bluuebunny/crossref_metadata_2025 huggingface dataset:
The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis are directly regulated by estrogen receptor
Authors: Watanabe H , Takahashi E , Kobayashi M , Goto M , Krust A , Chambon P , Iguchi T
Published: February 2006

Recent studies have revealed that hundreds of genes in the uterus are activated by estrogen. Their expression profiles differ over time and doses and it is not clear whether all these genes are directly regulated by estrogen via the estrogen receptor. To select the genes that may be regulated by estrogen, we treated mice with several doses of estrogen and searched for those genes whose dose–response expression pattern mirrored the uterine growth pattern. Among those genes, we found that the dose-dependent expression of the adrenomedullin (ADM) gene correlated well with the uterotrophic effect of estrogen. ADM expression is induced early after estrogen administration and is restricted to the endometrial stroma. The spatiotemporal gene expression pattern of ADM was similar to that of receptor-modifying protein 3 (RAMP3). RAMP3 is known to modify calcitonin gene-related receptor (CRLR) so that it can then serve as an ADM receptor. Chromatin immunoprecipitation assays indicated that the estrogen receptor binds directly to the ADM promoter region and RAMP3 intron after estrogen administration. It was also shown that neither the ADM nor RAMP3 gene could be activated in estrogen receptor-α-null mouse. Although uterine ADM expression has been reported to occur in the myometrium, our observations indicate that estrogen-induced ADM is also expressed in the uterine stroma and that such variable, spatiotemporally regulated ADM expression contributes to a wider range of biological effects than previously expected.
Neurohypophysial dysmorphogenesis in mice lacking the homeobox gene Uncx4•1
Authors: Asbreuk C H J , van Doorninck J H , Mansouri A , Smidt M P , Burbach J P H
Published: February 2006

A number of transcription factors have been implicated in the development of the hypothalamo-neurohypophysial system (HNS). Null mutations for these factors caused severe defects in proliferation, migration and survival during early embryogenesis. While they have informed about early events of HNS developments no insights in mechanisms of late development and maturation of this major peptidergic system have been obtained as yet. In a screen for adult-expressed homeobox genes we identified Uncx4.1 as a gene expressed in adult and embryonic magnocellular neurons of the (HNS). Null mutation of Uncx4.1 left these neurons viable and able to express neuropeptides. However, the connectivity of magnocellular neurons with posterior pituitary elements was compromised. As a consequence neuronal fibres traversed to the adenohypophysis. The penetrance of this phenotype was about 50%. The data show a selective role of Uncx4.1 in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and to deliver hormones for control of peripheral functions.
Identification and characterization of a novel isoform of the vesicular γ-aminobutyric acid transporter with glucose-regulated expression in rat islets
Authors: Suckow A T , Sweet I R , Van Yserloo B , Rutledge E A , Hall T R , Waldrop M , Chessler S D
Published: February 2006

Pancreatic islets are unique outside the nervous system in that they contain high levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), synthesized by the enzyme glutamic acid decarboxylase (GAD). Since the role that GABA plays in the islet and the mechanisms whereby the two major GAD isoforms (GAD65 and GAD67) function as diabetes-associated autoantigens are unknown, continued characterization of the islet GAD–GABA system is important. We previously demonstrated that the GABA and glycine transporter vesicular inhibitory amino acid transporter (VIAAT also known as VGAT) is present in rat islets. Here we identify a novel 52 kDa variant of VIAAT in rat islets: VIAAT-52 (V52). V52 is an amino-terminally truncated form of VIAAT (V57) that likely results from utilization of a downstream start site of translation. V57 and V52 display different patterns of post-translational modification and cellular expression. Our results have indicated that islet content of V52, but not V57, is responsive to changes in glucose concentration and other extracellular conditions. VIAAT is expressed in the islet α cells, but there have been conflicting findings regarding the presence of VIAAT in the β cells. Here we have also provided additional evidence for the presence of VIAAT in islet β cells and show that the β cell line INS-1 expresses V57. V52 may be better adapted than V57 to the unique rat α cell GAD–GABA system, which lacks GAD65 and in which VIAAT traffics to secretory granules rather than just to synaptic microvesicles.
The appetite suppressant d-fenfluramine reduces water intake, but not food intake, in activity-based anorexia
Authors: Hillebrand J J G , Heinsbroek A C M , Kas M J H , Adan R A H
Published: February 2006

