Touriya , Doucet Henri , Santelli Maurice
Published: October 2007

Palladium associated with cis,cis,cis‐1,2,3,4‐tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) was found to promote the direct 2‐arylation of a variety of thiophene derivatives via CH functionalisation in good yields using very low catalyst loadings. Electron‐deficient, electron‐excessive or sterically‐congested aryl bromides are tolerated. Moreover, several substituents on the aryl bromide or thiophene derivatives such as acetyl, formyl, nitrile, nitro, ester, methoxy, fluoro or trifluoromethyl are tolerated. The most reactive aryl bromides were coupled with thiophenes derivatives using as little as 0.1–0.01 mol % catalyst.
Efficient Activation of 2‐Iminomethylpyridine/Cobalt‐Based Alkyne [2+2+2] Cycloaddition Catalyst by Addition of a Silver Salt
Authors: Goswami Avijit , Ito Taichi , Okamoto Sentaro
Published: October 2007

The addition of silver triflate (AgOTf) or silver hexafluoroantimonate (AgSbF6) significantly increased the activity of the 2‐(arylimino)methylpyridine/cobalt(II) chloride hexahydrate (CoCl2⋅6 H2O)/zinc catalyst in alkyne cyclotrimerizations thereby accelerating the reaction and enabling the use of unactivated, simple internal alkynes as the monoyne substrate: The rate of reaction was found to be highly dependent on the nature of the counter anion (X−) and the ligand (L) in the postulated cationic cobalt(I) complex [LCo(I)]+X−.
Nanoheterogeneous Catalytic Hydrogenation of Arenes: Evaluation of the Surfactant‐Stabilized Aqueous Ruthenium(0) Colloidal Suspension
Authors: Nowicki Audrey , Le Boulaire Virginie , Roucoux Alain
Published: October 2007

The hydrogenation of various aromatic compounds by a surfactant‐stabilized aqueous ruthenium(0) colloidal suspension was investigated. The nanocatalysts in the size range of 2.5–3.5 nm were synthesized by reducing ruthenium trichloride salt with sodium borohydride and were stabilized by the highly water soluble N,N‐dimethyl‐N‐cetyl‐N‐(2‐hydroxyethyl)ammonium chloride salt according to our classical approach. The efficient catalytic reactions were performed at room temperature and under hydrogen pressure. The effect of the stirring, namely magnetic stir bar or gas projection impeller, was also studied. A comparison with an analogous rhodium nanocatalyst is described.
A Practical Transition Metal‐Free Aryl‐Aryl Coupling Method: Arynes as Key Intermediates
Authors: Leroux Frédéric R. , Bonnafoux Laurence , Heiss Christophe , Colobert Françoise , Lanfranchi Don Antoine
Published: October 2007

Upon treatment of various aryllithium intermediates with 1,2‐dibromobenzene or 1‐bromo‐2‐iodobenzene, dissymmetrical ortho,ortho′‐di‐, tri‐ and even tetrasubstituted bromo‐ or iodobiaryls become readily available. The crucial steps in all these reactions were the nucleophilic addition of the organolithium precursor to a transient aryne species released from it by β‐elimination of a lithium halide and, stabilization of the resulting 2‐biaryllithium intermediate by in situ transfer of bromine or iodine from the starting material. This straightforward transition metal‐free access to biaryls allows the preparation of highly valuable halobiaryls on a gram scale in excellent yields. These precursors can be subsequently functionalized by highly regioselective halogen/metal permutations into a vast variety of target molecules. This was demonstrated in the synthesis of several mono‐ and diphosphine ligands.
Copper‐Catalyzed Protodecarboxylation of Aromatic Carboxylic Acids
Authors: Gooßen Lukas J. , Thiel Werner R. , Rodríguez Nuria , Linder Christophe , Melzer Bettina
Published: October 2007

A catalyst generated from copper(I) oxide and 4,7‐diphenyl‐1,10‐phenanthroline for the first time allows the catalytic protodecarboxylation even of deactivated aromatic carboxylic acids, giving rise to the corresponding arenes. Based on DFT calculations, a reaction pathway is proposed that accurately reflects the experimental results, such as the observed reactivity order of the substrates.
Decreased incidence of acute graft‐versus‐host disease by continuous infusion of cyclosporine with a higher target blood level
Authors: Oshima Kumi , Kanda Yoshinobu , Nakasone Hideki , Arai Shunya , Nishimoto Nahoko , Sato Hiroyuki , Watanabe Takuro , Hosoya Noriko , Izutsu Koji , Asai Takashi , Hangaishi Akira , Motokura Toru , Chiba Shigeru , Kurokawa Mineo
Published: October 2007

