bluuebunny/crossref_metadata_2025 huggingface dataset:
The retention of newly‐acquired brushing and flossing skills
Authors: Stewart James E. , Wolfe Gary R.
Published: December 2005

Abstract Brushing and flossing ability increased dramatically 3 weeks following 2 sessions of oral hygiene instructions. At the same time, the plaque index for these patients decreased significantly. 1 year after the oral hygiene instruction, the plaque index for these patients returned to the pre‐intervention levels. However, these patients were able to maintain their 3‐week post‐intervention brushing and flossing scores. We conclude that increased levels of plaque 1 year later, was not due to loss of brushing and flossing skills.
Adhesion of stainable, calcium–rich deposits on substrata with different surface free energies
Authors: Uyen H. M. , van Dijk L. J. , Busscher H. J.
Published: December 2005

Abstract Calculus plays an important role in chronic inflammatory periodontal disease and tooth loss. Patients can suffer from calculus formation despite good oral hygiene. The strength of adhesion between calculus and the enamel surface, though not determinant for the formation of calculus itself, determines whether calculus remains on the teeth during eating and toothbrushing. In this study, the amount and the strength of adhesion of calcium‐rich deposits formed in vivo on different materials are related to substrate surface free energies (sfe). In 4 beagle dogs, fenestrated crowns were made on the upper fourth premolars. Smooth facings of glass (sfe 120 mJ·m‐2), polished bovine enamel (sfe 85 mJ·m‐2), polymethylmethacrylate (PMMA sfe 56 mJ·m‐2) and polytetafluorethylene (PTFE sfe 20 mJ·m‐2) were inserted in the crowns for 1, 3, 7, 14 or 28 days. The amount of deposit was evaluated both gravimetrically and planimetrically using Alizarin Red S for staining. Adhesion of calcium‐rich deposits was evaluated planimetrically by studying their removal in a brushing machine. Dry weight increased linearly with time (approximately 0.18 mg·cm‐2 per day) and was slightly less on PTFE than on the other materials. After 1 to 3 days, staining already revealed a 100% coverage by calcium‐rich deposits. The number of strokes required to reduce the planimetric scores by 63% was extremely small on PTFE and PMMA and related with substrate surface free energies. This study shows that a possible way to reduce calculus formation in vivo is to decrease the surface free energy of the enamel using appropriate surfactants in, e.g., toothpastes.
A 10–year retrospective study of periodontal disease progression
Authors: Papapanou Panos N. , Wennström Jan L. , Gröndahl Kerstin
Published: December 2005

Abstract The purpose of this study was to record the rate of periodontal disease progression over a 10‐year period with respect to individual subject, age and tooth type. 283 subjects, who had undergone a full‐mouth radiographic examination in 1974–76 and at that time were 25–70 years old, were randomly selected from a larger patient sample for a new radiographic examination in 1985–86. 201 subjects (71%) agreed to participate. For each respondent, tooth loss over the 10‐year period was calculated‐The radiographic bone height at the mesial and distal aspect of all teeth was assessed by measuring the distance between the cemento‐enamel junction and the bone crest. Difference in periodontal bone height between the 2 examinations was calculated for each tooth site. The results revealed that the mean number of teeth lost over the 10‐year period was 3.8 (SD 4.6). Tooth mortality, expressed as a % of the no. of teeth present at the initial examination, increased with age and varied between 2.9%‐28.5%. In all age groups, molars had the highest and canines the lowest rate of tooth mortality. The frequency of subjects with loss of > 10 teeth was highest for the initially 45‐year old individuals (20%). 7 individuals (3%) had become edentulous. The mean annual reduction of alveolar bone height varied between 0.07–0.14 mm in the age groups 25–65 years. The initially 70‐year old subjects showed a statistically significant higher annual rate of bone loss (0.28 mm). A mean bone loss over the 10–year period of ≥0.5 mm was observed in ∼75% of all the subjects, while 7% showed a mean bone loss of ≥3 mm. About 55% of the tooth sites had lost between 0.5–2.0 mm in periodontal bone height and 16% showed a longitudinal bone loss of >2 mm. 10 sites or more with longitudinal bone loss of 6 mm were found in 4% of the subjects and ∼ 15% of the subjects accounted for half of the totally recorded tooth sites with a 6 mm longitudinal bone loss.
Systemic metronidazole in the treatment of periodontitis
Authors: Jenkins W. M. M. , MacFarlane T. W. , Gilmour W. H. , Ramsay I. , MacKenzie D.
Published: December 2005

