bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Curet and Paper Point Sampling of Subgingival Bacteria as Analyzed by Real‐Time Polymerase Chain Reaction
Authors: Jervøe‐Storm Pia‐Merete , AlAhdab Hazem , Koltzscher Max , Fimmers Rolf , Jepsen Søren
Published: April 2007

Background: The outcome of microbiological diagnostics may depend on the sampling technique. It was the aim of the present study to compare two widely used sampling techniques for subgingival bacteria using quantitative real‐time polymerase chain reaction.

Methods: Twenty patients with chronic periodontitis were randomized into two groups. In group A, samples were taken first with a paper point and then with a curet at the same site (single‐rooted teeth with probing depth >5 mm) before scaling and root planing and after 10 weeks. The sampling sequence was reversed in group B. The analysis enabled the quantification of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythensis and total bacterial counts (TBCs). Statistical analysis included t test, kappa, and Spearman correlation.

Results: Higher TBC was harvested with curets than by paper points (P = 0.008). The plaque composition with regard to total target pathogens was similar for both sampling techniques. A strong positive correlation was found between curet and paper point samples for TBC and single target bacteria.

Conclusions: Overall, there was a relatively good agreement for the results of paper point and curet sampling. Thus, both techniques seem to be suitable for microbiological diagnostics.
The r40‐kDa Outer Membrane Protein Human Monoclonal Antibody Protects Against Porphyromonas gingivalis–Induced Bone Loss in Rats
Authors: Hamada Nobushiro , Watanabe Kiyoko , Tahara Tomoyuki , Nakazawa Kumiko , Ishida Isao , Shibata Yasuko , Kobayashi Tetsuo , Yoshie Hiromasa , Abiko Yoshimitsu , Umemoto Toshio
Published: April 2007

Background: Porphyromonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. We recently reported the construction and characterization of human immunoglobulin G isotype clones, which were specifically reactive with recombinant (r) 40‐kDa outer membrane protein (OMP) of P. gingivalis. The aim of this study was to investigate the efficacy of human monoclonal antibody (hMAb) against r40‐kDa OMP of P. gingivalis to the protection alveolar bone loss by P. gingivalis in rats.

Methods: The role of 40‐kDa OMP in the adherence of P. gingivalis to human gingival epithelial cells (HGECs) was examined by preincubating with r40‐kDa OMP hMAb before adding the HGECs. Moreover, we used a rat model to examine the effect of the anti–r40‐kDa OMP hMAb in alveolar bone loss by oral infection. Forty‐six days after the last infection, the periodontal bone level was assessed morphometrically on defleshed rat jaws.

Results: The adherence to HGECs was reduced by 84% compared to adherence levels without the antibody. P. gingivalis could not be detected from rats in a P. gingivalis–non‐infected group and a group that was administered the anti–r40‐kDa OMP hMAb. The bone loss in P. gingivalis–infected animals that were administered the anti–r40‐kDa OMP hMAb was significantly lower than that of P. gingivalis–infected rats.

Conclusions: Our results suggest that transchromosomic mouse‐derived hMAb against r40‐kDa OMP of P. gingivalis protects against periodontal bone loss. This newly constructed anti–r40‐kDa OMP hMAb was used to protect against periodontal diseases caused by P. gingivalis infection.
Drug Concentration in Inflamed Periodontal Tissues After Systemically Administered Azithromycin
Authors: Gomi Kazuhiro , Yashima Akihiro , Iino Fumiaki , Kanazashi Mikimoto , Nagano Takatoshi , Shibukawa Naoya , Ohshima Tomoko , Maeda Nobuko , Arai Takashi
Published: April 2007

Background: Azithromycin is an azalide antibiotic, effective against a wide range of oral bacteria including periodontopathic bacteria. Azithromycin is taken up by phagocytes and is released into inflamed tissue over time. The concentration of azithromycin in inflamed periodontal tissues over time has not been studied. In this study, we determined the azithromycin concentration in the gingiva and inflammatory connective tissue of the periodontal pocket in periodontal patients who had been administered azithromycin systemically. We also evaluated the clinical and microbiologic effects of azithromycin.

Methods: Thirty‐four patients with periodontitis were prescribed azithromycin 500 mg once daily for 3 days. During the 14‐day study, clinical parameters (probing depth, gingival index, bleeding on probing, and gingival crevicular fluid level) were recorded, subgingival plaque was collected for bacteriologic examination, and the azithromycin concentration in the tissues lining the periodontal pocket was measured by agar diffusion bioassay.

Results: Clinical parameters significantly improved after administration of azithromycin. The total number of cultivated bacteria also significantly decreased by day 4 but slightly increased after day 7. Sustained reduction in levels of six periodontopathic bacteria was not apparent until day 14. On day 7, the azithromycin concentration in the tissues lining the periodontal pockets was 50% of that on day 4, and on day 14 only 20%.

Conclusion: Azithromycin is detectable in inflamed periodontal tissues ≥14 days after systemic administration; it is associated with clinical and microbiologic improvement.
Vertical Crestal Bone Changes Around Implants Placed Into Fresh Extraction Sockets
Authors: Covani Ugo , Cornelini Roberto , Barone Antonio
Published: April 2007

Background: The aim of this study was to analyze bone healing and vertical bone remodeling for implants placed immediately after tooth removal without guided bone regeneration techniques.