Cyclosporine A (CsA) is the mainstay of pharmacologic prevention of acute graft‐versus‐host disease (GVHD). We previously reported that continuous infusion of CsA with a target blood level between 250 and 400 ng/ml significantly increased the incidence of acute GVHD compared to twice‐daily infusion with a target trough level between 150 and 300 ng/ml. Thus, we raised the target level of CsA continuous infusion to 450–550 ng/ml. We treated 33 patients with the higher target level (CsA500) and compared the efficacy and toxicity with those in the 33 historical control patients (CsA300 group). Other transplantation procedures were not changed. The patients' characteristics were equivalent. The average CsA concentration was adjusted around 500 ng/ml and the actual daily dose was maintained at the initial dose (CsA 3mg/kg/day). Toxicities were equivalently observed among the two groups. The incidence of grades II–IV acute GVHD was significantly lower in the CsA500 group (27 vs. 52%, P = 0.033). The target level of CsA was identified as an independent significant risk factor for grades II–IV acute GVHD (P = 0.039), adjusted for the presence of HLA mismatch. The incidence of chronic GVHD was also decreased in the CsA500 group (47 vs. 73%, P = 0.016). We conclude that the toxicity of the continuous CsA infusion with a target level of 450–550 ng/ml is acceptable and the efficacy to prevent acute GVHD is significant. A larger comparative study is warranted to confirm these findings. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
High prevalence of parkinsonian disorders associated to manganese exposure in the vicinities of ferroalloy industries
Authors: Lucchini Roberto G. , Albini Elisa , Benedetti Laura , Borghesi Stefano , Coccaglio Romana , Malara Eros C. , Parrinello Giovanni , Garattini Siria , Resola Sergio , Alessio Lorenzo
Published: October 2007

Objective

To assess the prevalence of Parkinsonian disturbances in relationship to environmental exposure to manganese due to ferroalloy industries in the province of Brescia, Northern Italy.

Methods

Manganese concentrations were measured in settled dust collected in each of the 206 municipalities. Parkinsonian patients were identified using two sources: (1) clinical registers from local hospitals, specialized neurologists, and exemption from prescription payment; (2) L‐Dopa prescriptions. Standardized prevalence rates and raw and full Bayesian‐smoothed standardized morbidity ratios (SMRs) were calculated for the entire province and for each municipality.

Results

Manganese concentrations in settled dust were significantly higher in the surroundings and downwind from the industrial plants. A total number of 2,677 Parkinsonian cases were identified among 903,997 residents (crude prevalence, 296/100,000; 95% CI: 284.80–307.20; standardized prevalence, 407/100,000; 95% CI: 393.87–420.12). Significantly higher SMRs (Kruskal–Wallis χ21 df = 17.55,P < 0.001) were observed in 37 municipalities in the vicinities of ferromanganese plants (324 cases among 77,708 residents; standardized prevalence 492/100,000; 95% CI: 442.80–541.20), compared to the other 169 municipalities of the province (2,353 cases among 826,289 residents, standardized prevalence 321/100,000; 95% CI 308.80–333.20). Row and Bayesian SMRs were associated with the concentrations of manganese in settled dust.

Conclusion

Study results suggest that environmental exposure to manganese is associated with an increased prevalence of Parkinsonian disturbances. Since the highest prevalence rates were observed in a closed community of the pre‐Alps where the industries are located, further research should address a possible interactive role of genetic factors. Am. J. Ind. Med. 50:788–800, 2007. © 2007 Wiley‐Liss, Inc.
Cross‐shift peak expiratory flow changes are unassociated with respirable coal dust exposure among South African coal miners
Authors: Naidoo Rajen N. , Robins Thomas G. , Becklake Margaret , Seixas Noah , Thompson Mary Lou
Published: October 2007

Background

The objectives of this study were to determine whether cross‐shift changes in peak expiratory flow rate (PEFR) were related to respirable dust exposure in South African coalminers.