Abstract The present study evaluated the effect of systemic metronidazole on advanced periodontitis in 10 patients with inadequate oral hygiene. Clinical and microbiological observations were made at a total of 173 bleeding pockets of 5 mm depth or more. The clinical observations comprised plaque index scores, dichotomous measurements of gingival redness and suppuration, pocket depths and attachment levels. The microbiological variables investigated were the % spirochaetes, % black‐pigmented Bacteroides species. % facultative streptococci and presence or absence of Bacteroides gingivalis. At baseline, after clinical measurements and microbiological samples had been taken, each patient received a thorough scaling and root planing. After 3 months, the clinical measurements and microbiological sampling were repeated and a 5‐day course of metronidazole was administered while one side of the mouth was scaled and root planed. After a further 3 months, the final measurements and samples were taken. In comparing pre‐and post‐treatment data, the following significant differences were observed: for debridement alone, a reduction in mean % spirochaetes from 11.5% to 4.9% and an increase in mean % streptococci from 4.7% to 8.8%; for metronidazole alone, a 0.3 mm gain in mean attachment level, a 0.4 mm reduction in mean pocket depth and a reduction in the frequency of suppurating sites from 32% to 16%; for debridement plus metronidazole. a 0.2 mm gain in mean attachment level, a 0.5 mm reduction in mean pocket depth and a reduction in mean % spirochaetes from 5.6% to 2.5%. Thus systemic metronidazole, either alone or accompanied by debridement, produced a modest clinical improvement after debridement alone had failed. However, if the P‐values are adjusted to account for the fact that multiple significance tests have been carried out, only the reduction in % spirochaetes following debridement alone would remain significant. It was concluded that systemic metronidazole could not be justified in the periodontal management of this group of patients.
Gingival health and gingivitis development during puberty
Authors: Mombelli A. , Gusberti F. A. , van Oosten M. A. C. , Lang N. P.
Published: December 2005

Abstract The purpose of this investigation was to follow the development of the gingival conditions during puberty and to correlate oral clinical parameters with chronological age as well as with parameters used for the determination of the pubertal development. In 22 boys and 20 girls pubertal and skeletal development, as well as plaque index (PII) and gingival index (GI) were monitored at 1‐year intervals between the ages of 11 and 15 years. During this time, the papillary bleeding index (FBI) was assessed 10 times in all interdental spaces of the dentition. The bleeding tendency, represented by whole mouth mean FBI values, as well as the % of bleeding interdental sites, was found to increase significantly with the start of the pubertal phase. It reached a peak value after 1–5 years in 35% of the children. A significant trend of decrease was noted after the age of 14 years in boys and girls. In boys, mean FBI and the % of interdental sites with bleeding were correlated with testes growth, in girls with the Tanner index for secondary sex characteristics (breast development). PII and GI. which were only recorded annually, did not show a significant trend of increase or decrease.
Gingivitis in the deciduous and permanent dentition
Authors: Berglundh T. , Liljenberg B. , Ericsson I. , Lindhe J.
Published: December 2005

Abstract The present investigation was performed in order to study the reaction of the gingiva in the deciduous and permanent dentition of dogs to 3 weeks of plaque accumulation. The study was carried out in 10 beagles, divided into 2 groups of 5 dogs each; group I and group II. When the dogs of group I were (0 weeks old, a meticulous plaque control regimen was initiated in order to establish clinically healthy gingiva. After 6 weeks of plaque control, the gingivae of the lower deciduous molars was exposed to a clinical examination, and biopsies as well as bacterial plaque samples were harvested from tooth 03P and 02P. A second plaque control regimen was initiated when the same dogs were 15 months old. After 6 weeks of plaque control, the gingiva of the permanent dentition was examined and biopsies sampled from tooth P3 and P4. In the dogs of group II, plaque control regimens of 3 weeks duration were initiated when the animals were 10 weeks and 15 months old. Clinical examinations were performed at the end of each 3‐week period. Immediately after the clinical examinations, 3‐week periods of plaque accumulation were initiated. Examinations and plaque sampling were performed after each of these 3‐week periods and biopsies were sampled from the deciduous and permanent dentition as described for group I. The biopsies were processed for Histometric and morphometric measurements. The findings from the experiment showed that careful plaque control resulted in the establishment of clinically healthy gingiva. In both the deciduous and permanent dentition, however, a clinically healthy gingiva was found to contain a small inflammatory cell infiltrate (ICT). 3 weeks of plaque accumulation resulted in both dentitions in the development of clinical signs of gingivitis and in the formation of comparatively large ICT. The large ICT of the permanent gingiva resided in the coronal portion of the free gingival unit, while in the deciduous dentition, the inflammatory lesion occupied a narrow tissue portion along the entire border of the dento‐gingival epithelium. The ICT of the permanent gingiva harbored a larger portion of plasma cells than the inflammatory lesion studied in the deciduous dentition.
The effect of a systemically‐administered nonsteroidal anti‐inflammatory drug (flurbiprofen) on experimental gingivitis in humans*
Authors: Heasman P. A. , Seymour R. A.
Published: December 2005

Abstract. Non‐steroidal anti‐inflammatory drugs reduce the acute inflammatory reaction and alveolar bone loss of experimental periodontitis in dogs by mechanisms thought to be associated with the inhibition of prostaglandin synthesis. 25 healthy volunteers abstained from tooth cleaning for 21 days. Experimental gingivitis developed in all subjects. On day 21, the subjects were divided into 3 treatment groups; oral flurbiprofen (100 mg/day) + toothbrushing (A), placebo + toothbrushing (B) and oral flurbiprofen (100 mg/day) only (C). Treatment continued for 6 days. Plaque indices (PI), gingival indices (GI) and probing pocket depths (PPD) were recorded at 6 points on each of 6 maxillary teeth on days 1, 22, 23, 24 and 27. Crevicular fluid flow (CFF) was quantified with a Periotron on days 1. 22 and 27 in groups A and B, and on days 1 and 27 in group C. There were no changes in PPD throughout the study. A reduction of GI occurred between days 22 and 27 for all treatment groups. CFF was also reduced between days 22 and 27 in groups A and B. The differences between the 3 treatments were very small. It is concluded that systemic flurbiprofen (100 mg/day) can reduce the signs of an experimental gingivitis over 6 days. This effect may be seen when the drug is used alone and as an adjunct to toothbrushing.
Effects on gingivitis of daily rinsing with 1.5% H202
Authors: Boyd R. L.
Published: December 2005