Biochemical, genetic and imaging studies support the involvement of the serotonin (5-HT) system in anorexia nervosa. Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa, and combines scheduled feeding with voluntary running wheel activity (RWA). We investigated the effect of d-fenfluramine (d-FEN) treatment on development and propagation of ABA. d-FEN is an appetite suppressant and acts on 5-HT2C receptors that are located on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. Since stimulation activation of the melanocortin system stimulates ABA, we hypothesized that d-FEN treatment enhances the development and propagation of ABA. Rats were exposed to the ABA model and chronically infused with d-FEN. Unexpectedly, d-FEN-treated ABA rats did not reduce food intake or increase wheel running as compared with vehicle-treated ABA rats. Furthermore d-FEN treatment did not affect body weight loss, hypothalamus-pituitary-adrenal axis activation, or starvation-induced hypothermia in ABA rats. POMC mRNA levels in d-FEN-treated rats were not different from vehicle-treated rats after one week of exposure to the ABA paradigm. However, d-FEN-treated ABA rats showed hypodypsia and increased plasma osmolality and arginine-vasopressin expression levels in the hypothalamus. We conclude that d-FEN treatment does not enhance ABA under the experimental conditions of this study, but strongly reduces water intake in ABA rats.
Transcriptional regulation of the rat apelin receptor gene: promoter cloning and identification of an Sp1 site necessary for promoter activity
Authors: O’Carroll Anne-Marie , Lolait Stephen J , Howell Gillian M
Published: February 2006

The genomic structure and transcriptional regulation of the rat apelin receptor (APJR) were analysed by rapid amplification of 5′ cDNA ends (5′-RACE), transient expression assays and DNA–protein interaction. Analysis of the 5′-flanking region of a rat genomic clone shows no TATA box, but a putative CAAT box and several putative binding sites for transcription factors are present. Two transcriptional start sites were identified by 5′-RACE, RNase protection and primer extension analyses. Promoter activity was exhibited in the APJR- expressing SH-SY5Y cell line as well as in COS-7 and Chinese hamster ovary (CHO-K1) cells. Consecutive 5′-deletion analysis revealed the highest promoter activity in a region between bp −966 and −165. DNaseI footprint analysis revealed seven protected regions and electrophoretic mobility shift, super-shift and competition assays identified individual DNA–protein complexes capable of binding Sp1, estrogen receptor (ER)α, glucocorticoid receptor and CCAAT enhancer binding protein (C/EBP)γ transcription factors. Site-directed mutagenesis identified an individual Sp1 motif that plays a major role in activation of the APJR promoter and also demonstrated constitutive transcriptional regulation of the promoter by estrogen and glucocorticoid receptors. Promoter regulation by the cAMP-dependent signal cascade was also shown.
New insights into growth hormone action
Authors: Waters M J , Hoang H N , Fairlie D P , Pelekanos R A , Brown R J
Published: February 2006

It has been 75 years since Evans and Long identified a somatic growth-promoting substance in pituitary extracts, yet it is only in the last 20 years that the molecular basis for this action has been established. Three key elements in this elucidation were the cloning of the GH receptor, the identification of Janus kinase (JAK) 2 as the receptor-associated tyrosine kinase, and the delineation of signal transduction and activators of transcription (STAT) 5a/b as the key transcription factor(s) activated by JAK2. The interaction between these three elements results in enhanced postnatal growth and is the subject of this review. We describe a new model for GH receptor activation based on subunit rotation within a constitutive dimer, together with the phenotype and hepatic transcript profile of mice with targeted knockins to the receptor cytoplasmic domain. These support a central role for STAT5a/b in postnatal growth.
The co-existence of two growth hormone receptors in teleost fish and their differential signal transduction, tissue distribution and hormonal regulation of expression in seabream
Authors: Jiao Baowei , Huang Xigui , Chan Chi Bun , Zhang Li , Wang Deshou , Cheng Christopher H K
Published: February 2006

Two genomic contigs of putative growth hormone receptors (GHRs) were identified in fugu and zebrafish genomes by in silico analysis, suggesting the presence of two GHR subtypes in a single teleost species. We have tested this hypothesis by cloning the full-length cDNA sequence of a second GHR subtype from the black seabream in which the first GHR subtype had been previously reported by us. In addition, we had also cloned the sequences of both GHR subtypes from two other fish species, namely the Southern catfish and the Nile tilapia. Phylogenetic analysis of known GHR sequences from various vertebrates revealed that fish GHRs cluster into two distinct clades, viz. GHR1 and GHR2. One clade (GHR1), containing 6 to 7 extracellular cysteine residues, is structurally more akin to the non-teleost GHRs. The other clade (GHR2), containing only 4 to 5 extracellular cysteine residues, is unique to teleosts and is structurally more divergent from the non-teleost GHRs. In addition, we had examined the biological activities of both GHR subtypes from seabream using a number of reporter transcription assays in cultured eukaryotic cells and demonstrated that both of them were able to activate the Spi 2.1 and β-casein promoters upon receptor stimulation in a ligand specific manner. In contrast, only GHR1 but not GHR2 in seabream could trigger the c-fos promoter activity, indicating that the two GHR subtypes possess some differences in their signal transduction mechanisms. Also, the expression of GHR2 is significantly higher than GHR1 in many tissues of the seabream including the gonad, kidney, muscle, pituitary and spleen. In vivo hormone treatment data indicated that cortisol upregulated hepatic GHR1 expression in seabream but not GHR2, whereas testosterone decreased hepatic GHR2 expression but not GHR1. On the other hand, hepatic expression of both GHR1 and GHR2 in seabream was decreased by estradiol treatment.
Acute regulation of murine follicle-stimulating hormone β subunit transcription by activin A
Authors: Lamba Pankaj , Santos Michelle M , Philips Daniel P , Bernard Daniel J
Published: February 2006