Methods

Fifty workers were randomly selected from a cohort of 684 miners from 3 bituminous coalmines in Mpumalanga, South Africa. Peak expiratory efforts were measured prior to the commencement of the shift, and at the end of the shift on at least two occasions separated by at least 2 weeks, with full shift personal dust sampling being conducted on each occasion for each participant. Interviews were conducted, work histories were obtained and cumulative exposure estimates were constructed. Regression models examined the associations of cross‐shift changes in PEFR with current and cumulative exposure, controlling for shift, smoking and past history of tuberculosis.

Results

There were marginal differences in cross‐shift PEFR (ranging from 0.1 to 2 L/min). Linear regression analyses showed no association between cross‐shift change in PEFR and current or cumulative exposure. The specific shift worked by participants in the study showed no effect.

Conclusions

Our study showed no association between current respirable dust exposure and cross‐shift changes in PEFR. There was a non‐significant protective effect of cumulative dust exposure on the outcome, suggesting the presence of a “healthy worker survivor effect” in this data. Am. J. Ind. Med. 50:992–998, 2007. © 2007 Wiley‐Liss, Inc.
From lead to manganese through mercury: Mythology, science, and lessons for prevention
Authors: Alessio Lorenzo , Campagna Marcello , Lucchini Roberto
Published: October 2007

Background

Lead (Pb), mercury (Hg), and manganese (Mn) are well‐known neurotoxic metals. The knowledge of toxicity was developed through an extensive amount of research, starting with lead and mercury and proceeding today with manganese. Unfortunately, the consequent implementation of preventive measures was generally delayed, causing important negative effects to the exposed populations.

Methods

A review and historical reconstruction of the research development that yielded modern understanding of lead and mercury neurotoxicity was conducted to derive useful lessons for the prevention of manganese neurotoxicity.

Results

Medieval alchemists named planets and metals from gods since they were already aware of the toxicity and the adverse effects caused by lead and mercury. Historical lessons learned from these two metals may help to avoid the repetition of further mistakes regarding other neurotoxic metals like manganese. The knowledge and experience on the toxicokinetics and toxikodinamics of lead and mercury is useful and valuable to identify a proper approach to “safe” exposure levels for manganese.

Conclusions

Further information is still needed on the early neurotoxic and neurobehavioral effects after prolonged exposure to very low doses of lead, mercury, and manganese. Nevertheless, according to the precautionary principle, effective preventive measures should be already undertaken to prevent the onset of more severe health effects in the population. This is the most important lesson to be learned and applied from more than 30 years of occupational and environmental neurotoxicology of metals. Am. J. Ind. Med. 50:779–787, 2007. © 2007 Wiley‐Liss, Inc.
ADH7 variation modulates extraversion and conscientiousness in substance‐dependent subjects
Authors: Luo Xingguang , Kranzler Henry R. , Zuo Lingjun , Zhang Huiping , Wang Shuang , Gelernter Joel
Published: October 2007

Human personality traits have been closely linked to substance dependence (SD), and are partially genetically determined. Recently, associations between alcohol dehydrogenase 7 (ADH7) and SD have been reported, which led us to investigate the relationship between ADH7 variation and personality traits. We assessed dimensions of the five‐factor model of personality and genotyped 4 ADH7 markers and 38 unlinked ancestry‐informative markers in 244 subjects with SD [178 European‐Americans (EAs) and 66 African‐Americans (AAs)] and 293 healthy subjects (253 EAs and 40 AAs). The relationships between ADH7 markers and personality traits were comprehensively examined using multivariate analysis of covariance (MANCOVA), and then decomposed by Roy Bargmann Stepdown analysis of covariance (ANCOVA). Generally, older individuals, AAs, and males had significantly lower personality scores (4.7 × 10−5 ≤ P ≤ 0.032), as reported previously. In SD subjects, Extraversion was most significantly associated with ADH7 haplotypes (3.7 × 10−4 ≤ P ≤ 0.001), diplotypes (0.007 ≤ P ≤ 0.012), and genotypes (P = 0.001), followed by Conscientiousness (0.005 ≤ P ≤ 0.033). The contributory haplotype and diplotypes contained the alleles and genotypes of rs284786 (SNP1) and rs1154470 (SNP4). In healthy subjects, other personality factors (except Extraversion) were associated with ADH7 diplotypes (0.005 ≤ P ≤ 0.016) and genotypes (0.002 ≤ P ≤ 0.052). Some of the gene effects on personality factors were modified by sex. The present study demonstrated that the ADH7 variation may contribute to the genetic component of variation in personality traits, with the risk for SD and personality traits being partially shared. © 2007 Wiley‐Liss, Inc.
The functional polymorphism of the hemoglobin‐binding protein haptoglobin influences susceptibility to idiopathic Parkinson's disease
Authors: Costa‐Mallen Paola , Checkoway Harvey , Zabeti Aram , Edenfield Michael J. , Swanson Phillip D. , Longstreth W.T. , Franklin Gary M. , Smith‐Weller Terri , Sadrzadeh Sayed M.H.
Published: October 2007