Abstract. The purpose of this study was to compare 2 groups of adolescents undergoing orthodontic treatment with fixed appliances to determine whether once daily use of a mouthrinse containing 1.5% H2O2: along with toothbrushing would be better than toothbrushing alone in maintaining their periodontal health. The 2 groups of subjects were selected non‐randomly but were matched for age and sex. The control group (N=34) used toothbrushing and a mint‐flavored 0.05% NaF mouthrinse once daily, while the treatment group (N=25)used tooth‐brushing and a once daily rinse with a preparation containing 0.05% NaF and 1.5% H2O2 (Orthoflur®). 2 calibrated clinical examiners made single‐blind clinical assessments of the plaque index, gingival index, and bleeding tendency in 6 standard sites per subject. They also noted any generalized mucosal irritations or staining of the teeth or tongue. Assessments were made before appliances were placed (baseline) and 1, 3, 6, 9, 12 and 18 months after appliances were placed. Results indicated that although there were no significant differences at baseline, the Orthoflur group had significantly fewer study sites with gingival index or bleeding tendency scores greater than 1 than the control group from the 1‐month through the 18‐month examinations (P<0.01), and significantly fewer sites with plaque index greater than 1 and bleeding tendency scores of 2 or more from the 3‐month through the 18‐month examinations (P<0.02 and 0.01. respectively). No generalized mucosal irritations or clinically significant staining of the tongue or teeth were noted in either group during the study.
Relationship of clinical parameters to attachment loss in subsets of subjects with destructive periodontal diseases
Authors: Halazonetis T. D. , Haffajee A. D. , Socransky S. S.
Published: December 2005

Abstract. 23 subjects were followed prior to treatment for 5 to 12 months in an attempt to relate attachment loss during this period to attachment level, probing depth, gingival redness and bleeding on probing. The subjects were divided into 3 groups based on amount and distribution of prior attachment loss: minor periodontitis, predominantly molar periodontitis and generalized periodontitis. The % of sites that exhibited attachment loss during the study period in the minor periodontitis, predominantly molar periodontitis and generalized periodontitis groups, were 1.3, 8.1 and 5.4, respectively. Subjects with minor periodontitis and predominantly molar periodontitis exhibited attachment loss more frequently in molar sites, proximal sites and sites with attachment level 4 mm. In subjects with generalized periodontitis, attachment loss was related to tooth surface and attachment level, but not to tooth type. The relationship between the clinical parameters and attachment loss was improved compared with previous studies by using more homogeneous subject groups, more sensitive methods of analyzing attachment change and multivariate data analysis. However, the clinical parameters could not be used as diagnostic tests to predict attachment loss at individual sites.
Validity and reliability of alveolar bone level measurements made on dry skulls
Authors: Albandar Jasim M.
Published: December 2005

Abstract. The validity of the radiographic alveolar bone level measurements in relation to direct measurements, and the reliability of both the direct and the radiographic measurements were estimated on dry skulls. The CEJ‐AC distances in the proximal areas of teeth in 6 dry skulls were assessed directly, on periapical radiographic films taken with the Eggen film holder only and on films taken with the film holder and a rubber impression material. The validity of the bone level measurements made on films taken by the 2 radiographic techniques was evaluated by comparing each of these 2 with the direct measurements by means of the paired t‐test. The reliability of the measurements made by each of the 3 methods was estimated by means of the test‐retest. the paired t‐test and the direct error estimation methods. It was found that both radiographic methods significantly underestimated the proximal bone level (p<0.001). There were no significant differences between the test‐retest scoring of the bone level in any of the 3 methods. However, the measurements made by both radiographic techniques showed better correlations, and smaller error due to the measurement technique than the direct measurements. When repeated radiographic exposures were made, the exposure technique in method C produced no error, while the estimated error variance in method B was 0.07. It was concluded that the validity and the reliability of both radiographic methods were satisfactory and that the observed underestimation has little impact on longitudinal studies monitoring the alveolar bone level changes.
Periodontal treatment needs in populations of high‐ and low‐fluoride areas of Morocco
Authors: Haikel Youssef , Turlot Jean‐Christoph , Cahen Pierre‐Michel , Frank Robert
Published: December 2005