Methods: Twenty patients received 20 implants immediately after the removal of 20 teeth. All implants were placed within the undamaged alveoli confines, and the cervical portion of each implant was positioned at coronal bone level. The distance from implant shoulder and bone crest was measured for each implant at four sites (mesial, buccal, distal, and palatal/lingual). No membranes or filling materials were used. Primary flap closure was performed in all clinical cases.

Results: All peri‐implant bone defects had healed completely 6 months after implant placement. The pattern of bone healing around the neck of the implants showed an absence of peri‐implant defects. The vertical distance between the implant shoulder and bone crest ranged from 0 to 2 mm.

Conclusions: The bone remodeling of implants placed in fresh extraction sockets showed a healing pattern with new bone apposition around the implant's neck and horizontal and vertical bone reabsorption. The vertical bone reabsorption, which has been observed at buccal sites, was not associated with any negative esthetic implications.
Longitudinal Study of the Association Between Smoking as a Periodontitis Risk and Salivary Biomarkers Related to Periodontitis
Authors: Kibayashi Miyuki , Tanaka Muneo , Nishida Nobuko , Kuboniwa Masae , Kataoka Kosuke , Nagata Hideki , Nakayama Kunio , Morimoto Kanehisa , Shizukuishi Satoshi
Published: April 2007

Background: Insufficient data exist regarding the long‐term influence of lifestyle factors including smoking on periodontal health. The objective of this study was to examine the prospective association between smoking and periodontal disease progression and the effects of smoking on salivary biomarkers related to periodontitis.

Methods: Probing depth (PD) was measured at health checkups of workers in 1999 and 2003; additionally, lifestyle information was obtained through a questionnaire. In 2003, 219 of 256 (86%) workers examined at baseline completed PD measurements; saliva samples were also collected. Change in PD was used for assessment of periodontitis progression when three or more sites displayed an increase of ≥2 mm over 4 years. Salivary biomarker levels were determined by real‐time polymerase chain reaction and enzyme assay. Statistical methods included bivariate and multivariate regression analyses.

Results: In the multiple logistic model, in which lifestyle‐related factors served as independent variables, significant variables were current smoking and hours of sleep; respective odds ratios were 2.3 and 2.1. Additionally, 38.5% of periodontal disease progression was attributable to current smoking. Moreover, pack‐years of smoking showed a dose–response relationship with disease progression. Levels of salivary markers including prostaglandin E2, lactoferrin, albumin, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were significantly lower in current smokers than in non‐current smokers. However, no meaningful differences in the proportions of six periodontal pathogens were observed between current and non‐current smokers.

Conclusions: Smoking exerted the greatest influence on periodontitis risk among lifestyle factors. Smoking may suppress the host‐defense system, which may promote periodontal disease progression.
1‐Tetradecanol Complex Reduces Progression of Porphyromonas gingivalis–Induced Experimental Periodontitis in Rabbits
Authors: Hasturk Hatice , Jones Victor L. , Andry Chris , Kantarci Alpdogan
Published: April 2007

Background: It has been recently shown that monounsaturated fatty acids inhibit endothelial activation and reduce tissue responsiveness to cytokines. The present study has been planned to investigate topical application of a novel monounsaturated fatty acid complex (1‐tetradecanol complex) for prevention of Porphyromonas gingivalis–induced periodontitis in rabbits.

Methods: Experimental periodontitis was induced in New Zealand white rabbits with silk sutures tied around the mandibular second premolars bilaterally, followed by the topical application of 109 colony forming units (CFU) of P. gingivalis. 1‐Tetradecanol complex (1‐TDC) was topically applied at 1‐ and 10‐mg/ml concentrations in five animals in each group, whereas control animals received olive oil vehicle (five animals) three times per week for 6 weeks. Negative controls included ligature alone (14 animals) or ligature + P. gingivalis (non‐treatment; 15 animals). Rabbits were sacrificed after 6 weeks, and mandibular block sections were obtained; tissues were decalcified and embedded in paraffin. Thin sections (5 μm) were stained with hematoxylin and eosin or tartrate‐resistant acid phosphatase. Macroscopic and histologic evaluation of samples was followed by the characterization of cellular inflammatory infiltrate and quantitative histomorphometric measurements.

Results: Treatment with both concentrations of 1‐TDC and vehicle resulted in significant prevention of macroscopic periodontal inflammation and bone loss (75%; P <0.05) compared to the non‐treatment (ligature + P. gingivalis) group, where significant periodontal tissue destruction characterized by attachment and bone loss was detected. However, there was no statistically significant difference between the vehicle and both 1‐TDC groups. Histologically, 1‐TDC inhibited inflammatory cell infiltration and prevented osteoclastogenesis, whereas treatment with vehicle did not show the same effect as in the 1‐TDC groups; the difference between vehicle and the higher concentration of 1‐TDC (10 mg/ml) was statistically significant.

Conclusion: Topical application of an esterified monounsaturated fatty acid complex (1‐TDC) was found promising in preventing bone loss, inflammatory cell infiltration, and connective tissue destruction in the rabbit periodontitis model.
Periodontal Destruction Is Associated With Coronary Artery Disease and Periodontal Infection With Acute Coronary Syndrome
Authors: Gotsman Israel , Lotan Chaim , Soskolne W. Aubrey , Rassovsky Simona , Pugatsch Thea , Lapidus Ludmila , Novikov Yelena , Masrawa Siham , Stabholz Ayala
Published: April 2007

Background: Coronary artery disease (CAD) is a highly prevalent disease with significant morbidity and mortality. Periodontal disease has been suggested to influence this disease and has been associated with CAD in some epidemiologic studies. However, this relation is still controversial. This study aimed to determine the relationship between periodontal disease measures and CAD and acute coronary syndromes (ACSs).