Oxidative stress and iron have been widely implicated in the etiology of Parkinson's disease (PD). Hemoglobin is the richest source of iron in the body. The human Haptoglobin (Hp) protein is a plasma alpha‐2 glycoprotein that removes free Hemoglobin from the circulation and tissues and is important in protection from oxidative stress, in immune system regulation, and angiogenesis. A common genetic polymorphism of Hp exists in the population, where the Hp 1‐1, Hp 2‐1, and Hp 2‐2 forms exhibit profound functional differences. In this study, the Hp genotype corresponding to phenotypes Hp 1‐1, 2‐1 and 2‐2 was determined in 312 idiopathic PD patients and 420 normal control subjects. A significant increase in the number of subjects carrying the Hp 2‐1 genotype was present among PD patients. The distribution of Hp genotypes among PD patients (16.0% Hp 1‐1, 56.4% Hp 2‐1, 27.6% Hp 2‐2) was significantly different from the distribution in controls (15.2% Hp 1‐1, 48.1% Hp 2‐1, 36.7% Hp 2‐2) (χ2 = 6.99, P = 0.030). The odds ratios for PD risk for Hp 2‐1 and Hp 1‐1 versus Hp 2‐2 genotype were 1.51 (1.07–2.12) and 1.36 (0.86–2.15), respectively. Overall, the association of Hp‐1 allele with PD resulted stronger among subjects who were never‐smokers as compared to ever‐smokers. Also, among ever‐smokers, Hp genotypes were significantly associated with PD only among women, but not men, indicating the presence of a gene × gender × smoking interaction. To our knowledge, this is the first study that investigates the association of Hp genotypes with the risk of PD. © 2007 Wiley‐Liss, Inc.
Genetic Association of Neurotrophic Tyrosine Kinase Receptor Type 2 (NTRK2) With Alzheimer's Disease
Authors: Chen Zuomin , Simmons Micah S. , Perry Rodney T. , Wiener Howard W. , Harrell Lindy E. , Go Rodney C.P.
Published: October 2007

Brain‐derived neurotrophic factor (BDNF)/tyrosine receptor kinase (TRK) signaling pathway activates a wide range of downstream intracellular cascades, regulating neuronal development and plasticity, long‐term potentiation, and apoptosis. The NTRK family encodes the receptors TRKA, TRKB, and TRKC, to which the neurotrophins, nerve growth factor (NGF), BDNF and neurotrophin‐3 (NT‐3) bind, respectively, with high affinity. Signaling through these receptors appears to be compromised in Alzheimer's disease (AD). This study is the most comprehensive investigation of genetic variants of NTRK2, and the first to show significant association between NTRK2 with AD. Fourteen single nucleotide polymorphisms (SNPs), located in 8 of 18 linkage disequilibrium (LD) blocks, were genotyped in 203 families with at least two AD affected siblings with mean age of onset (MAO) of 70.9 ± 7.4 years and one unaffected sibling from the NIMH‐ADGJ dataset. Family based association testing found no single SNP association, however, significant associations were found for two and three locus haplotypes (P = 0.012, P = 0.009, respectively) containing SNPs rsl624327, rsl443445, and rs378645. These SNPs are located in areas of the gene containing sequences that could be involved in alternative splicing and/or regulation of NTRK2. Our results suggest that NTRK2 may be a genetic susceptibility gene contributing to AD pathology. © 2007 Wiley‐Liss, Inc.