In rodents, activins stimulate immediate-early increases in pituitary follicle-stimulating hormone β (Fshb) subunit transcription. Here, we investigated the underlying signaling mechanisms using the mouse gonadotrope cell line, LβT2. Activin A increased mouse Fshb-luciferase reporter activity within 4 h through a Smad-dependent signaling pathway. The ligand rapidly stimulated formation of SMAD2/3/4 complexes that could interact with a consensus palindromic Smad binding element (SBE) in the proximal Fshb promoter. SMAD over-expression potently stimulated transcription, with the combination of SMADs 2, 3 and 4 producing the greatest synergistic activation. A mutation in the SBE that abolished Smad binding greatly impaired the effects of acute (4 h) activin A treatment and SMAD over-expression on promoter activity, but did not abolish the effects of chronic (24 h) activin A exposure. Within activated SMAD complexes, SMADs 3 and 4 appeared to bind the SBE simultaneously and the binding of both was required for maximal transcriptional activation. Interestingly, the human FSHB promoter, which lacks the consensus SBE, was neither rapidly stimulated by activin A nor by over-expressed SMADs, but was activated by 24 h activin A. Addition of the SBE to the human promoter increased both SMAD2/3/4-sensitivity and acute regulation by activin A, though not to levels observed in mouse. We postulate that short reproductive cycles in female rodents, particularly the brief interval between the primary and secondary FSH surges of the estrous cycle, require the Fshb promoter in these animals to be particularly sensitive to the rapid, Smad-dependent actions of activins on transcription. The human FSHB promoter, in contrast, is chronically regulated by activins seemingly through a SMAD-independent pathway.
Collagenases in Gingival Crevicular Fluid in Type 1 Diabetes Mellitus
Authors: Safkan‐Seppälä Bedia , Sorsa Timo , Tervahartiala Taina , Beklen Arzu , Konttinen Yrjö T.
Published: February 2006

Background: Studies have demonstrated that high levels of collagenase activity in gingival crevicular fluid (GCF) are associated with degradation of periodontal tissues in progressive periodontitis compared to periodontally healthy tissues. Because the activation of collagenases is an important issue in periodontitis, we have studied the activation of collagenase in gingival crevicular fluid samples of diabetic patients.

Methods: Collagenase activity was studied in human gingival crevicular fluids. Twenty‐two poorly controlled diabetic patients (e.g., blood glucose: 11.0 ± 0.7 mmol/l; hemoglobin A1c [HbA1c]: 9.6% ± 0.3%) and five well‐controlled diabetic patients were compared to six chronic periodontitis subjects and five healthy controls. Collagenase activity against type I collagen was measured using sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis quantitated by laser densitometry.

Results: The poorly controlled diabetic patients had more alveolar bone loss than the well‐controlled diabetic subjects and controls (P <0.001; t test). The activity of collagenases in GCF in poorly controlled diabetic patients was similar to that seen in chronic periodontitis subjects (P >0.05) but higher than in healthy controls (P <0.01; t test), whereas there was no difference between the well‐controlled diabetic subjects and systemically healthy controls (P >0.05; t test).

Conclusion: Poorly controlled diabetes is strongly related to periodontal tissue destruction, and collagenases in GCF may mediate and reflect this effect.
Compliance as a Prognostic Indicator: Retrospective Study of 505 Patients Treated and Maintained for 15 Years
Authors: Miyamoto Takanari , Kumagai Takashi , Jones Judith A. , Van Dyke Thomas E. , Nunn Martha E.
Published: February 2006

Background: The relationship of patient compliance to overall tooth prognosis remains controversial. There are little data, often conflicting, that pertain to tooth loss as a function of patient compliance.

Methods: This retrospective study evaluates the impact of compliance (complete versus erratic) on common periodontal clinical variables, such as probing depth, bleeding index, plaque index, and tooth loss for 505 patients in a long‐term period of observation (15 to 23 years) and maintenance therapy (at least 10 years). Compliance was defined in two ways for all analyses. Under the definition for compliance 1, patients who missed <30% of all prescribed maintenance visits were classified as complete compliers. Under the definition for compliance 2, patients who never went 2 years without a maintenance visit were classified as complete compliers. Change in clinical variables was dichotomized into reduction in plaque index versus no reduction, reduction in bleeding on probing versus no reduction, reduction in the percentage of periodontal pockets >3 mm versus no reduction, no increase in decayed, missing, or filled teeth (DMFT) versus increase, and no tooth loss versus tooth loss. The effects of both definitions of compliance were then evaluated in a series of multiple logistic regression models with adjustment for potential confounders.

Results: The analysis of the dichotomous change in clinical parameters over time revealed that complete compliers tended to show reduction in bleeding on probing and reduction in plaque index compared to erratic compliers for both definitions of compliance. In contrast, complete compliers under compliance 2 were less likely to have a reduction in the percentage of periodontal pockets >3 mm compared to erratic compliers, whereas complete compliers under compliance 1 had about the same likelihood of demonstrating a reduction in periodontal pockets compared to erratic compliers under this classification scheme. Under both definitions for compliance, complete compliers were more likely to exhibit tooth loss than erratic compliers, with the greatest tooth loss exhibited by complete compliers under the definition for compliance 1.