Abstract. The purpose of this study was to determine the periodontal status and treatment needs, using the CPITN index, in a population aged 7 to 60 years residing in the fluorosis area of Khouribga and the non‐fluorosis area of Beni‐Mellal, Morocco. A total of 2378 subjects was studied. In the youngest age groups, more subjects and sextants from Khouribga than from Beni‐Mellal were free of periodontal diseases. Conversely, in Beni‐Mellal, subjects in the youngest age groups presented a higher mean number of sextants with calculus than those from Khouribga. In combining the 2 areas, 1.3% of the 2319 dentate subjects examined needed no treatment and 98.7% needed at least oral hygiene instructions (TNI). The present study, based on the CPITN index, demonstrated in both areas a high prevalence of gingivitis, and a relatively low prevalence of deep pocketing, occurring on the average in less than half a sextant in the total populations.
Direct measurement of the bactericidal effect of chlorhexidine on human dental plaque
Authors: Netuschil L. , Reich E. , Brecx M.
Published: December 2005

Abstract The purpose of the present study was to determine by means of a fluorescence test the ratio between vital and dead bacteria in dental plaque before and after 0.1 % chlorhexidine rinses. Plaque was stained by fluoresceindiacetate (FDA), which gave a green color to the living micro‐organisms, and by ethidiumbromide (EB), which introduced a red color into the nucleic acids of the dead bacteria. 1‐, 2‐ and 3‐day‐old undisturbed plaque harbored 80 to 85% living micro‐organisms. 1 h after chlorhexidine use, this % was reduced to a plateau of 19 to 34% of vital bacteria present in the sampled plaque. Between 6 and 8 h later, this % rose towards its original value. This study has shown that FDA/EB staining provides a method for direct measurement of bacteria vitality in dental plaque and, as such, can be of great value for testing the efficacy of various antiplaque agents.
Diagnostic problems of periodontitis‐like lesions caused by eosinophilic granuloma
Authors: Nicopoulou‐Karayianni K. , Mombelle A. , Lang N. P.
Published: December 2005

Abstract Eosinophilic granuloma is the localized and mildest form of histiocytosis X. It is a destructive osseous lesion characterized by large numbers of eosinophils and histiocytes. The etiology of the disease is unknown. Frequently the jaws, including the periodontium, are involved and the disease simulates severe localized periodontitis. A case of eosinophilic granuloma of the jawbone is presented. The pertinent clinical features are emphasized and possible problems in the interpretation of clinical periodontal features are discussed.
The effectiveness of root debridement in open flap procedures by means of a comparison between hand instruments and diamond burs
Authors: Schwarz Jean‐Pierre , Guggenheim Richard , Düggelin Marcel , Hefti Arthur F. , Rateitschak‐Plüss Edith M. , Rateitschak Klaus H.
Published: December 2005

Abstract The goal of the present in vivo study was to evaluate human roots by means of scanning electron microscopy (SEM), after treating the root surfaces either with conventional hand instruments or with newly developed diamond burs. Peculiar root anatomy often makes perfect instrumentation with hand instruments difficult or impossible. On 20 teeth destined for extraction because of severe periodontitis, the root surfaces were exposed by mucoperiosteal flap procedures. Ten roots were then planed using fine curettes, and 10 were instrumented using diamond burs. Following extraction, the root surfaces were stained and photographed. Stained areas were examined by SEM. On the 20 test teeth, 79 surfaces were evaluated. From these, 381 stained zones were checked by SEM for the presence of bacteria. A total of 216 stained areas from teeth treated by hand instruments was evaluated; 15 of these (6.9%) contained bacteria. Of roots treated by diamond burs, 165 stained areas were evaluated; 9 (5.5%) exhibited bacteria. Thus, both methods resulted in root surfaces that were essentially bacteria‐free.
Serum IgG antibodies reactive with lipoteichoic acid in adult patients with periodontitis
Authors: Monefeldt Kari , Tollefsen Tore
Published: December 2005

Abstract IgG antibody levels to lipoteichoic acid (LTA), prepared from Streptococcus mutans cells, were determined by enzyme‐linked immunosorbent assay in serum samples from 149 subjects. An extract from Bacteroides gingivalis and lipopolysaccharide from Escherichia coli 055:B5 served as control antigens. The reference group comprised 28 systemically and periodontally healthy adults. The main lest groups were: 52 persons with gingivitis only, and 69 patients with periodontitis. Within those groups, 37 patients had insulin‐dependent diabetes mellitus, another 20 patients were prospective or renal transplant recipients. The periodontitis patient group showed significantly (p < 0.05) higher mean antibody value and higher frequency of extreme antibody responses to both LTA and B. gingivalis than the gingivitis group. LPS did not discriminate between the groups. Multiple regression analysis with gingivitis scores as the dependent variable selected plaque scores, anti‐LTA antibody values and general health status as significant (p < 0.05) regressors. The variance in radiographical alveolar bone loss was significantly (p < 0.05) explained by age and by antibody values to B. gingivalis and to LTA. The patients with extreme immunological responsiveness to LTA or to B. gingivalis had about twice as much alveolar bone loss as those with normal serological reactivity. The results support the contention that LTA modulates the progression of periodontitis in humans.
BIANCHI IX GROUP-MANIFOLD REDUCTIONS OF GRAVITY
Authors: LINARES ROMAN
Published: December 2005

We exhibit a new way to perform the group-manifold reduction of pure Einstein gravity in the vielbein formulation when the compactification group manifold is S3. The new Bianchi IX group-manifold reduction is obtained by exploiting the two three-dimensional Lie algebras that the S3 group manifold admits. As an application of the new reduction we show that there exists a domain wall solution to the lower-dimensional theory which upon uplifting to the higher-dimension turns out to be the self-dual (in the nonvanishing components of both curvature and spin connection) Kaluza–Klein monopole.
A GENERATION MODEL OF COMPOSITE LEPTONS AND QUARKS
Authors: ROBSON B. A.
Published: December 2005

A new composite model for leptons and quarks is presented. The model treats leptons and quarks as composites of three kinds of spin-½ particles (rishons), which belong to a fundamental triplet representation of a flavor SU (3) symmetry. A super-strong color-type force binds rishons together to form colorless leptons or quarks. Quarks display a valence property, which corresponds to the quark color of the Standard Model. Leptons have no valence property and are inert with respect to the super-strong color interaction. Both the strong color force and the weak interaction of the Standard Model are residual interactions of the super-strong color force in the new model.
NEUTRON SPIN POLARIZATION IN STRONG MAGNETIC FIELDS
Authors: WEN H. , KISSLINGER L. S. , GREINER WALTER , MAO G.
Published: December 2005

The effects of strong magnetic fields on the inner crust of neutron stars are investigated after taking into account the anomalous magnetic moments of nucleons. The energy spectra and wave functions for protons and neutrons in a uniform magnetic field are provided. The particle spin polarizations and the yields of protons and neutrons are calculated in a free Fermi gas model. Obvious spin polarizations occur when B≥1014 G for protons and B≥1017 G for neutrons, respectively. It is shown that the neutron spin polarization depends solely on the magnetic field strength.
INFORMATION ENTROPY AND NUCLEON CORRELATIONS IN NUCLEI
Authors: MASSEN S. E. , PSONIS V. P. , ANTONOV A. N.
Published: December 2005

We evaluated the information entropies in coordinate and momentum spaces and their sum (Sr, Sk, S) for many nuclei using "experimental" densities or/and momentum distributions. The results are compared with the harmonic oscillator model and with the short-range correlated distributions. Suppose A is the number of nuclei, it is found that Sr depends strongly on ln A and does not depend very much on the model. The behavior of Sk is the opposite. The various cases that we consider can be classified according to either the quantity of the experimental data that we use or by the values of S, i.e., the increase in the quality of the density and in the momentum distributions leads to an increase in the values of S. In all cases, apart from the linear relation S=a+b ln A, the linear relation S=aV+bV ln V also holds. V is the mean volume of the nucleus. If S is considered as an ensemble entropy, a relation between A or V and the ensemble volume can be found. Finally, comparing many different electron scattering experiments for the same nucleus, we found that the larger the momentum transfer ranges, the larger the information entropy is. It is concluded that S might be used to compare different experiments for the same nucleus, and to choose the most reliable one.
GROUND STATE AND β-VIBRATIONAL BANDS OF AXIAL-SYMMETRIC SUPERHEAVY NUCLEI
Authors: SHARIPOV SH. , ERMAMATOV M. J.
Published: December 2005

The spectra, E2-transition probabilities and electric quadrupole moments of a series of known superheavy nuclei, with Z between 102 and 112 are analyzed within the non-adiabatic model of quadrupole deformed, axially-symmetric nuclei. Calculations are made assuming that the mass parameter and the non-dimensional parameter g appearing in this model are constant for the superheavy nuclei with close charge numbers.
Inosine released after hypoxia activates hepatic glucose liberation through A3adenosine receptors
Authors: Guinzberg Raquel , Cortés Daniel , Díaz-Cruz Antonio , Riveros-Rosas Héctor , Villalobos-Molina Rafael , Piña Enrique
Published: December 2005

Inosine, an endogenous nucleoside, has recently been shown to exert potent effects on the immune, neural, and cardiovascular systems. This work addresses modulation of intermediary metabolism by inosine through adenosine receptors (ARs) in isolated rat hepatocytes. We conducted an in silico search in the GenBank and complete genomic sequence databases for additional adenosine/inosine receptors and for a feasible physiological role of inosine in homeostasis. Inosine stimulated glycogenolysis (≈40%, EC504.2 × 10−9M), gluconeogenesis (≈40%, EC507.8 × 10−9M), and ureagenesis (≈130%, EC507.0 × 10−8M) compared with basal values; these effects were blunted by the selective A3AR antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino][1,2,4]-triazolo[1,5- c]quinazoline (MRS 1220) but not by selective A1, A2A, and A2BAR antagonists. In addition, MRS 1220 antagonized inosine-induced transient increase (40%) in cytosolic Ca2+and enhanced (90%) glycogen phosphorylase activity. Inosine-induced Ca2+mobilization was desensitized by adenosine; in a reciprocal manner, inosine desensitized adenosine action. Inosine decreased the cAMP pool in hepatocytes when A1, A2A, and A2BAR were blocked by a mixture of selective antagonists. Inosine-promoted metabolic changes were unrelated to cAMP decrease but were Ca2+dependent because they were absent in hepatocytes incubated in EGTA- or BAPTA-AM-supplemented Ca2+-free medium. After in silico analysis, no additional cognate adenosine/inosine receptors were found in human, mouse, and rat. In both perfused rat liver and isolated hepatocytes, hypoxia/reoxygenation produced an increase in inosine, adenosine, and glucose release; these actions were quantitatively greater in perfused rat liver than in isolated cells. Moreover, all of these effects were impaired by the antagonist MRS 1220. On the basis of results obtained, known higher extracellular inosine levels under ischemic conditions, and inosine’s higher sensitivity for stimulating hepatic gluconeogenesis, it is suggested that, after tissular ischemia, inosine contributes to the maintainence of homeostasis by releasing glucose from the liver through stimulation of A3ARs.
Regulation of BCRP/ABCG2 expression by progesterone and 17β-estradiol in human placental BeWo cells
Authors: Wang Honggang , Zhou Lin , Gupta Anshul , Vethanayagam R. Robert , Zhang Yi , Unadkat Jashvant D. , Mao Qingcheng
Published: December 2005

The breast cancer resistance protein (BCRP) is abundant in the placenta and protects the fetus by limiting placental drug penetration. We hypothesize that pregnancy-specific hormones regulate BCRP expression. Hence, we examined the effects of progesterone (P4) and 17β-estradiol (E2) on BCRP expression in the human placental BeWo cells. P4and E2significantly increased and decreased BCRP protein and mRNA, respectively. Likewise, treatment with P4and E2increased and decreased, respectively, fumitremorgin C-inhibitable mitoxantrone efflux activity of BeWo cells. Reduction in BCRP expression by E2was abrogated by the estrogen receptor (ER) antagonist ICI-182,780. However, the progesterone receptor (PR) antagonist RU-486 had no effect on P4-mediated induction of BCRP. P4together with E2further increased BCRP protein and mRNA compared with P4treatment alone. This combined effect on BCRP expression was abolished by RU-486, ICI-182,780, or both. Further analysis revealed that E2significantly decreased ERβ mRNA and strongly induced PRBmRNA in a dose-dependent manner but had no effect on PRAand ERα. P4alone had no significant effect on mRNA of ERα, ERβ, PRA, and PRB. E2in combination with P4increased PRBmRNA, but the level of induction was significantly reduced compared with E2treatment alone. Taken together, these results indicate that E2by itself likely downregulates BCRP expression through an ER, possibly ERβ. P4alone upregulates BCRP expression via a mechanism other than PR. P4in combination with E2further increases BCRP expression, presumably via a nonclassical PR- and/or E2-mediated synthesis of PRB.
LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training
Authors: Sriwijitkamol Apiradee , Ivy John L. , Christ-Roberts Christine , DeFronzo Ralph A. , Mandarino Lawrence J. , Musi Nicolas
Published: December 2005

AMPK is a key regulator of fat and carbohydrate metabolism. It has been postulated that defects in AMPK signaling could be responsible for some of the metabolic abnormalities of type 2 diabetes. In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway. We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARγ coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats. We also examined whether 7 wk of exercise training on a treadmill reversed abnormalities in the AMPK pathway in obese Zucker rats. In the obese rats, AMPK phosphorylation was reduced by 45% compared with lean rats. Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%. In obese rats, phosphorylation of ACC and protein expression of PGC-1α, two AMPK-regulated proteins, tended to be reduced by 50 ( P = 0.07) and 35% ( P = 0.1), respectively. There were no differences in AMPKα1, -α2, -β1, -β2, and -γ3 protein content between lean and obese rats. Training caused a 1.5-fold increase in AMPKα1 protein content in the obese rats, although there was no effect of training on AMPK phosphorylation and the other AMPK isoforms. Furthermore, training also significantly increased LKB1 and PGC-1α protein content 2.8- and 2.5-fold, respectively, in the obese rats. LKB1 protein strongly correlated with hexokinase II activity ( r = 0.75, P = 0.001), citrate synthase activity ( r = 0.54, P = 0.02), and PGC-1α protein content ( r = 0.81, P < 0.001). In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.
Effects of diabetes and insulin on betaine-homocysteineS-methyltransferase expression in rat liver
Authors: Ratnam Shobhitha , Wijekoon Enoka P. , Hall Beatrice , Garrow Timothy A. , Brosnan Margaret E. , Brosnan John T.
Published: December 2005

Elevation of plasma homocysteine levels has been recognized as an independent risk factor for the development of cardiovascular disease, a major complication of diabetes. Plasma homocysteine reflects a balance between its synthesis via S-adenosyl-l-methionine-dependent methylation reactions and its removal through the transmethylation and the transsulfuration pathways. Betaine-homocysteine methyltransferase (BHMT, EC 2.1.1.5 ) is one of the enzymes involved in the remethylation pathway. BHMT, a major zinc metalloenzyme in the liver, catalyzes the transfer of methyl groups from betaine to homocysteine to form dimethylglycine and methionine. We have previously shown that plasma homocysteine levels and the transsulfuration pathway are affected by diabetes. In the present study, we found increased BHMT activity and mRNA levels in livers from streptozotocin-diabetic rats. In the rat hepatoma cell line (H4IIE cells), glucocorticoids (triamcinolone) increased the level and rate of BHMT mRNA synthesis. In the same cell line, insulin decreased the abundance of BHMT mRNA and the rate of de novo mRNA transcription of the gene. Thus the decreased plasma homocysteine in various models of diabetes could be due to enhanced homocysteine removal brought about by a combination of increased transsulfuration of homocysteine to cysteine and increased remethylation of homocysteine to methionine by BHMT.
SUMO-1, human male germ cell development, and the androgen receptor in the testis of men with normal and abnormal spermatogenesis
Authors: Vigodner Margarita , Ishikawa Tomomoto , Schlegel Peter N. , Morris Patricia L.
Published: December 2005

Sumoylation affects multiple cellular events, including chromatin inactivation and transcriptional repression. Our data provide the first characterization of small ubiquitin-related modifier-1 (SUMO-1) expression during human spermatogenesis by the use of high-resolution cellular SUMO-1 bioimaging. During human meiotic prophase, SUMO-1 localizes to sex chromosomes and centromeric and pericentromeric chromatin. As human spermatocytes progress toward the end of prophase in meiosis I, SUMO-1 is no longer detected within the sex body and pericentromeric heterochromatin but localizes exclusively to centromeres. SUMO-1 localization along sex chromosome axes, pseudoautosomal region, and centromeres of both chromosomes supports a role for SUMO-1 sumoylation in epigenetic events occurring over the entire sex body, e.g., meiotic sex chromosome inactivation and chromatin condensation. Centromeric SUMO-1 throughout meiotic prophase suggests a role in centromeric chromatin condensation and/or other centromere/kinetochore functions. SUMO-1 is likely involved in both facultative and constitutive heterochromatin processes in spermatocytes. Haploid round spermatids show a consistent association of SUMO-1 with centromeric clusters. During spermatid elongation, SUMO-1 localizes in the manchette perinuclear ring. Steroidogenic Leydig cells show some cytoplasmic but strong nuclear and perinuclear SUMO-1. Peritubular myoepithelial cell SUMO-1 colocalizes with centromeric heterochromatin. In epithelial Sertoli cells, when associated with centromeric heterochromatin, SUMO-1 is adjacent but not colocalized with the nucleolus. Male germ cells demonstrate no SUMO-1 nucleolar association. Human and rodent Sertoli cells consistently show an inverse correlation between androgen receptor (AR) and SUMO-1 expression and compartmentalization. Sertoli cells from certain infertile patients, however, showed greatly decreased SUMO-1 and AR. Our data suggest that human testicular SUMO-1 has specific functions in heterochromatin organization, meiotic centromere function, and gene expression.
The immunophilin FKBP52 inhibits the activity of the epithelial Ca2+channel TRPV5
Authors: Gkika Dimitra , Topala Catalin N. , Hoenderop Joost G. J. , Bindels René J. M.
Published: December 2005

In the kidney, the epithelial Ca2+channel TRPV5 constitutes the apical entry pathway in the process of active Ca2+reabsorption. The regulation of Ca2+influx through TRPV5 is of crucial importance, because it determines the final amount of Ca2+excreted in the urine. The present study identifies FKBP52 as an auxiliary protein of TRPV5, inhibiting channel activity. FKBP52 shows specific interaction with TRPV5, and both proteins colocalize in the distal part of the nephron. On the functional level, FKBP52 decreases Ca2+influx through TRPV5 as demonstrated in radioactive45Ca2+uptake measurements and electrophysiological studies in TRPV5-overexpressing human embryonic kidney 293 cells. On the other hand, gene silencing of FKBP52 or administration of the FKBP52 blocker FK-506 enhances Ca2+influx through TRPV5. The inhibitory action of FKBP52 on TRPV5 activity is blunted by mutation of its peptidyl-propyl cis- trans isomerase domain, showing that the FKBP52 catalytic property is critical for channel activity. In conclusion, these results suggest that FKBP52 plays an important role in the regulation of TRPV5 and thus in the process of Ca2+reabsorption.
Temporal Correlations in Stochastic Models of Double Bursting During Simulated Locomotion
Authors: Boothe David L. , Cohen Avis H. , Troyer Todd W.
Published: December 2005

The output of the spinal central pattern generator for locomotion falls into two broad categories: alternation between antagonistic muscles and double bursting within muscles acting on multiple joints. We first model an alternating half-center and then present two different models of double bursting. The first double-bursting model consists of a central clock with an explicit one-to-one mapping between interneuron activity and model output. The second double-bursting model consists of a half-center with an added feedback neuron. Models are built using rate-coded leaky integrator neurons with slow self-inhibition. Structure-function relationships are explored by the addition of noise. The interaction of noise with the dynamics of each network creates a unique pattern of correlation between phases of the simulated cycle. The effects of noise can be explained by perturbation of deterministic versions of the networks. Three basic results were obtained: slow self-inhibitory currents lead to correlations between parts of the step cycle that are separated in time and network relative; model outputs are most sensitive to perturbations presented just before competitive switches in network activity, and clock-like models possess substantial symmetries within the correlation structure of burst durations, whereas the correlation structure of feedback models are asymmetric. Our models suggest that variability in burst length durations can be analyzed to make inferences about the structure of the spinal networks for locomotion. In particular, correlation patterns within double-bursting outputs may yield important clues regarding the interaction between more central, clock-like networks and feedback from more peripheral interneurons.
Enhancement of Excitatory Synaptic Transmission in Spiny Neurons After Transient Forebrain Ischemia
Authors: Zhang Yuchun , Deng Ping , Li Yan , Xu Zao C.
Published: December 2005

Spiny neurons in the neostriatum are highly vulnerable to ischemia. Enhancement of excitatory synaptic transmissions has been implicated in ischemia-induced excitotoxic neuronal death. Here we report that evoked excitatory postsynaptic currents in spiny neurons were potentiated after transient forebrain ischemia. The ischemia-induced potentiation in synaptic efficacy was associated with an enhancement of presynaptic release as demonstrated by an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and a decrease in the paired-pulse ratio. The amplitude of inward currents evoked by exogenous application of glutamate did not show significant changes after ischemia, suggesting that postsynaptic mechanism is not involved. The ischemia-induced increase in mEPSCs frequency was not affected by blockade of voltage-gated calcium channels, but it was eliminated in the absence of extracellular calcium. Bath application of ATP P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) significantly reduced mEPSC frequency in ischemic neurons but had no effects on the control ones. Furthermore, the inhibitory effect of PPADS on ischemic neurons was abolished in Ca2+-free external solution. These results indicate that excitatory synaptic transmissions in spiny neurons are potentiated after ischemia via presynaptic mechanisms. Activation of P2X receptors and the consequent Ca2+ influx might contribute to the ischemia-induced facilitation of glutamate release.
Role of strain differences on host resistance and the transcriptional response of macrophages to infection withYersinia enterocolitica
Authors: van Erp Katrin , Dach Kristina , Koch Isabel , Heesemann Jürgen , Hoffmann Reinhard
Published: December 2005

The outcome of a host-pathogen encounter is determined by virulence factors of the pathogen and defense factors of the host. We characterized the impact of host factors [resistant (C57BL/6) or susceptible (BALB/c) genetic background and exposure to interferon (IFN)-γ] on transcriptional responses of bone marrow-derived macrophages (BMDM) to infection with Yersinia enterocolitica. IFN-γ treatment more profoundly altered the transcriptome of BMDM than did bacterial infection or genetic background. In BALB/c BMDM, 1,161 genes were differentially expressed in response to Yersinia infection with or without IFN-γ prestimulation. Fourteen genes (1.2%) could only be induced by BALB/c BMDM in response to Yersinia infection after IFN-γ pretreatment. These genes inhibit apoptosis, activate NF-κB and Erk signaling, are chemotactic to neutrophils, and are involved in cytoskeletal reorganization, hence possibly in phagocytosis. Ten of these genes possess a common module of binding sites for Hox, Pou, and Creb transcription factors in 2 kb of upstream genomic sequence, suggesting a possible novel role of these transcription factors in regulation of immune responses. Fifty-two of one thousand fifty differentially expressed genes (4.9%) were induced more strongly by C57BL/6 BMDM in response to Yersinia infection than BALB/c BMDM. These genes activate NK cells, have antibacterial properties, or are involved in sensing chemokines and lipopolysaccharide (LPS). These data show that host resistance factors modulate a surprisingly small, but identifiable and functionally significant, portion of the macrophage transcriptome in response to Yersinia infection.
Neutrophil Apoptosis, Activation and Anti-Inflammatory Cytokine Response in Granulocyte Colony-Stimulating Factor-Treated Patients with Community-Acquired Pneumonia
Authors: Droemann D. , Hansen F. , Aries S.P. , Braun J. , Zabel P. , Dalhoff K. , Schaaf B.
Published: December 2005

Background:Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus. Objectives: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP. Methods: Patients received a single dose of G-CSF (1 × 300 or 480 µg s.c.) prior to standard antibiotic treatment (n = 8) or standard treatment only (n = 8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessedusing fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA. Results: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6 ± 9.7 vs. 71.2 ± 17.7, p < 0.01), neutrophil apoptosis decreased (apoptosis: 1.36 ± 0.27 vs. 0.2 ± 0.12%, p < 0.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4 ± 72.2 vs. 340.1 ± 194.6 ng/ml, p < 0.01; sTNF-p55 382 ± 4,243 vs. 632 ± 4,714 ng/ml, p < 0.01; control group nonsignificant). These effects were not seen in the control group. Conclusions: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.
The Future of U.S.-China Relations: Is Conflict Inevitable?
Authors: Friedberg Aaron L.
Published: December 2005

What is likely to be the future character of the relationship between the United States and the People's Republic of China? Will it be marked by convergence toward deepening cooperation, stability, and peace or by deterioration that leads to increasingly open competition and perhaps even war? The answers to these questions are of enormous importance. They are also, at this point, unknown. Most analysts who write on U.S.-China relations deploy arguments derived from the three main camps in contemporary international relations theorizing: realism, liberalism, and constructivism. Those whose basic analytical premises place them in one of these three schools, however, do not necessarily have similar views regarding the speciac question of the future of U.S.-China relations. It is possible to identify realists who believe that the relationship will basically be stable and peaceful, liberals who expect confrontation and confict, and constructivists who think that things could go either way. The six basic positions in this debate all rest on claims about the importance of particular causal mechanisms or sets of similarly aligned causal forces. In reality, one set of forces may turn out to be so powerful as to overwhelm the rest. But it is also conceivable that the future will be shaped by a confuence of different forces, some mutually reinforcing and others opposed.