Methods: Two hundred one patients presenting with stable angina or ACS referred for coronary angiography underwent a periodontal assessment including evaluation of periodontal pathogens. Severity of CAD was determined by the number of obstructed coronary arteries.

Results: Patients with severe CAD defined by multiple vessel disease had significantly more periodontal destruction than those with mild CAD, as shown by mean clinical attachment level, a measure of chronic periodontal disease (CAL; 5.43 ± 1.8 versus 4.85 ± 1.6; P = 0.02), percentage of teeth with CAL ≥5 mm (82.1 ± 23.4 versus 70.4 ± 26.9; P = 0.002), and number of missing teeth (8.75 ± 6.6 versus 6.76 ± 6.6; P = 0.03). Logistic regression analysis showed that percentage of teeth with CAL ≥5 mm was significantly associated with CAD severity. Patients with ACS had significantly higher plaque scores, gingival index, and Porphyromonas gingivalis counts than stable patients. Logistic regression analysis showed that either plaque score or percentage of P. gingivalis was significantly associated with ACS.

Conclusion: Periodontal destruction measures are significantly correlated with CAD severity, whereas periodontal infectious measures are significantly associated with clinical cardiac status.
Cortical Bone Thickness in Dentate and Edentulous Human Cadavers
Authors: Katranji Amar , Misch Kelly , Wang Hom‐Lay
Published: April 2007

Background: A critical component of treatment planning in dental implant therapy is the amount of available bone. Thick cortical plates have been the primary way to achieve primary implant stability. However, information about cortical bone thickness in various regions of the maxilla and mandible is largely missing. Hence, it was the purpose of this cadaver study to determine an average cortical bone thickness in different tooth locations.

Methods: To determine the average thickness of buccal and lingual plates, 28 cadaver heads (68% male and 32% female) with an average age of 73.1 years were measured at various locations correlating to molar (M), premolar (PM), and anterior (A) regions. Edentulous and dentate regions also were recorded.

Results: Average buccal cortical thicknesses were 1.69 mm (M), 1.43 mm (PM), and 1.04 mm (A) in the edentulous maxilla; 2.06 mm (M), 1.78 mm (PM), and 1.36 mm (A) in the edentulous mandible; 2.23 mm (M), 1.62 mm (PM), and 1.59 mm (A) in the dentate maxilla; and 1.98 mm (M), 1.20 mm (PM), and 0.99 mm (A) in the dentate mandible. Average lingual cortical thicknesses were 2.06 mm (M), 1.60 mm (PM), and 1.36 mm (A) in the edentulous maxilla; 2.39 mm (M), 1.88 mm (PM), and 1.66 mm (A) in the edentulous mandible; 2.35 mm (M), 2.0 mm (PM), and 1.95 mm (A) in the dentate maxilla; and 2.51 mm (M), 1.92 mm (PM), and 1.24 mm (A) in the dentate mandible.

Conclusions: The average cortical thickness of the buccal plates ranged from 1.0 to 2.1 mm in the edentulous maxilla and mandible, with the thinnest area in the anterior maxilla and the thickest area in the posterior mandible. The buccal plate of the dentate maxilla and mandible ranged from 1.6 to 2.2 mm in thickness, with the thinnest area in the lower anterior region and the thickest area in the upper posterior region.
Periodontal Services Rendered by General Practitioners
Authors: Lanning Sharon K. , Best Al M. , Hunt Ronald J.
Published: April 2007

Background: There are few reports in the dental literature regarding the types of periodontal services offered by general practitioners (GPs). The purpose of this study was to determine the specific nature of periodontal services rendered by GPs and to investigate whether certain variables affect GPs' practice patterns.

Methods: A 13‐item survey was mailed to a random sample of 600 dentists practicing in the state of Virginia. GPs were asked to identify the periodontal services rendered in their office within a 3‐month period. Descriptive statistics, simple correlation, and stepwise multiple regression analysis were used to identify significant relationships between variables and periodontal services.

Results: Ninety percent of GPs reported treating at least one patient with scaling and root planing, and 16% of GPs reported rendering this service to >36 patients. Eighty‐six percent of GPs reported providing periodontal maintenance in their practices. Approximately 50% of dentists reported up to 24 patients having received periodontal maintenance. Fifty‐eight percent of GPs reported that ≥90% of scaling and root planing was done by the hygienists. Fifty‐five percent of GPs treated at least one patient with site‐specific therapy using chemotherapeutic agents. Twenty‐eight percent of GPs treated one to five patients with low‐dose antibiotic. Seventy percent of GPs treated at least one patient with occlusal therapies, and 50% reported treating one to five patients with occlusal therapies. The most common surgical services performed included crown lengthening and pocket reduction surgery, which were done by 38% and 21% of GPs, respectively. A few GPs (N = 26) performed the majority of periodontal surgical services. Variables found to influence specific services rendered by GPs included year of dental school graduation, recent hours of continuing education related to periodontics, combined number of dental hygienist days per week, percentage of periodontal patients in practice, and referral for non‐surgical periodontal therapy.