Conclusions: Based on these results, complete compliers under both definitions tended to show a reduction in plaque and bleeding on probing over time. However, change in periodontal pockets and DMFT over time varied according to the definition of compliance that was used. In addition, the results seem to indicate that the decision for tooth extraction made by dental health professionals at maintenance visits may result in greater tooth loss.
Peri‐Implant Bone Organization Under Immediate Loading State. Circularly Polarized Light Analyses: A Minipig Study
Authors: Neugebauer Jörg , Traini Tonino , Thams Ulf , Piattelli Adriano , Zöller Joachim E.
Published: February 2006

Background: Immediate loading of dental implants is currently one of the most examined topics in implant dentistry. Using screw implants with a microstructured surface and bone‐quality–adapted insertion procedures, osseointegration is achieved when implants are initially stable and when splinted with the superstructure. Despite reported success, there is a shortage of information relating to remodeling and peri‐implant bone formation with immediately loaded implants.

Methods: Four to six immediately loaded and unloaded dental implants with a microstructured surface were placed in the mandible and the maxilla in seven minipigs. A total of 85 implants were placed. After a 4‐month healing period, all implants were retrieved. Histomorphometry was performed using a light microscope in transmitted polarized light connected to a high‐resolution video camera interfaced to a monitor and personal computer. This optical system was associated with a digitizing pad and a histomorphometry software package with image capturing capabilities.

Results: Implants showed osseointegration if the average insertion torque of the implants within one bridge was >35 Ncm. If the primary stability of the bridge was <35 Ncm, all implants in the quadrant were lost after 4 months. The multivariate discriminant analysis showed the highest correlation for implant stability by bridge insertion torque (BIT), localization (mandible or maxilla), and implant insertion torque (IIT) as success parameters. The loaded implants displayed collagen fibers, which were oriented in a more transverse way. In addition, a higher quantity of secondary osteons was present. In comparison, the unloaded implants had collagen fibers with a more parallel orientation, and a higher quantity of marrow spaces was present.

Conclusions: When observed after 4 months, immediately loaded implants showed a higher degree of bone formation and remodeling in comparison to unloaded implants. Immediately loaded implants also demonstrated a prevalence of transversely oriented collagen fibers in the peri‐implant bone. In this animal model, an average insertion torque of the implants within one bridge >35 Ncm was associated with the most successful implants.
Longitudinal Clinical Evaluation of Adjunct Minocycline in the Treatment of Chronic Periodontitis
Authors: Cortelli José Roberto , Querido Silvia Maria Rodrigues , Aquino Davi Romeiro , Ricardo Lucilene Hernandes , Pallos Debora
Published: February 2006

Background: The clinical benefits of minocycline in combination with thorough scaling and root planing (SRP) have been examined in multicenter studies. The aim of this longitudinal investigation was to evaluate the clinical response to scaling and root planing combined with the use of locally delivered minocycline microspheres for 720 days in individuals with advanced chronic periodontitis.

Methods: A total of 26 individuals aged 26 to 69 years (mean: 46.8 ± 12.1 years) were included in this double‐blind randomized clinical trial. After randomization, 13 individuals were selected for the test group (TG) and treated with SRP plus subgingival minocycline at baseline and 90, 180, and 270 days, and 13 individuals were selected for the control group (CG) and received SRP plus vehicle at the same timepoints. Two homologous sites with probing depth (PD) ≥6 mm were chosen in each subject. To evaluate the clinical response after treatment, PD, plaque index (PI), and gingival index (GI) were assessed at baseline and 90, 180, 270, 360, and 720 days.

Results: No statistical differences were found between test and control groups in relation to PD at the different timepoints. The mean values of PD demonstrated a higher reduction in the test group at 270 and 360 days. No statistical differences were observed at 90, 180, and 720 days between TG and CG (P <0.05; Wilcoxon test). There were no statistically significant differences between TG and CG concerning PI and GI (P <0.05; analysis of variance and t test) at all evaluated timepoints.

Conclusion: Our findings demonstrated that both therapies reduced mean PD from 90 to 360 days; however, SRP combined with the use of subgingival minocycline showed a higher reduction at 270 and 360 days following therapy.
Er:YAG Laser Scaling of Diseased Root Surfaces: A Histologic Study
Authors: Crespi Roberto , Barone Antonio , Covani Ugo
Published: February 2006

Background: The aim of the present study was to observe the effects of an erbium‐doped:yttrium, aluminum, and garnet (Er:YAG) laser when used to treat periodontally involved root surfaces.

Methods: Forty teeth affected by severe periodontal disease and scheduled for extraction were divided into two groups: in group A (control), 20 teeth were treated by hand instrumentation, and in group B (test), 20 teeth were treated by Er:YAG laser.

Results: In group A (teeth treated by curets), the root cementum layer was completely removed, but many deep scratches on the dentin layer were also observed. In group B, the laser‐treated root surfaces, there was no cracking or carbonization, and the bacterial flora was completely eliminated, leaving a rough and uniform surface.

Conclusion: Results of the present study showed that clinical use of an Er:YAG laser in vivo achieves plaque and calculus removal, providing a rough surface morphology.
Periodontal and Hematological Characteristics Associated With Aggressive Periodontitis, Juvenile Idiopathic Arthritis, and Rheumatoid Arthritis
Authors: Havemose‐Poulsen Anne , Westergaard Jytte , Stoltze Kaj , Skjødt Henrik , Danneskiold‐Samsøe Bente , Locht Henning , Bendtzen Klaus , Holmstrup Palle
Published: February 2006

Background: Periodontitis shares several clinical and pathogenic characteristics with chronic arthritis, and there is some degree of coexistence. The aims of this study were to elucidate whether patients with localized aggressive periodontitis (LAgP), generalized aggressive periodontitis (GAgP), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA) share periodontal and hematological characteristics distinguishing them from individuals free of diseases.

Methods: The study population consisted of white adults (≤35 years old) with LAgP (N = 18), GAgP (N = 27), JIA (N = 10), RA (N = 23), and healthy controls (N = 25). All individuals underwent a standardized interview, blood sampling, and an intraoral examination, including registration of plaque, bleeding on probing, probing depth (PD), clinical attachment loss (CAL), and alveolar bone loss (ABL) on radiographs. Blood samples were analyzed for erythrocyte fraction, leukocytes and differential counts, erythrocyte sedimentation rate, C‐reactive protein (CRP), immunoglobulin (Ig) M and IgA rheumatoid factors (RFs), and antibodies to cyclic citrullinated peptides.

Results: RA patients had a higher percentage of sites with PD ≥4 mm, CAL ≥2 mm, and ABL ≥2 mm compared to controls. The percentage of sites with CAL ≥2 mm significantly correlated with the levels of IgM‐RF and IgA‐RF. Missing teeth in JIA and RA patients were not lost due to periodontitis. Patients with GAgP showed higher levels of leukocytes, including neutrophils, and CRP compared to controls. In part, JIA and RA patients showed similar results.

Conclusions: Young adults with RA may develop periodontal destruction, and these patients require professional attention. Both differences and similarities in periodontal and hematological variables were seen in individuals with periodontitis, JIA, and RA.
Bone Sialoprotein Gene Transfer to Periodontal Ligament Cells May Not Be Sufficient to Promote Mineralization In Vitro or In Vivo
Authors: Hakki Sema S. , Wang Dian , Franceschi Renny T. , Somerman Martha J.
Published: February 2006

Background: To improve regenerative therapies, it is important to understand the cells and factors modulating periodontal tissues. Our group has focused on bone sialoprotein (BSP), a mineralized tissue‐selective protein considered to be involved in the initiation of cementogenesis and osteogenesis. In this study, we examined whether gene transfer of BSP into periodontal ligament (PDL) cells would result in an increased ability of PDL cells to promote mineralization in vitro and in vivo.

Methods: PDL cells obtained from CD‐1 mice were immortalized using simian virus (SV) 40 large T antigen (TAg) and designated SV‐PDL cells. SV‐PDL cells were infected in vitro with LacZ gene‐expressing control adenovirus vector. A 1,000 plaque‐forming unit (pfu) titer was selected (based on X‐gal staining) and cells were infected with mouse BSP‐expressing replication‐deficient adenoviral vector to determine the mRNA expression and protein level of BSP. Total RNA was isolated from cells on days 2, 4, and 6. Media were obtained on days 3, 5, and 7 for protein determination. Northern blot analysis was performed for mRNA expression and Western blot analysis for protein expression. To test the effect of BSP gene transfer on the mineralization of PDL cells, in vitro (von Kossa) and in vivo (severe combined immunodeficiency [SCID] mice) experiments were performed.

Results: Under normal conditions, PDL cells do not express BSP transcripts and do not promote significant mineralization. SV‐PDL cells infected with a BSP viral vector expressed and secreted substantial levels of BSP as confirmed by Northern and Western blot analysis. BSP mRNA and protein levels were strong on day 2 and still apparent on day 6, although not as great. However, no mineral nodule formation was noted either in vitro or in vivo.

Conclusions: Although BSP is an important and necessary protein for mineralization, it may not be sufficient for promoting mineralization without the addition or removal of other factors. Further studies will help to clarify the specific factors required for promoting mineralization, a required step for designing predictable periodontal regenerative therapies.
Phenotypic Study of Human Gingival Fibroblasts Labeled With Superparamagnetic Anionic Nanoparticles
Authors: Naveau Adrien , Smirnov Pierre , Ménager Christine , Gazeau Florence , Clément Olivier , Lafont Antoine , Gogly Bruno
Published: February 2006

Background: A specific labeler of the human gingival fibroblast (HGF) does not exist. Anionic maghemite nanoparticles allow labeling of a wide cell variety and their recognition in cellular, organotypical, and animal models.