Conclusions: A variety of periodontal services were offered by GPs. The most common services were non‐surgical in nature. Certain variables affected specific periodontal services rendered in general dental offices.
Effect of Systemically Administered Naproxen Sodium on Clinical Parameters and Myeloperoxidase and Elastase‐Like Activity Levels in Gingival Crevicular Fluid
Authors: Aras Hamit , Çağlayan Feriha , Güncü Güliz N. , Berberoğlu Atilla , Kılınç Kamer
Published: April 2007

Background: The present study was conducted to determine the possible effect of naproxen sodium on clinical status and the enzymatic profile of gingival crevicular fluid (GCF) when given as adjunct to periodontal treatment.

Methods: A total of 34 subjects with chronic periodontitis were selected and divided into two groups to receive either naproxen sodium or placebo. At baseline, GCF samples were obtained and probing depths (PD), gingival index (GI), plaque index (PI), and gingival bleeding index (GBI) scores were recorded. In the non‐steroidal anti‐inflammatory drug (NSAID) group, patients were treated with a protocol consisting of baseline periodontal treatment (scaling, root planing) and naproxen sodium (275 mg) administration daily for 6 weeks. In the placebo group, patients received the same treatment except placebo was given instead of naproxen sodium. At the end of the experimental period, clinical recordings and GCF sampling were repeated. Myeloperoxidase (MPO) and elastase‐like enzyme activity (ELA) levels were determined in GCF samples by a spectrophotometric method. GCF enzymatic content was calculated both as total enzyme activity and enzyme concentration.

Results: All of the clinical parameters, except mean GBI, were significantly lower in the experimental group (P <0.05). At baseline and at the end of the experimental period, there were no significant differences between the NSAID and placebo groups regarding GCF MPO and ELA levels in either mode of data presentation (P <0.05). However, in the NSAID group, mean ELA concentration (P = 0.002) and mean total ELA (P = 0.003) presented significant decreases with treatment. Also, with treatment, a general reduction in MPO levels was seen; however, this difference was not significant. Although constant and stable correlations between GCF enzyme levels and clinical parameters could not be found, positive and strong correlations were observed between total enzyme activity and enzyme concentrations.

Conclusion: Based on the positive clinical effect and the ELA profile of GCF, it can be suggested that NSAIDs given as an adjunct to baseline periodontal treatment could be beneficial in the outcome of treatment.
Systemic Expression of Heme Oxygenase-1 Ameliorates Type 1 Diabetes in NOD Mice
Authors: Hu Chien-Ming , Lin Heng-Huei , Chiang Ming-Tsai , Chang Pi-Fei , Chau Lee-Young
Published: April 2007

Heme oxygenase-1 (HO-1) is an enzyme with potent immunoregulatory capacity. To evaluate the effect of HO-1 on autoimmune diabetes, female NOD mice at 9 weeks of age received a single intravenous injection of a recombinant adeno-associated virus bearing HO-1 gene (AAV-HO-1; 0.5 × 1010-2.5 × 1010 viruses/mouse). In a dose-dependent manner, HO-1 transduction reduced destructive insulitis and the incidence of overt diabetes examined over a 15-week period. HO-1–mediated protection was associated with a lower type 1 T-helper cell (Th1)–mediated response. Adaptive transfer experiments in NOD.scid mice demonstrated that splenocytes isolated from AAV-HO-1–treated mice were less diabetogenic. Flow cytometry analysis revealed no significant difference in the percentages of CD4+CD25+ regulatory T-cells between saline-treated and AAV-HO-1–treated groups. However, the CD11c+ major histocompatibility complex II+ dendritic cell population was much lower in the AAV-HO-1–treated group. A similar protective effect against diabetes was observed in NOD mice subjected to carbon monoxide (CO) gas (250 ppm CO for 2 h, twice per week). These data suggest that HO-1 slows the progression to overt diabetes in pre-diabetic NOD mice by downregulating the phenotypic maturity of dendritic cells and Th1 effector function. CO appears to mediate at least partly the beneficial effect of HO-1 in this disease setting.
Characterization of Glucosensing Neuron Subpopulations in the Arcuate Nucleus
Authors: Fioramonti Xavier , Contié Sylvain , Song Zhentao , Routh Vanessa H. , Lorsignol Anne , Pénicaud Luc
Published: April 2007

Four types of responses to glucose changes have been described in the arcuate nucleus (ARC): excitation or inhibition by low glucose concentrations <5 mmol/l (glucose-excited and -inhibited neurons) and by high glucose concentrations >5 mmol/l (high glucose–excited and –inhibited neurons). However, the ability of the same ARC neuron to detect low and high glucose concentrations has never been investigated. Moreover, the mechanism involved in mediating glucose sensitivity in glucose-inhibited neurons and the neurotransmitter identity (neuropeptide Y [NPY] or pro-opio melanocortin [POMC]) of glucosensing neurons has remained controversial. Using patch-clamp recordings on acute mouse brain slices, successive extracellular glucose changes greater than and less than 5 mmol/l show that glucose-excited, high glucose–excited, glucose-inhibited, and high glucose–inhibited neurons are different glucosensing cell subpopulations. Glucose-inhibited neurons directly detect decreased glucose via closure of a chloride channel. Using transgenic NPY–green fluorescent protein (GFP) and POMC-GFP mice, we show that 40% of NPY neurons are glucose-inhibited neurons. In contrast, <5% of POMC neurons responded to changes in extracellular glucose >5 mmol/l. In vivo results confirm the lack of glucose sensitivity of POMC neurons. Taken together, hypo- and hyperglycemia are detected by distinct populations of glucosensing neurons, and POMC and NPY neurons are not solely responsible for ARC glucosensing.
Inhibiting Glycosphingolipid Synthesis Improves Glycemic Control and Insulin Sensitivity in Animal Models of Type 2 Diabetes
Authors: Zhao Hongmei , Przybylska Malgorzata , Wu I-Huan , Zhang Jinhua , Siegel Craig , Komarnitsky Svetlana , Yew Nelson S. , Cheng Seng H.
Published: April 2007