Methods: We studied internalization effects of nanoparticles on an HGF phenotype in vitro, evaluating transcription and secretion of connective tissue remodeling molecules, i.e., matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines controlling their activation/inhibition, i.e., transforming growth factor‐β (TGF‐β1), tumor necrosis factor‐α (TNF‐α), and interleukins 1β and 4 (IL‐1β and IL‐4). After proliferation kinetics, cellular uptake was studied by Perls coloration and magnetophoresis on labeled culture. Dot blotting, Western blotting, and zymography were used to detect MMP‐1, ‐2, and ‐3 and TIMP‐1 and ‐2 secretions in culture supernatants, and reverse transcription‐polymerase chain reaction (RT‐PCR) was performed to detect the mRNA expression of these molecules. Enzyme‐linked immunosorbent assay (ELISA) tests were used to determine TGF‐β1, TNF‐α, IL‐1β, and IL‐4 levels.

Results: Our data indicated high (15.3 ± 5.8 pg/cell) but heterogeneous distribution of nanoparticles in HGF. Twenty‐four hours after labeling, MMP‐1, ‐2, and ‐3 and TIMP‐2 secretion increased (P <0.001) with RT‐PCR confirmation at 12 hours, whereas TIMP‐1 did not. IL‐1β increased at day 1 (D1) (P <0.001) and IL‐4 at D3 (P <0.01), but not TGF‐β1 or TNF‐α.

Conclusions: After labeling with these maghemite nanoparticles, HGF increased secretion of IL‐1β at D1, probably inducing the increase of MMP‐1, ‐2, and ‐3 and TIMP‐2. The increase of IL‐4 secretion began with the decreased synthesis of MMPs and TIMPs at D3. Despite this transitory inflammatory reaction at 3 days following internalization, maghemite nanoparticles did not affect HGF phenotype, thereby authorizing their use as labelers.
Increased Intake of Dairy Products Is Related to Lower Periodontitis Prevalence
Authors: Al‐Zahrani Mohammad S.
Published: February 2006

Background: An inverse association between calcium intake and periodontitis prevalence was recently reported. Dairy products are rich sources of calcium and other important nutrients. To date, it appears that the relationship between the intake of dairy products and periodontitis has not been investigated. The purpose of the present study was to examine whether or not there is an association between the intake of dairy products and periodontitis prevalence.

Methods: A total of 12,764 individuals who participated in the Third National Health and Nutrition Examination Survey were included in this study. Individuals who had at least one site with an attachment loss ≥3 mm and a probing depth ≥4 mm were considered to have periodontitis. The intake of dairy products was categorized into quintiles. Descriptive statistics and logistic regression models were used for data analyses.

Results: Prevalence of periodontitis was 41% lower for individuals in the highest quintile of intake of dairy products than those in the lowest quintile (P <0.001 for trend). After adjusting for known and suspected periodontitis risk factors (age, gender, race\ethnicity, cigarette smoking, education, diabetes, poverty index, vitamin use, body mass index, physical activity, time since the last dental visit, dental calculus, and gingival bleeding), individuals in the highest quintile of intake of dairy products were 20% less likely to have periodontitis than those in the lowest quintile (P = 0.024 for trend).

Conclusions: The results of this study showed an inverse association between the intake of dairy products and prevalence of periodontitis. Longitudinal and/or intervention studies are required to confirm these findings and to further examine the impact of a higher intake of dairy products on the prevention and treatment of periodontitis.
Characterization of Patients Presenting for Treatment to a University Refractory Periodontal Diseases Unit: Three Case Reports
Authors: Bhide Vinay M. , Tenenbaum Howard C. , Goldberg Michael B.
Published: February 2006

Background: Of the many forms of periodontal disease, refractory periodontal diseases are the least characterized. They are defined as the continued degeneration of the periodontium despite adequate management. This has led to the suggestion that there may be a systemic component that is a contributing factor to the development of this condition. The objectives of this report were to follow the progression of clinical changes associated with periodontal disease over a number of years in this unique population and review various hematologic and microbiologic factors that may be contributing to the disease progression.

Methods: Three subjects were profiled. They were referred to the Refractory Periodontal Disease Unit at the University of Toronto by periodontists or general practitioners in the Southern Ontario region. Complete medical and dental histories were obtained along with baseline clinical measurements. Periodontal examinations were facilitated with the use of a computer‐assisted periodontal probe. A microbiologic analysis using immunofluorescence techniques was able to detect Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Actinobacillus actinomycetemcomitans and spirochetes. A hematologic analysis, including a complete blood count (CBC), immune profile, and glycosylated hemoglobin assay, was also performed.

Results: The clinical presentation revealed that patients receiving adequate maintenance therapy and with good to excellent oral hygiene demonstrated sites with continual loss of attachment. Few periodontal pathogens were detected. However, the most significant finding appeared to be the report elevated levels of CD8+ cells within this group of patients compared to normal laboratory ranges.