Previous reports have shown that glycosphingolipids can modulate the activity of the insulin receptor, and studies in transgenic mice suggest a link between altered levels of various gangliosides and the development of insulin resistance. Here, we show that an inhibitor of glycosphingolipid synthesis can improve glucose control and increase insulin sensitivity in two different diabetic animal models. In the Zucker diabetic fatty rat, the glucosylceramide synthase inhibitor (1R,2R)-nonanoic acid[2-(2′,3′-dihydro-benzo [1, 4] dioxin-6′-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]- amide-l-tartaric acid salt (Genz-123346) lowered glucose and A1C levels and improved glucose tolerance. Drug treatment also prevented the loss of pancreatic β-cell function normally observed in the Zucker diabetic fatty rat and preserved the ability of the animals to secrete insulin. In the diet-induced obese mouse, treatment with Genz-123346 normalized A1C levels and improved glucose tolerance. Analysis of the phosphorylation state of the insulin receptor and downstream effectors showed increased insulin signaling in the muscles of the treated Zucker diabetic fatty rats and diet-induced obese mice. These results suggest that inhibiting glycosphingolipid synthesis can significantly improve insulin sensitivity and glucose homeostasis and may therefore represent a novel therapeutic approach for the treatment of type 2 diabetes.
The Heterogeneity of Diabetes
Authors: Pietropaolo Massimo , Barinas-Mitchell Emma , Kuller Lewis H.
Published: April 2007

Diabetes is an emblematic example of a heterogeneous disease. Systemic inflammation has emerged as a prominent factor in the type 2 diabetes pathoetiology, but it remains ill-defined in type 1 diabetes. There is a wide spectrum of associations between inflammatory responses and diabetic syndromes. At one end of this spectrum, there is type 1 diabetes for which there is convincing evidence that chronic inflammation of pancreatic islets is a central aspect of disease pathogenesis. At the opposite end, is type 2 diabetes that is clearly associated with systemic inflammation, which could be either the cause or simply mark the underlying pathology. Accumulating evidence has substantiated that a subgroup of adult patients clinically diagnosed with type 2 diabetes exhibit autoantibody responses to islet autoantigens. The presence of these immunologic abnormalities is associated with a severe insulin secretory defect and the absence of signs of systemic inflammation as documented by plasma C-reactive protein and fibrinogen levels that are comparable with those of control populations. Islet autoantibody evaluation should be part of the diagnostic assessment for clinically diagnosed type 2 diabetes not only because it might predict the rate of progression to insulin requirement in adult populations but also to identify a pathogenically distinct disease phenotype characterized by the absence of systemic inflammation and its related disorders. A more appropriate characterization of this subgroup of clinically diagnosed type 2 diabetes, diabetes of autoimmune pathogenesis, will promote future research into the etiology, natural history, and treatment.
Association Studies of BMI and Type 2 Diabetes in the Neuropeptide Y Pathway
Authors: Campbell Catarina D. , Lyon Helen N. , Nemesh James , Drake Jared A. , Tuomi Tiinamaija , Gaudet Daniel , Zhu Xiaofeng , Cooper Richard S. , Ardlie Kristin G. , Groop Leif C. , Hirschhorn Joel N.
Published: April 2007

The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001–0.009, odds ratios [ORs] 1.27–1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 × 10−4, OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.
Involvement of Heat Shock Factor-1 in Glycated LDL–Induced Upregulation of Plasminogen Activator Inhibitor-1 in Vascular Endothelial Cells
Authors: Zhao Ruozhi , Shen Garry X.
Published: April 2007

Coronary artery disease is the predominant cause of death in diabetic patients. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of plasminogen activators. Heat shock protein (Hsp) was upregulated in uncontrolled diabetic patients. Our previous studies demonstrated that glycated LDL stimulated the generation of PAI-1 from vascular endothelial cells. The present study examined the effect of glycated LDL on the expression of heat shock factor-1 (HSF1), a physiological transcription factor of Hsp, and the involvement of HSF-1 in glycated LDL–induced production of PAI-1 in cultured human umbilical vein endothelial cells (HUVECs) and coronary artery endothelial cells (HCAECs). Treatment with glycated LDL increased the expression of HSF1 and Hsp-70 compared with LDL in subconfluent HCAECs or HUVECs, and that was associated with an increase of PAI-1 expression. The transfection of HSF1 gene enhanced the expression of PAI-1 in endothelial cells. Small interference RNA against HSF1 prevented glycated LDL–induced upregulation of PAI-1 in HCAECs or HUVECs. Glycated LDL increased the binding of a nuclear protein to the PAI-1 promoter. The nuclear protein–DNA complex was supershifted by HSF1 antibody. The presence of an antioxidant, butylated hydroxytulene, during the glycation of LDL prevented glycated LDL–induced increases of the expression of HSF1 or PAI-1 in endothelial cells. The results suggest that HSF-1 is involved in glycated LDL–induced upregulation of PAI-1 in subconfluent vascular endothelial cells through the binding of HSF1 to PAI-1 promoter. Glyco-oxidation may contribute to glycated LDL–induced expression of HSF1 and PAI-1 in endothelial cells.
Activation of Sphingosine Kinase-1 Mediates Inhibition of Vascular Smooth Muscle Cell Apoptosis by Hyperglycemia
Authors: You Bei , Ren Aixia , Yan Guijun , Sun Jianxin
Published: April 2007