Conclusions: This report is an attempt at characterizing a unique population within the periodontal realm. The long‐term monitoring of these patients allowed for an assessment of factors that may be involved in the continued decline of the periodontal health of these patients. Based on the immune profile, it is possible that a hyperresponsive state may be the primary feature of this population. Future assessments, including full‐mouth interleukin (IL)‐1 and matrix metalloproteinase (MMP)‐8 levels, may assist in characterizing this population further, with the goal of producing markers that will assist clinicians in predicting treatment outcome.
The Effects of Antimicrobial Sprays and Mouthrinses on Supragingival Plaque Regrowth: A Comparative Study
Authors: Pizzo Giuseppe , Guiglia Rosario , Imburgia Mario , Pizzo Ignazio , D'Angelo Matteo , Giuliana Giovanna
Published: February 2006

Background: Due to the side effects of chlorhexidine digluconate (CHX) mouthrinsing, a spray has been proposed as an alternative method of CHX delivery to the oral cavity. The aim of this study was to investigate the plaque inhibitory effects of CHX, cetylpyridinium chloride (CPC), and triclosan (TRN) delivered by sprays and mouthrinses.

Methods: The study was an observer‐masked, randomized cross‐over design balanced for carryover effects, involving 15 healthy volunteers in a 4‐day plaque regrowth model. Products being tested (0.2% CHX, 0.12% CHX, 0.05% CPC, and 0.03% TRN) were used both as sprays and mouthrinses. A saline solution served as a negative control. On day 1, subjects received professional prophylaxis, suspended oral hygiene measures, and commenced using their allocated products. On day 5, subjects were scored for disclosed plaque.

Results: CHX sprays (P <0.01) were the most effective sprays in preventing plaque regrowth, without significant differences between the two concentrations tested (P >0.05). TRN spray showed a significant inhibition of plaque regrowth in comparison to the negative control (P <0.05). CPC spray did not differ from saline spray (P >0.05). A similar trend of efficacy was detected for rinses. Although the effect on plaque regrowth observed with CHX rinses was superior to that of CHX sprays (P <0.0003), the latter did not cause side effects (P >0.2).

Conclusions: These findings, together with those from clinical trials, suggest that the CHX‐containing sprays may represent an effective alternative to CHX rinses when mechanical oral hygiene has to be avoided in restricted areas. On the contrary, the TRN and CPC sprays showed little or no plaque inhibitory effects.
Description of Two New Cathepsin C Gene Mutations in Patients With Papillon‐Lefèvre Syndrome
Authors: Wani Aijaz Ahmad , Devkar Nihal , Patole Milind S. , Shouche Yogesh S.
Published: February 2006

Background: Papillon‐Lefèvre syndrome (PLS) is a rare autosomal disorder characterized by severe periodontitis and palmar plantar hyperkeratosis (PPK). PLS is caused by mutations in the cathepsin C (CTSC) gene. Dipeptidyl peptidase I (DPPI) encoded by the CTSC locus removes dipeptides from the amino terminus of the protein substrate and mainly plays an important role in immune and inflammatory processes. Several mutations have been reported in this gene in patients with PLS. This study reports two novel deletion mutation of the CTSC gene in two Indian families with PLS.

Methods: Peripheral blood samples were obtained for genomic DNA isolation from individuals belonging to two Indian families. Exon‐specific intronic primers were used to amplify DNA from all individuals, and the PCR products were subsequently sequenced to detect the mutations. Heteroduplex analysis (HDA) was used to confirm heterozygosity and to determine the presence of mutations in control individuals.

Results: All patients from both families had a classic PLS phenotype, which included PPK and severe periodontitis. Sequence analysis of the CTSC gene revealed two novel deletion mutations, one (1213‐1215delCAT) in exon 7 and the other (629‐630delGA) in exon 4 of the CTSC gene. For both mutations, the patients were homozygous, whereas the parents were heterozygous.

Conclusions: This study reports two novel deletion mutations in two Indian families with PLS. One of the mutations introduces a premature stop codon, thereby producing a truncated protein. In the other case, the mutation observed leads to the loss of a highly conserved histidine molecule that is present in the active site of the enzyme. In both cases, mutations may result in a conformation change, causing loss of the enzymatic activity.
A Systematic Review on the Effects of the Chlorhexidine Chip When Used as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis
Authors: Cosyn Jan , Wyn Iris
Published: February 2006

Background: Several local antimicrobial agents, such as a bioabsorbable chlorhexidine chip, have been developed to enhance the outcome of non‐surgical periodontal therapy.

Methods: Electronic (MEDLINE and Cochrane Oral Health Group Specialized Trials Register) and manual searches were performed to detect studies concerning the use of the chlorhexidine chip as an adjunct to scaling and root planing in the treatment of chronic periodontitis. Only full‐text randomized controlled trials published in English up to June 2005 were included.

Results: Five studies were finally selected following independent screening by two reviewers. Due to considerable heterogeneity in study design, a qualitative data analysis was performed. Multicenter studies have indicated significantly higher pocket reductions and clinical attachment gains following a combination of mechanical debridement and repeated chlorhexidine chip administration in comparison to scaling and root planing alone. However, some recent studies failed to confirm the additional value of the chlorhexidine chip. A number of interstudy disparities with respect to methodological quality and study design may account for this lack of accordance.