Vascular smooth muscle cell (VSMC) apoptosis plays an essential role in vascular development and atherosclerosis. Hyperglycemia inhibits VSMC apoptosis, which may contribute to the development of diabetic vasculopathy. In the present study, we analyzed the mechanism of high-glucose–induced anti-apoptotic effect in cultured human aortic smooth muscle cells (HASMCs). Compared with normoglycemia, exposure of HASMCs to hyperglycemia but not mannitol significantly increased sphingosine kinase 1 (SK1) activity but not SK2 activity. This increase was inhibited by protein kinase C (PKC) inhibitor GF109203X, the antioxidant N-acetylcysteine, and the reduced form of glutathione. The mechanism of SK1 activation by high glucose involves plasma membrane translocation. In addition, hyperglycemia markedly inhibited serum withdrawal–induced apoptosis in HASMCs. Importantly, inhibition of SK1 by either a competitive inhibitor N′,N′-dimethylsphingosine or expression of dominant-negative mutant of SK1(G82D) or specific small interference RNA knockdown substantially attenuated hyperglycemia-induced anti-apoptotic effect and anti-apoptotic protein Bcl-2 expression in HASMCs. Moreover, SK1-mediated anti-apoptotic effect requires the intracellular effects of sphingosine-1-phosphate. We conclude that hyperglycemia stimulates SK1 activity via PKC- and oxidative stress–dependent pathways, leading to decreased apoptosis in HASMCs. Taken together, these observations have important implications for understanding the roles of the SK1 signaling pathway in the pathogenesis of diabetic vasculopathy.
Toxic Human Islet Amyloid Polypeptide (h-IAPP) Oligomers Are Intracellular, and Vaccination to Induce Anti-Toxic Oligomer Antibodies Does Not Prevent h-IAPP–Induced β-Cell Apoptosis in h-IAPP Transgenic Mice
Authors: Lin Chia-Yu , Gurlo Tatyana , Kayed Rakez , Butler Alexandra E. , Haataja Leena , Glabe Charles G. , Butler Peter C.
Published: April 2007

OBJECTIVE—Islets in type 2 diabetes are characterized by a deficit in β-cells, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). The toxic form of amyloidogenic protein oligomers are distinct and smaller than amyloid fibrils and act by disrupting membranes. Using antibodies that bind to toxic IAPP oligomers (but not IAPP monomers or fibrils) and a vaccination-based approach, we sought to establish whether IAPP toxic oligomers form intra- or extracellularly and whether vaccination to induce anti-toxic oligomer antibodies prevents IAPP-induced apoptosis in human IAPP (h-IAPP) transgenic mice.

RESEARCH DESIGN AND METHODS—Pancreas was sampled from two h-IAPP transgenic mouse models and examined by immunohistochemistry for toxic oligomers. The same murine models were vaccinated with toxic oligomers of Alzheimer β protein (AβP1–40) and anti-oligomer titers, and blood glucose and islet pathology were monitored.

RESULTS—Toxic oligomers were detected intracellularly in ∼20–40% of h-IAPP transgenic β-cells. Vaccine induced high titers of anti–h-IAPP toxic oligomers in both transgenic models, but β-cell apoptosis was, if anything, further increased in vaccinated mice, so that neither loss of β-cell mass nor diabetes onset was delayed.

CONCLUSIONS—IAPP toxic oligomers form in h-IAPP transgenic mouse models, and anti-toxic oligomer antibodies do not prevent h-IAPP–induced β-cell apoptosis. These data suggest that prevention of h-IAPP oligomer formation may be more useful than a vaccination-based approach in the prevention of type 2 diabetes.
Pharmacological Inhibition of Glucosylceramide Synthase Enhances Insulin Sensitivity
Authors: Aerts Johannes M. , Ottenhoff Roelof , Powlson Andrew S. , Grefhorst Aldo , van Eijk Marco , Dubbelhuis Peter F. , Aten Jan , Kuipers Folkert , Serlie Mireille J. , Wennekes Tom , Sethi Jaswinder K. , O'Rahilly Stephen , Overkleeft Hermen S.
Published: April 2007

A growing body of evidence implicates ceramide and/or its glycosphingolipid metabolites in the pathogenesis of insulin resistance. We have developed a highly specific small molecule inhibitor of glucosylceramide synthase, an enzyme that catalyzes a necessary step in the conversion of ceramide to glycosphingolipids. In cultured 3T3-L1 adipocytes, the iminosugar derivative N-(5′-adamantane-1′-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM) counteracted tumor necrosis factor-α–induced abnormalities in glycosphingolipid concentrations and concomitantly reversed abnormalities in insulin signal transduction. When administered to mice and rats, AMP-DNM significantly reduced glycosphingolipid but not ceramide concentrations in various tissues. Treatment of ob/ob mice with AMP-DNM normalized their elevated tissue glucosylceramide levels, markedly lowered circulating glucose levels, improved oral glucose tolerance, reduced A1C, and improved insulin sensitivity in muscle and liver. Similarly beneficial metabolic effects were seen in high fat–fed mice and ZDF rats. These findings provide further evidence that glycosphingolipid metabolites of ceramide may be involved in mediating the link between obesity and insulin resistance and that interference with glycosphingolipid biosynthesis might present a novel approach to the therapy of states of impaired insulin action such as type 2 diabetes.
Effects of Dipeptidyl Peptidase-4 Inhibition on Gastrointestinal Function, Meal Appearance, and Glucose Metabolism in Type 2 Diabetes
Authors: Vella Adrian , Bock Gerlies , Giesler Paula D. , Burton Duane B. , Serra Denise B. , Saylan Monica Ligueros , Dunning Beth E. , Foley James E. , Rizza Robert A. , Camilleri Michael
Published: April 2007

OBJECTIVE— We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations.

RESEARCH DESIGN AND METHODS— We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design.

RESULTS— Fasting (7.3 ± 0.5 vs. 7.9 ± 0.5 mmol/l) and peak postprandial (14.1 ± 0.6 vs. 15.9 ± 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 ± 1.6 vs. 23.7 ± 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 ± 270 vs. 1,277 ± 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments.

CONCLUSIONS— Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.
New Orleans, Invisible City
Authors: Daly Erin Moore
Published: April 2007

This article explores the hidden, suppressed elements of New Orleans leading up to and immediately following Hurricane Katrina. The article is juxtaposed with excerpts from Italo Calvino's Invisible Cities in order to provide a lens through which to ask questions not typically raised by government officials, city planners, and science and technology experts. This uncovers aspects of New Orleans that must not be overlooked in the rebuilding process. If policy, culture, and technology render aspects of New Orleans invisible, then only by revealing these aspects can one ascertain the truth of the city.
Ages of Reorganization: Self-organization in the World System
Authors: Modelski George
Published: April 2007

Dark ages is a familiar, if untheorized, term of world history. We propose to generalize that concept, and to reinterpret it as "ages of reorganization." We do this by viewing the two major periods of past dark ages as phases of world community formation—this being one of a cascade of processes that make up world system evolution. This reconceptualization allows us to see contemporary developments as the onset of another millennial age of readjustment, understood also as a world system mechanism of self-organization. It is a means whereby the threatening features of earlier developments—those of the preceding ages of concentration—are reined in automatically, as it were, to contain the dangers that they might harbor. We propose to take up these themes, recently opened up by Sing Chew in two recent papers (2002a, 2000b), and will review the following questions in response (in the light of the recently consolidated "World Cities" database): (1) How robust is the concept of dark ages? (2) Have dark ages been features of world system history? (3) Are there grounds to assume the workings of an evolutionary process? (4) Have we already entered upon the modern age of reorganization?
Antibody‐Functionalized Hybrid Superparamagnetic Nanoparticles
Authors: Arruebo M. , Fernández‐Pacheco R. , Velasco B. , Marquina C. , Arbiol J. , Irusta S. , Ibarra M. R. , Santamaría J.
Published: April 2007

Superparamagnetic hybrid nanoparticles (ca. 80 nm) are obtained. They consist of an inner iron oxide core coated by a silica shell, which is in turn functionalized with amine or carboxyl groups and covalently coupled to a monoclonal antibody (anti‐hCG; hCG = human chorionic gonadotropin). The prepared nanoparticles show a specific magnetic moment (per gram of iron) that is comparable to that measured for commercial superparamagnetic iron oxide preparations. The bioactivity of the antibody‐conjugated magnetic nanoparticles is verified by a standard bioassay. These results indicate the potential of the hybrid nanoparticles prepared for use as enhanced contrast agents in magnetic resonance imaging applications.
Aligned Porous Structures by Directional Freezing
Authors: Zhang H. , Cooper A. I.
Published: April 2007

Materials with aligned porous structures have broad potential in applications such as organic electronics, microfluidics, and tissue engineering. Materials of this type can be fabricated using techniques such as microfabrication, soft lithography, and photolithography. Directional freezing is a cheap, simple, and novel route to prepare aligned porous materials in the form of 2D surface patterns or 3D monolithic structures. A solvent—typically water but also organic solvents or carbon dioxide—is frozen unidirectionally and the pore structure is templated from the aligned solvent crystals that are formed. These methods can produce complex composite materials with a range of aligned pore architectures.
Diagnostic challenges in a severely delayed infant with hypersomnolence, failure to thrive and arteriopathy: A unique case of γ‐hydroxybutyric aciduria and Williams syndrome
Authors: Knerr Ina , Michael Gibson K. , Ganesh Jaya , Bennett Michael J. , Salomons Gajja S. , Jakobs Cornelis , Myers Scott M.
Published: April 2007

Metabolic work‐up, pursued in a 5‐month‐old female infant with hypersomnolence, failure to thrive, and global developmental delay, led to the identification of γ‐hydroxybutyric aciduria (GHB). Succinic semialdehyde dehydrogenase deficiency (SSADH deficiency) was confirmed enzymatically and molecularly. Characteristic dysmorphic facies, cardiovascular anomalies, and hypercalcemia led to clinical suspicion of Williams‐Beuren syndrome (WS), confirmed by cytogenetic studies. This rare occurrence of two unrelated genetic conditions highlights the importance of instituting comprehensive metabolic studies despite the presence of syndromic findings, even in the absence of other metabolic abnormalities that may be indicative of metabolic disease such as hyperammonemia, hypoglycemia, ketonuria, and metabolic acidosis. © 2007 Wiley‐Liss, Inc.
Von Glycerin zu höherwertigen Produkten
Authors: Pagliaro Mario , Ciriminna Rosaria , Kimura Hiroshi , Rossi Michele , Della Pina Cristina
Published: April 2007

Wegen des großen Überschusses an Glycerin, das als Beiprodukt der Herstellung von Biodiesel anfällt, werden gegenwärtig Industrieanlagen zur Glycerinproduktion geschlossen, während andere, die Glycerin als Rohstoff verwenden, in Betrieb genommen werden. Forschungsvorhaben mit dem Ziel, neue Anwendungen für Glycerin als günstiges Ausgangsmaterial für funktionelle Derivate zu erschließen, führten zu einer Reihe selektiver Verfahren zur Umwandlung von Glycerin in höherwertige Produkte. Dieser Kurzaufsatz beschreibt ausgewählte Ergebnisse und zeigt, dass Glycerin zu einem zentralen Rohstoff in zukünftigen chemischen Industriezweigen aufsteigt.
From Glycerol to Value‐Added Products
Authors: Pagliaro Mario , Ciriminna Rosaria , Kimura Hiroshi , Rossi Michele , Della Pina Cristina
Published: April 2007

Today, industrial plants that produce glycerol are closing down and others are opening that use glycerol as a raw material, owing to the large surplus of glycerol formed as a by‐product during the production of biodiesel. Research efforts to find new applications of glycerol as a low‐cost feedstock for functional derivatives have led to the introduction of a number of selective processes for converting glycerol into commercially valued products. This Minireview describes a selection of such achievements and shows how glycerol will be a central raw material in future chemical industries.
Dielectric characterization of bacterial cells using dielectrophoresis
Authors: Sanchis A. , Brown A. P. , Sancho M. , Martínez G. , Sebastián J. L. , Muñoz S. , Miranda J. M.
Published: April 2007

Measurements of dielectrophoretic collection spectra of Escherichia coli and Staphylococcus aureus suspensions are used for obtaining dielectric characteristics of both types of bacteria. The experiments are interpreted using a numerical method that models the cells as compartmented spherical or rod‐like particles. We show the usefulness of this simple method to extract significant information about the electrical properties of Gram‐negative and ‐positive bacteria. Bioelectromagnetics 28:393–401, 2007. © 2007 Wiley‐Liss, Inc.
Inferences Concerning a Mean Vector when the Variables are Grouped into Subsets
Authors: Subbaiah Perla , Mudholkar Govind S.
Published: April 2007

In experiments involving multivariate measurements biological considerations often indicate a grouping of the variables into subsets such that all the variables in a subset are equally important and the subsets may be arranged in a decreasing order of importance (JENSEN, 1972). This paper deals with a method of analysis appropriate in such cases, to solve multivariate problems such as profile analysis, comparison of two mean vectors, or univariate problems such as analysis of SCHEFFÉ'S mixed effects model with interaction (SCHEFFÉ, 1959; MILLER, 1966), usually treated using HOTELLING'S T2. An invariance structure underlying this procedure is examined and used to obtain noncentrality parameters of the power function, and derive some of its properties. The multiple comparisons procedure in MUDHOLKAR and SUBBAIAH (1976) is extended and illustrated in terms of the data from a clinical trial.
A Modified Chi‐squared Approach for Fitting WEIBULL Models to Synthetic Life Tables1
Authors: Freeman Daniel H. , Freeman Jean L. , Koch Gary G.
Published: April 2007

WEIBULL models are fitted to synthetic life table data by applying weighted least squares analysis to log log functions which are constructed from appropriate underlying contingency tables. As such, the resulting estimates and test statistics are based on the linearized minimum modified X21‐criterion and thus have satisfactory properties in moderately large samples. The basic methodology is illustrated in terms of an example which is bivariate in the sense of involving two simultaneous, but non‐competing, vital events. For this situation, the estimation of WEIBULL model parameters is described for both marginal as well as certain conditional distributions either individually or jointly.
The Length of a Generation
Authors: Lefkovitch L. P.
Published: April 2007

After comparing a number of definitions of the length of a generation, two new ones are proposed. One is the mean age of mothers having new born children in the current population, the other is the period of decay of departures from the stable age distribution. Numerical examples are given.
First Results of Definition and Reduction of Characteristics and Discrimination in Multivariable Psychophysiological Investigations
Authors: Hiller E. , Wernecke K.‐D. , Michel J. , Chatiaschwili W. G.
Published: April 2007

In this paper, the statistical analysis of the comprehensive data obtained from multivariable dynamic (psychophysiological) tests by means of a hybrid computing system and the results obtained are represented. Focal point is the establishment of a set of characteristics according to pertinent and statistical aspects as well as the application of the multivariate variance and discrimination analysis to this set of characteristics for the classification of given “reaction types” (RT). The discriminations carried out for the classes made visible the differences between them clearly. The physiological and possible pathophysiological significance of the results cannot be dealt with in this paper.