Conclusions: The clinical and microbiological data currently available on the chlorhexidine chip are limited and conflicting. More research is needed to elucidate the additional value of the chlorhexidine chip when used as an adjunct to scaling and root planing.
Direct-to-Consumer Drug Company Pharmacies
Authors: Rome Benjamin N.
Published: February 2024

The recent launch of direct-to-consumer pharmacy LillyDirect prompts the author of this Viewpoint to consider why it was created and also to raise concerns about allowing manufacturers to sell their drugs directly to patients.
T2* Mapping of Placental Oxygenation to Estimate Fetal Cortical and Subcortical Maturation
Authors: Nichols Emily S. , Al-Saoud Sarah , de Vrijer Barbra , McKenzie Charles A. , Eagleson Roy , de Ribaupierre Sandrine , Duerden Emma G.
Published: February 2024

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.
Genome-Wide Interaction Study of Dietary Intake and Colorectal Cancer Risk in the UK Biobank
Authors: Hoang Tung , Cho Sooyoung , Choi Ji-Yeob , Kang Daehee , Shin Aesun
Published: February 2024

Importance

Candidate gene analysis approaches have shown that colorectal cancer (CRC) risk attributable to diet may differ according to genotype. A genome-wide approach further allows for the exploration of underlying pathways for associations between diet and CRC risk across the genome.

Objectives

To identify genetic variants that modify diet-CRC associations and to further explore the underlying pathways in the cause of CRC.

Design, Setting, and Participants

This nested case-control study used data on White British participants from the prospective cohort UK Biobank. Participants were recruited between March 13, 2006, and October 1, 2010, and data were censored June 25, 2021.

Exposures

The average frequency intake of 11 dietary factors in the year preceding baseline was obtained via a touchscreen questionnaire. After quality control for more than 93 million variants of imputed genetic data, 4 122 345 variants remained.

Main Outcomes and Measures

Colorectal cancer cases were identified according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Genome-wide interaction analysis was performed to test interactions between dietary factors and variants using a conditional logistic regression model. Summary statistics of interactions at the variant level were used to calculate empirical P values for interactions at gene and gene-set levels in gene-based and gene-set enrichment analyses.

Results

A total of 4686 participants with CRC (mean [SD] age, 60.7 [6.6] years; 2707 men [57.8%]) received a new diagnosis during a median of 12.4 years (IQR, 11.6-13.1 years) of follow-up. Once a case was detected, 3 matched controls were identified, for a total of 14 058 controls (mean [SD] age, 60.4 [6.6] years; 8121 men [57.8%]). A total of 324 variants were identified that interacted with diet consumption at the suggestive threshold (P < 1 × 10−5). In gene-based analysis, aggregation of multiple EPDR1 gene variants was found to interact with fish intake regarding CRC risk. Furthermore, gene-set enrichment analysis found that several sets of protein-coding genes, which were overrepresented with particular functions and pathways, interacted with the consumption of milk (ART), cheese (OR), tea (KRT), and alcohol (PRM and TNP).

Conclusions and Relevance

In this nested case-control study, the risk of CRC associated with fish intake was modified by multiple single-nucleotide polymorphisms of the EPDR1 gene. The findings further suggested possible functions and pathways that might link the consumption of milk, cheese, tea, and alcohol with CRC development.
The reciprocal relationship between child maltreatment and children's bullying victimization in China
Authors: Xie Ruibo , Wu Wei , Jiang Min , Sun Zhaoxing , Li Weijian , Ding Wan
Published: February 2024

Children who experience physical and psychological maltreatment within their family are more likely to become victims of abuse outside the family. In Chinese culture, children's victimization may also be a precursor to parenting behaviors. Nevertheless, the reciprocal relationship between child maltreatment and children's bullying victimization remains unclear, particularly in Chinese culture. This study aimed to evaluate the reciprocal association between child maltreatment and children's bullying victimization in China, as well as its gender differences. A total of 891 children aged 8–11 years in China participated in the study at four time points. The potential reciprocal link was examined using a cross‐lagged model. The results indicated that physical abuse predicted children's bullying victimization across four time points, while physical neglect predicted children's bullying victimization during the first three time points. The effects of emotional abuse and neglect were negligible. Conversely, children's bullying victimization consistently predicted various types of parental maltreatment over time. Some gender differences in the relationship were found. The findings emphasized a reciprocal relationship between child maltreatment within the family and children's bullying victimization at school. Understanding the cyclical patterns between child maltreatment and bullying victimization may help improve family education approaches and reduce children's bullying victimization.
Latent Tuberculosis Screening Among New Users of a Biologic or Targeted Synthetic Disease‐Modifying Antirheumatic Drug: Gaps in Screening Overall and Among Janus Kinase Inhibitors
Authors: Roberts Eric T. , Schmajuk Gabriela , Li Jing , Murrill Matthew , Yazdany Jinoos
Published: February 2024

Objective

We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease‐modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice.

Methods

Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression.

Results

In the year before drug starts, 65.6% of patients had any TB screening; in a 3‐year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin‐17 inhibitors (IL‐17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year.

Conclusion

We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL‐17i and among Asian and Hispanic patients, as well as low‐performing practices. Educational initiatives, team‐based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed.