bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative study of the oxide scale thermally grown on titanium alloys by ion beam analysis techniques and scanning electron microscopy
Authors: Gutiérrez A. , Pászti F. , Climent-Font A. , Jiménez J.A. , López M.F.
Published: August 2008

In the present work, the oxide layers developed at elevated temperature on three vanadium-free titanium alloys, of interest as implant biomaterials, were studied by Rutherford backscattering spectroscopy, elastic recoil detection analysis, and scanning electron microscopy. The chemical composition of the alloys investigated, in wt%, was Ti–7Nb–6Al, Ti–13Nb–13Zr, and Ti–15Zr–4Nb. Upon oxidation in air at 750 °C, an oxide scale forms, with a chemical composition, morphology, and thickness that depend on the alloy composition and the oxidation time. After equal exposure time, the Ti–7Nb–6Al alloy exhibited the thinnest oxide layer due to the formation of an Al2O3-rich layer. The oxide scale of the two TiNbZr alloys is mainly composed of Ti oxides, with small amounts of Nb and Zr dissolved. For both TiNbZr alloys, the role of the Nb-content on the mechanism of the oxide formation is discussed.
Thermal conductivity of metallic glassy alloys and its relationship to the glass forming ability and the observed cooling rates
Authors: Louzguine-Luzgin Dmitri V. , Saito Takanobu , Saida Junji , Inoue Akihisa
Published: August 2008

In this work, we study the cooling behavior of several typical bulk glassy alloys on casing and present the relationship between the thermal conductivity of a glassy alloy and the cooling rate upon mold casting. The cooling rates obtained for Ti-, Zr-, Pd-, and Cu-based bulk glass forming alloys are found to scale with the thermal conductivities of the studied glassy alloys.
Ciliary Neurotrophic Factor-Mediated Signaling Regulates Neuronal Versus Glial Differentiation of Retinal Stem Cells/Progenitors by Concentration-Dependent Recruitment of Mitogen-Activated Protein Kinase and Janus Kinase-Signal Transducer and Activator of Transcription Pathways in Conjunction with Notch Signaling
Authors: Bhattacharya Sumitra , Das Ani V. , Mallya Kavita B. , Ahmad Iqbal
Published: August 2008

In the retina, as elsewhere in the central nervous system, neurogenesis precedes gliogenesis; that is, the only glia in the retina, Müller cells, are born when the majority of neurons have already been generated. However, our understanding of how the multipotent retinal stem cells/progenitors choose to differentiate along neuronal and glial lineages is unclear. This information is important in promoting directed differentiation of retinal stem cells/progenitors in an ex vivo or in vivo stem cell approach to treating degenerative retinal diseases. Here, using the neurosphere assay, we demonstrate that ciliary neurotrophic factor (CNTF), acting in a concentration-dependent manner, influences the simultaneous differentiation of retinal stem cells/progenitors into neurons or glia. At low CNTF concentrations differentiation of bipolar cells is promoted, whereas high CNTF concentrations facilitate Müller cell differentiation. The two concentrations of CNTF lead to differential activation of mitogen-activated protein kinase and Janus kinase-signal transducer and activator of transcription (Jak-STAT) pathways, with recruitment of the former and the latter for the differentiation of bipolar and Müller cells, respectively. The concentration-dependent recruitment of two disparate pathways toward neurogenesis and gliogenesis occurs in concert with Notch signaling. Furthermore, we demonstrate that the attenuation of Jak-STAT signaling along with Notch signaling facilitates the differentiation of retinal stem cells/progenitors along the rod photoreceptor lineage in vivo. Our observations posit CNTF-mediated signaling as a molecular switch for neuronal versus glial differentiation of retinal stem cells/progenitors and a molecular target for directed neuronal differentiation of retinal stem cells/progenitors as an approach to addressing degenerative changes in the retina.

Disclosure of potential conflicts of interest is found at the end of this article.
IFATS Collection: Adipose Stromal Cell Differentiation Is Reduced by Endothelial Cell Contact and Paracrine Communication: Role of Canonical Wnt Signaling
Authors: Rajashekhar Gangaraju , Traktuev Dmitry O. , Roell William C. , Johnstone Brian H. , Merfeld-Clauss Stephanie , Van Natta Bruce , Rosen Elliot D. , March Keith L. , Clauss Matthias
Published: August 2008

Adipose stromal cells (ASC) are multipotential mesenchymal progenitor cells that are readily induced to undergo adipogenic differentiation, and we have recently demonstrated them to have functional and phenotypic overlap with pericytes lining microvessels in adipose tissues. In this study we addressed the hypothesis that modulation of ASC fate within this perivascular niche can occur via interaction with endothelial cells (EC), which serve to modulate the adipogenic potential of ASC. To this end, we investigated contact as well as paracrine effects of EC on ASC adipogenesis, in two-dimensional coculture and via conditioned medium and analyzed mutual gene expression changes by real-time reverse transcription polymerase chain reaction (PCR). A significant decrease in adipogenic differentiation was observed in ASC when they were cocultured with EC but not control fibroblasts. This endothelial cell-specific effect was accompanied by increased expression of factors involved in Wnt signaling, most prominently Wnt1, Wnt4, and Wnt10a, which are well-known inhibitors of adipogenesis. Suppression of Wnt1 but not Wnt 10a or scrambled control short interfering RNA in cocultures partially reversed the endothelial cell effect, thus increasing adipogenic differentiation, suggesting a plausible role of Wnt1 ligand in modulation of adipogenesis by the vasculature. Furthermore, addition of recombinant Wnt ligand or the Wnt signaling agonist inhibited adipogenic differentiation of ASC in the absence of EC. In conclusion, these data define the relationship in adipose tissue between ASC and EC in the perivascular niche, in which the latter act to repress adipogenesis, thereby stabilizing vasculature. It is tempting to speculate that abnormal endothelial function may be associated with pathologic derepression of adipogenesis.

Disclosure of potential conflicts of interest is found at the end of this article.
Ex Vivo-Expanded Bone Marrow CD34+ Derived Neutrophils Have Limited Bactericidal Ability
Authors: Dick Emily Patricia , Prince Lynne Rebecca , Sabroe Ian
Published: August 2008

Neutropenia as a consequence of bone marrow failure, severe infections, or intensive chemotherapy is frequently associated with life-threatening sepsis. Ex vivo expansion of CD34+ stem cells has been shown to generate apparently functional neutrophils, and the use of autologous ex vivo-expanded cells can reduce the duration of neutropenia. Nonetheless, the principal antimicrobial capabilities of such cells, and thus their true therapeutic potential, is unknown. Using established protocols, we derived mature neutrophils from normal human adult bone marrow (BM) CD34+ cells and compared them with freshly isolated peripheral blood neutrophils (PBN). Despite functional similarities between ex vivo-differentiated neutrophils (EDN) and PBN in assays of respiratory burst and phagocytosis, EDN showed marked impairment in their ability to kill both Escherichia coli and Streptococcus pneumoniae compared with PBN. We found that EDN were able to detect (through Toll-like receptor 2 [TLR2], TLR4, and CD14 expression), phagocytose, and mount a respiratory burst to microorganisms. EDN, however, were unable to release neutrophil elastase in response to formyl-met-leu-phe and showed a significantly reduced expression of neutrophil elastase, cathepsin G myeloperoxidase, and LL-37/human cathelicidin protein 18 (hCAP18) as determined by Western blotting. Ultrastructural analysis was consistent with a failure of normal granule development in EDN. Neutrophils derived from BM CD34+ cells may therefore provide apparently functional cells as assessed by common methodologies; however, important deficiencies may still limit their therapeutic potential. The results presented here suggest additional key tests that such cells may need to undergo prior to clinical use and highlight the potential challenges of using ex vivo modified stem cells in therapeutic settings.

Disclosure of potential conflicts of interest is found at the end of this article.
Strengthening of reinforced high-strength concrete beam–column joints using advanced reinforcement details
Authors: Ha G.-J. , Cho C.-G.
Published: August 2008

Lack of ductility in high-strength concrete members raises serious concerns for overall structural safety, especially for reinforced concrete beam–column joints. In the current study, experimental research was performed to improve the seismic strength and performance of reinforced high-strength concrete exterior beam–column joints under cyclic load reversals. A new design approach for beam–column joints was introduced using advanced reinforcement details. Specimens of reinforced high-strength concrete beam–column joints were manufactured based on the new design method developed from the concept of a moving beam plastic hinge using anchor-type intermediate bars and advanced details of doubly confined closed stirrups in the beam near the joint, and tested for comparison with specimens designed using the conventional approach. The newly developed design approach minimised damage and considerably improved the structural performance of beam–column joints under cyclic load reversals. The manufactured joints were expected to be effective in improving the weakness induced by the brittleness of high-strength concrete in reinforced high-strength concrete beam–column joints.
Xenograft Versus Extraction Alone for Ridge Preservation After Tooth Removal: A Clinical and Histomorphometric Study
Authors: Barone Antonio , Aldini Nicolò Nicoli , Fini Milena , Giardino Roberto , Calvo Guirado José Luis , Covani Ugo
Published: August 2008

Background: The preservation of bone volume immediately after tooth removal might be necessary to optimize the success of implant placement in terms of esthetics and function. The objectives of this randomized clinical trial were two‐fold: 1) to compare the bone dimensional changes following tooth extraction with extraction plus ridge preservation using corticocancellous porcine bone and a collagen membrane; and 2) to analyze and compare histologic and histomorphometric aspects of the extraction‐alone sites to the grafted sites.

Methods: Forty subjects who required tooth extraction and implant placement were enrolled in this study. Using a computer‐generated randomization list, the subjects were randomly assigned to the control group (EXT; extraction alone) or to the test group (RP; ridge‐preservation procedure with corticocancellous porcine bone and collagen membrane). The following parameters were assessed immediately after extraction and 7 months prior to implant placement: plaque index, gingival index, bleeding on probing, horizontal ridge width, and vertical ridge changes. A bone biopsy was taken from the control and test sites 7 months after the surgical treatment. Histologic and histomorphometric analyses were also performed.

Results: A significantly greater horizontal reabsorption was observed at EXT sites (4.3 ± 0.8 mm) compared to RP sites (2.5 ± 1.2 mm). The ridge height reduction at the buccal side was 3.6 ± 1.5 mm for the extraction‐alone group, whereas it was 0.7 ± 1.4 mm for the ridge‐preservation group. Moreover, the vertical change at the lingual sites was 0.4 mm in the ridge‐preservation group and 3 mm in the extraction‐alone group. Forty biopsies were harvested from the experimental sites (test and control sites). The biopsies harvested from the grafted sites revealed the presence of trabecular bone, which was highly mineralized and well structured. Particles of the grafted material could be identified in all samples. The bone formed in the control sites was also well structured with a minor percentage of mineralized bone. The amount of connective tissue was significantly higher in the extraction‐alone group than in the ridge‐preservation group.

Conclusions: The ridge‐preservation approach using porcine bone in combination with collagen membrane significantly limited the resorption of hard tissue ridge after tooth extraction compared to extraction alone. Furthermore, the histologic analysis showed a significantly higher percentage of trabecular bone and total mineralized tissue in ridge‐preservation sites compared to extraction‐alone sites 7 months after tooth removal.
Comparison of the Use of Different Modes of Mechanical Oral Hygiene in Prevention of Plaque and Gingivitis
Authors: Rosema Nanning A.M. , Timmerman Mark F. , Versteeg Paula A. , van Palenstein Helderman Wim H. , Van der Velden Ubele , Van der Weijden G.A.
Published: August 2008

Background: The objective of this study was to evaluate the effect of an oscillating/rotating/pulsating powered toothbrush on plaque and gingivitis prevention over a 9‐month period.

Methods: The study had an examiner‐masked, randomized, three‐group parallel design. A total of 122 subjects ≥18 years of age in good general health and with at least five teeth per quadrant and no pockets ≥5 mm were included. A 3‐week preexperimental period of extensive oral home care, including rinses, was started to improve gingival health. Professional oral hygiene instruction with a manual brush was provided. At baseline, subjects were assigned to one of three regimens: twice daily brushing with a manual toothbrush, a manual toothbrush and the use of floss, or a powered toothbrush. Subjects were professionally instructed in their regimen and given a prophylaxis. Two weeks later, oral hygiene reinforcement was provided. Gingival bleeding, plaque, staining, and gingival abrasion were assessed during the preexperimental period and at baseline, 10 weeks, and 6 and 9 months.

Results: There was a significant reduction in plaque and gingivitis from the preexperimental period to baseline. At 10 weeks and 6 and 9 months, the level of plaque was statistically significantly lower with the powered toothbrush versus the other two regimens (P ≤0.002). At 10 weeks and 6 months, the level of bleeding in the powered toothbrush group was statistically significantly lower versus manual brushing alone (P ≤0.024).

Conclusions: The powered toothbrush maintained lower plaque levels for 9 months following the 3‐week treatment phase better than the manual toothbrush with or without floss. The powered toothbrush showed significant benefits in preventing gingival bleeding versus manual brushing alone. All regimens were safe for oral tissues.
Injectable Simvastatin in Periodontal Defects and Alveolar Ridges: Pilot Studies
Authors: Morris Melissa S. , Lee Yeonju , Lavin Mark T. , Giannini Peter J. , Schmid Marian J. , Marx David B. , Reinhardt Richard A.
Published: August 2008

Background: Topical injection of simvastatin in methylcellulose gel was shown to stimulate bone growth and inflammation over mouse calvaria and in rat mandible models. The purpose of these pilot studies was to evaluate the potential of locally injected simvastatin in human‐sized periodontal defects.

Methods: Chronic periodontal defects were created bilaterally in seven 1‐year‐old beagle dogs: 3‐walled intrabony defects distal of the mandibular second premolar and mesial of the fourth premolar and Class II furcation defects at the buccal furcation of the mandibular first molars. The edentulous space distal to the mandibular canine was left undisturbed. After 16 weeks of healing, defect sites were treated with scaling and root planing, and mandible sides were randomly selected to receive three weekly injections of 0.5 mg simvastatin in 30 μl methylcellulose gel and contralateral gel alone (n = 3) or 2.0 mg simvastatin/methylcellulose gel and contralateral gel alone (n = 4). Two months following drug application, block sections, including teeth and surrounding tissues, and submandibular lymph nodes were obtained for histomorphometric analysis.

Results: Two trends were noted in this pilot study: buccal edentulous ridge thickness was 29% greater with simvastatin, 0.5 mg, compared to gel alone (P = 0.0845), and the simvastatin groups had bone‐height loss in interproximal intrabony and furcation defects, but the length of new cementum in the interproximal intrabony defects was greater with simvastatin, 0.5 mg (0.35 ± 0.14 mm), compared to gel alone (0.06 ± 0.15 mm; P = 0.069). No new cementum was found in furcations.

Conclusions: Multiple injections of simvastatin are not appropriate for the treatment of intrabony or furcation defects. However, this approach shows potential to augment bone thickness in closed alveolar environments.
Internal Decontamination of Dental Implants: An In Vivo Randomized Microbiologic 6‐Month Trial on the Effects of a Chlorhexidine Gel
Authors: Paolantonio Michele , Perinetti Giuseppe , D'Ercole Simonetta , Graziani Filippo , Catamo Giovanni , Sammartino Gilberto , Piccolomini Raffaele
Published: August 2008

Background: Microbial penetration inside an implant's internal cavity results in a bacterial reservoir that has been associated with an area of inflamed connective tissue facing the fixture–abutment junction. The aim of the present clinical trial was to evaluate the effectiveness of a 1% chlorhexidine gel on the internal bacterial contamination of implants with screw‐retained abutments.

Methods: Thirty subjects (age range: 27.3 to 54.2 years) underwent single implant restoration. Three months after prosthodontic restoration, the modified sulcus bleeding index, modified plaque index, full‐mouth plaque score, and full‐mouth bleeding score were recorded. Microbiologic samples were also collected from the internal part of each fixture. Subjects were then divided into two equal groups: control and test groups (CG and TG, respectively). The CG had the abutment screwed and the crown cemented without any further intervention. Conversely, the TG had the internal part of the fixture filled with a 1% chlorhexidine gel before the abutment placement and screw tightening. Six months later, microbiologic and clinical procedures were repeated in both groups. Total bacterial count and multiplex polymerase chain analysis were performed to detect specific pathogens.

Results: Clinical parameters remained stable throughout the study. From baseline to the 6‐month examination, the total bacterial counts underwent a significant reduction in the TG (P <0.05). Detection of the single pathogen species did not show any significant differences. However, periopathogens were detected more frequently in the CG.

Conclusion: The application of a 1% chlorhexidine gel seemed to be an effective method to reduce bacterial colonization of the implant cavity over a 6‐month period.
Local Peptidergic Innervation of Gingiva in Smoking and Non‐Smoking Periodontitis Patients
Authors: Sakallıoğlu Elif Eser , Lütfioğlu Müge , Sakallıoğlu Umur , Dıraman Emine , Pamuk Ferda , Odyakmaz Selcen
Published: August 2008

Background: The present study aimed to investigate the local peptidergic innervation of diseased and healthy periodontia in smokers and non‐smokers.

Methods: Fifteen smokers and 12 non‐smokers, all with localized chronic periodontitis, participated in the study. Periodontally diseased and healthy tooth sites were selected in smokers (groups 1 and 2, respectively) and non‐smokers (groups 3 and 4, respectively). Local peptidergic innervation was assessed by the concentrations of two neuropeptides, substance P (SP) and calcitonin gene‐related peptide (CGRP), in the gingival biopsies obtained from the groups. Clinical data and biopsies were collected from the same two tooth sites in each group. SP and CGRP levels were measured by enzyme immunosorbent assay in the supernatants of gingival samples.

Results: Increased probing depth and attachment loss were found in group 1 compared to group 3 (P <0.05). SP was higher in group 1 compared to groups 2, 3, and 4, and it was higher in group 3 compared to groups 2 and 4 (P <0.05). CGRP was higher in group 1 than in groups 2, 3, and 4, but it was lower in group 3 than in groups 2 and 4 (P <0.05).

Conclusion: The study results suggested that 1) although smoking may affect the neurogenic inflammation in the presence of periodontitis by increasing local peptidergic innervation, this effect may not be seen in periodontal health, and 2) SP may be regarded as an indicator of periodontitis, whereas CGRP may be important in the acute and/or initial periodontal inflammation.
Localized Intermittent Delivery of Simvastatin Hydroxyacid Stimulates Bone Formation in Rats
Authors: Jeon Ju Hyeong , Piepgrass Ward T. , Lin Yi‐Ling , Thomas Mark V. , Puleo David A.
Published: August 2008

Background: The cholesterol‐lowering drug simvastatin promotes bone formation in cell cultures and animal models. In previous studies, devices for the controlled, localized delivery of simvastatin hydroxyacid enhanced osteoblastic activity in vitro. The objective of this investigation was to determine bioactivity of the delivery system in vivo.

Methods: Devices for sustained or intermittent release of simvastatin hydroxyacid were formed using a blend of cellulose acetate phthalate and a poly(ethylene oxide) and poly(propylene oxide) block copolymer, and they were implanted directly over the calvarium of young male rats. Drug‐free devices were used as controls. After 9, 18, or 28 days, specimens were histologically evaluated for new bone formation.

Results: All three groups showed some level of new bone formation, but the extent of osteogenesis depended on the type of implant. Devices delivering simvastatin hydroxyacid were associated with a 77.5% to 133% increase in new woven bone thickness compared to control devices without a drug (P <0.05). Furthermore, intermittent release stimulated a 32.3% greater response in bone thickness and a 74.1% greater bone area than did sustained delivery (P <0.05). Although a minimal thickness of woven bone was formed directly under the device (up to 36 μm), a significantly thicker layer was observed at the periphery (up to 205 μm), implying mechanical and/or chemical effects directly under the implant. The percentage of lamellar bone area for intermittent and sustained release was higher than that for the control group (P <0.05).

Conclusion: Based on the present results of enhanced bone formation, these devices for the intermittent delivery of simvastatin hydroxyacid merit further attention for localized osteogenesis.
The Inflammatory Response in Alzheimer's Disease
Authors: Rogers Joseph
Published: August 2008

Over the last 2 decades, numerous innate inflammatory mediators have been reported to be upregulated in pathologically vulnerable regions of the brain in Alzheimer's disease (AD). These data have led to a reexamination of the dogma of brain immunologic privilege and to new studies that examine the role of the innate inflammatory response in a number of other neurologic disorders, particularly Parkinson's disease and human immunodeficiency virus dementia. In addition, basic science discoveries about neuroinflammation are now beginning to move to the clinic. More than 20 epidemiologic surveys have consistently demonstrated that common non‐steroidal anti‐inflammatory drugs may protect against the development of AD. By contrast, anti‐inflammatory treatment trials for existing AD have typically shown little to no effect on halting or reversing the disorder, although the agents tested have often been at odds with those suggested by the epidemiologic and basic science results. The extensive literature on innate inflammation and neurologic disease notwithstanding, three fundamental questions still remain to be answered fully. First, are innate inflammatory responses a cause of neurologic disease or merely a more sophisticated means than previously imagined for removing the detritus left by more primary pathogenic mechanisms? Second, can anti‐inflammatory agents effectively treat existing neurologic disease, or is a protective strategy in high‐risk patients the only reasonable option? Third, whether for protection or treatment, what is the best choice of anti‐inflammatory agent given the basic science mechanisms and epidemiologic results that have been reported?
The Management of Inflammation in Periodontal Disease
Authors: Van Dyke Thomas E.
Published: August 2008

It has become clear in recent years that periodontitis is an inflammatory disease initiated by oral microbial biofilm. This distinction implies that it is the host response to the biofilm that destroys the periodontium in the pathogenesis of the disease. As our understanding of pathways of inflammation has matured, a better understanding of the molecular basis of resolution of inflammation has emerged. Resolution of inflammation is an active, agonist‐mediated, well‐orchestrated return of tissue homeostasis. There is an important distinction between anti‐inflammation and resolution; anti‐inflammation is pharmacologic intervention in inflammatory pathways, whereas resolution is biologic pathways restoring homeostasis. A growing body of research suggests that chronic inflammatory periodontal disease involves a failure of resolution pathways to restore homeostasis. This article reviews the resolution of inflammation in the context of periodontal disease and the potential for the modification of resolution pathways for the prevention and treatment of periodontal diseases. Proof‐of‐concept studies in the 1980s demonstrated that pharmacologic anti‐inflammation prevented and slowed the progression of periodontal diseases in animals and man. However, the side‐effect profile of such therapies precluded the use of non‐steroidal anti‐inflammatory drugs or other enzyme inhibitors or receptor antagonists in periodontal therapy. The isolation and characterization of resolving agonist molecules has opened a new area of research using endogenous lipid mediators of resolution as potential therapeutic agents for the management of inflammatory periodontitis. Work in animal models of periodontitis has revealed the potential of this therapeutic approach for its prevention and treatment and forced the reconsideration of our understanding of the pathogenesis of human periodontal diseases.
Host‐Response Therapeutics for Periodontal Diseases
Authors: Giannobile William V.
Published: August 2008

Periodontal diseases are initiated by Gram‐negative tooth‐associated microbial biofilms that elicit a host response, with resultant osseous and soft tissue destruction. In response to endotoxins derived from periodontal pathogens, several osteoclast‐related mediators target the destruction of alveolar bone and supporting connective tissues. Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins, and other osteoclast‐derived enzymes. This article focuses on the downstream factors of the osteoclast responsible for the degradation of bone and soft tissues around teeth and oral implants. Furthermore, therapeutic approaches that target MMP‐2, −8, and −9 inhibition, such as MMP inhibitors, chemically modified tetracyclines, and subantimicrobial formulations of tetracycline analogues, are discussed. The use of rapid, chair‐side tests of MMP activity, in particular for MMP‐8 and bone collagen fragments, show strong potential as non‐invasive measures of tissue health or disease. In addition, studies using other agents for the preservation of bone mass, such as bisphosphonates that inhibit osteoclast recruitment, are highlighted. The application of these bone‐preservation strategies to periodontal management and treatment are discussed in the context of high‐risk patients susceptible to disease reactivation or disease complications.
Hydro-economic analysis of water supply for the binational transboundary region of Baja California, Mexico
Authors: Medellín-Azuara J. , Mendoza-Espinosa L. G. , Lund J. R. , Howitt R. E.
Published: August 2008

The northern border of Baja California hosts prominent agriculture and fast-growing cities under an extreme-arid climate. This paper provides an economic-engineering analysis of water supply alternatives to cope with agricultural, environmental and urban water needs projected to year 2025. Analysed alternatives include idealised water markets, wastewater reuse, seawater desalination and infrastructural expansions. Network flow optimisation using CALVIN (CALifornia Value Integrated Network) was employed. A database of the water system was built to include hydrology; agricultural, environmental and urban demands infrastructure, and economic information on operating costs and economic value of water. For the coastal cities, results show that wastewater reuse along with other already projected infrastructure expansions is overall the most economically promising alternative. Water markets offer leverage and flexibility for future urban needs. However, some locations cannot take advantage of domestic water markets with current aqueduct capacities. Worthwhile investments in infrastructure include an expanded aqueduct connecting coast and inland water supply systems. Furthermore, at current urban water prices and operating costs, seawater desalination is uneconomical for Baja California. Computer models are useful to better understand water-related issues in a region and provide a technical basis for developing and comparing long-term water management solutions.
Type of Archwire and Level of Acidity: Effects on the Release of Metal Ions from Orthodontic Appliances
Authors: Kuhta Maja , Pavlin Dubravko , Slaj Martina , Varga Suzana , Lapter-Varga Marina , Slaj Mladen
Published: August 2008

Objective: To examine the effects of three different parameters—pH value, type of archwire, and length of immersion—on release of metal ions from orthodontic appliances.

Materials and Methods: Simulated fixed orthodontic appliances that corresponded to one-half of the maxillary arch were immersed in artificial saliva of different pH values (6.75 ± 0.15 and 3.5 ± 0.15) during a 28-day period. Three types of archwires were used: stainless steel (SS), nickel-titanium (NiTi), and thermo NiTi. The quantity of metal ions was determined with the use of a high-resolution mass spectrophotometer (HR-ICP/MS).

Results: The release of six different metal ions was observed: titanium (Ti), chromium (Cr), nickel (Ni), iron (Fe), copper (Cu), and zinc (Zn). Repeated measures statistical analysis of variance (ANOVA) was used. Results showed that (1) the appliances released measurable quantities of all ions examined; (2) the change in pH had a very strong effect (up to 100-fold) on the release of ions; and (3) the release of ions was dependent on wire composition, but it was not proportional to the content of metal in the wire. The largest number of ions was released during the first week of appliance immersion.

Conclusion: Levels of released ions are sufficient to cause delayed allergic reactions. This must be taken into account when type of archwire is selected, especially in patients with hypersensitivity or compromised oral hygiene.
Microleakage under Ceramic and Metallic Brackets Bonded with Resin-Modified Glass Ionomer
Authors: Ramoglu Sabri Ilhan , Uysal Tancan , Ulker Mustafa , Ertas Huseyin
Published: August 2008

Objective: To test the null hypothesis that there is no significant difference between the microleakage of adhesive interferences at the occlusal and gingival margins of both ceramic and metallic brackets bonded with light-cured resin-modified glass ionomer and a conventional adhesive.

Materials and Methods: Sixty freshly extracted human maxillary premolar teeth were randomly divided into four groups of 15 teeth each. Metal and ceramic brackets were bonded to groups 1 and 2 with resin-modified glass ionomer adhesive (RMGIA). Metal and ceramic brackets were bonded to group 3 and group 4 with a conventional adhesive (CA) system. A dye-penetration method was used for microleakage evaluation. Microleakage from the occlusal and gingival margins was determined by a stereomicroscope for the enamel-adhesive and bracket-adhesive interfaces. Statistical analysis was performed using the Kruskal-Wallis test and the Mann-Whitney U-test with a Bonferroni correction.

Results: The gingival side of all groups exhibited higher microleakage scores compared with the occlusal side for both adhesive interfaces. All bracket and adhesive combinations displayed statistically significant differences in microleakage between the enamel-adhesive and adhesive-bracket interfaces at the occlusal and gingival sides of the brackets (P < .001). When the adhesive systems were compared, the RMGIA showed more microleakage than the CA between the different interfaces.

Conclusions: The hypothesis is rejected. RMGIA results in more microleakage between enamel-adhesive interfaces.
A Severe Reaction to Ni-Containing Orthodontic Appliances
Authors: Kolokitha Olga Elpis , Chatzistavrou Evangelia
Published: August 2008

Exposure to nickel-containing orthodontic appliances may cause intra- or extraoral allergic reactions. Nickel is the most typical antigen implicated in causing allergic contact dermatitis, which is a Type IV delayed hypersensitivity immune response. This report presents an unusual reaction to nickel during the orthodontic treatment of an adult female patient. The patient had no previous history of allergy and had been wearing fixed metal upper appliances while in orthodontic treatment to assist the eruption of her impacted teeth. The adverse hypersensitivity reactions appeared only after the surgical exposure and included severe signs of eczematic and urticarial reactions of the face with redness, irritation, itching, eczema, soreness, fissuring, and desquamation as well as intraoral diffuse red zones. Diagnostic patch testing performed by the allergist revealed sensitization to nickel (++++ score). Treatment was achieved with nickel-free appliances.
Type 1 Diabetic Akita Mouse Hearts Are Insulin Sensitive but Manifest Structurally Abnormal Mitochondria That Remain Coupled Despite Increased Uncoupling Protein 3
Authors: Bugger Heiko , Boudina Sihem , Hu Xiao Xuan , Tuinei Joseph , Zaha Vlad G. , Theobald Heather A. , Yun Ui Jeong , McQueen Alfred P. , Wayment Benjamin , Litwin Sheldon E. , Abel E. Dale
Published: August 2008

OBJECTIVE— Fatty acid–induced mitochondrial uncoupling and oxidative stress have been proposed to reduce cardiac efficiency and contribute to cardiac dysfunction in type 2 diabetes. We hypothesized that mitochondrial uncoupling may also contribute to reduced cardiac efficiency and contractile dysfunction in the type 1 diabetic Akita mouse model (Akita).

RESEARCH DESIGN AND METHODS— Cardiac function and substrate utilization were determined in isolated working hearts and in vivo function by echocardiography. Mitochondrial function and coupling were determined in saponin-permeabilized fibers, and proton leak kinetics was determined in isolated mitochondria. Hydrogen peroxide production and aconitase activity were measured in isolated mitochondria, and total reactive oxygen species (ROS) were measured in heart homogenates.

RESULTS— Resting cardiac function was normal in Akita mice, and myocardial insulin sensitivity was preserved. Although Akita hearts oxidized more fatty acids, myocardial O2 consumption was not increased, and cardiac efficiency was not reduced. ADP-stimulated mitochondrial oxygen consumption and ATP synthesis were decreased, and mitochondria showed grossly abnormal morphology in Akita. There was no evidence of oxidative stress, and despite a twofold increase in uncoupling protein 3 (UCP3) content, ATP-to-O ratios and proton leak kinetics were unchanged, even after perfusion of Akita hearts with 1 mmol/l palmitate.

CONCLUSIONS— Insulin-deficient Akita hearts do not exhibit fatty acid–induced mitochondrial uncoupling, indicating important differences in the basis for mitochondrial dysfunction between insulin-responsive type 1 versus insulin-resistant type 2 diabetic hearts. Increased UCP3 levels do not automatically increase mitochondrial uncoupling in the heart, which supports the hypothesis that fatty acid–induced mitochondrial uncoupling as exists in type 2 diabetic hearts requires a concomitant increase in ROS generation.
An index of myocardial performance applied to the right ventricle of Boxers with arrhythmogenic right ventricular cardiomyopathy
Authors: Baumwart Ryan D. , Meurs Kathryn M.
Published: August 2008

Objective—To use an index of myocardial performance (IMP) to assess right ventricular function in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC).

Animals—22 Boxers (12 Boxers with ARVC diagnosed by the detection of ≥ 1,000 ventricular premature complexes (VPCs)/24 h and 10 Boxers with ≤ 5 VPCs/24 h (control dogs).

Procedures—Pulsed-wave Doppler recordings of tricuspid inflow and pulmonic outflow were acquired. Preejection period (PEP), ejection time (ET), PEP/ET, and IMP were determined for the right ventricle by use of data from separate cardiac cycles.

Results—A significant difference was not identified between groups for right ventricular PEP, right ventricular ET, right ventricular PEP/ET, or right ventricular IMP. Right ventricular IMP was not significantly correlated with VPC number (r = 0.21) or VPC grade (r = −0.3) in Boxers with ARVC.

Conclusions and Clinical Relevance—Boxers with ARVC did not have significant differences in right ventricular IMP, compared with results for control Boxers. This would suggest that right ventricular dysfunction does not develop in Boxers with ARVC or that a more severe phenotype of the disease may be necessary for detection of dysfunction. Additional studies that use more sensitive techniques to evaluate myocardial function may be warranted.
Estimation of left ventricular filling pressure by use of Doppler echocardiography in healthy anesthetized dogs subjected to acute volume loading
Authors: Schober Karsten E. , Bonagura John D. , Scansen Brian A. , Stern Joshua A. , Ponzio Nicole M.
Published: August 2008

Objective—To identify Doppler echocardiographic (DE) variables that correlate with left ventricular filling pressure (LVFP).

Animals—7 healthy dogs (1 to 3 years old).

Procedures—Dogs were anesthetized and instrumented to measure left atrial pressure (LAP), left ventricular pressures, and cardiac output. Nine DE variables of LVFP derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler images were measured over a range of hemodynamic states induced by volume loading and right atrial pacing. Associations between simultaneous invasive measures of LVFP and DE measures of LVFP were determined by use of regression analysis. Receiver operating characteristic analysis was used to predict increases in mean LAP on the basis of DE variables.

Results—Mean LAP was correlated with several DE variables: the ratio between peak velocity during early diastolic transmitral flow and left ventricular isovolumic relaxation time (peak E:IVRT) during sinus rhythm and during right atrial pacing, IVRT, the ratio between late diastolic transmitral flow velocity and pulmonary venous flow duration, and the interval between onset of early diastolic mitral annulus motion and onset of early diastolic transmitral flow. Cutoff values of 2.20 and 2.17, for peak E:IVRT in dogs with sinus rhythm and atrial pacing predicted increases in mean LAP (≥ 15 mm Hg) with sensitivities of 90% and 100% and specificities of 92% and 100%, respectively.

Conclusions and Clinical Relevance—Doppler echocardiography can be used to predict an increase in LVFP in healthy anesthetized dogs subjected to volume loading.
Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy
Authors: Meurs Kathryn M. , Hendrix Kristina P. , Norgard Michelle M.
Published: August 2008

Objective—To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation.

Animals—5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs).

Procedures—Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the β-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure.

Results—A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, β-myosin heavy chain, and troponin T genes.

Conclusions and Clinical Relevance—Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.
Cardiac output determination by use of lithium dilution during exercise in horses
Authors: Durando Mary M. , Corley Kevin T. T. , Boston Raymond C. , Birks Eric K.
Published: August 2008

Objective—To compare cardiac output (CO) obtained by the lithium dilution method (LiDCO) with CO calculated from the Fick principle (FickCO), in horses maximally exercising on a high-speed treadmill.

Animals—13 Thoroughbreds.

Procedures—In part 1 of the study, 5 horses performed a warm-up (walk, trot, and canter) and exercise test (walk, trot, canter, and gallop [90% to 100% maximum oxygen consumption [{O2max}]) with measurements of LiDCO and FickCO obtained simultaneously after 60 seconds at each exercise level, for a total of 7 measurements. In part 2 of the study, 8 horses performed a warm-up (walk, trot, and canter) followed by an exercise test (walk and gallop [90% to 100% O2max], repeated twice). Measurements of LiDCO and FickCO were obtained 60 seconds into the first walk and each gallop of the exercise tests, for a total of 3 measurements.

Results—Cardiac output increased significantly with increasing speeds by use of both methods. In part 1, lithium dilution significantly overestimated CO, compared with the Fick principle, during the exercise test (as both injection number and exercise intensity increased). Mean ± SD bias was 246 ± 264 mL of blood/min/kg in part 1 and 67 ± 100mLof blood/kg/min in part 2. Three injections of lithium (part 2) did not result in the same degree of overestimation of LiDCO that was observed with 7 injections (part 1).

Conclusions and Clinical Relevance—Lithium dilution may be an acceptable substitute for the Fick principle as a means to measure CO in maximally exercising client-owned horses.
Evaluation of the mammalian target of rapamycin pathway and the effect of rapamycin on target expression and cellular proliferation in osteosarcoma cells from dogs
Authors: Gordon Ira K. , Ye Fang , Kent Michael S.
Published: August 2008

Objective—To investigate activation of the mammalian target of rapamycin (mTOR) pathway and the antitumor effect of rapamycin in canine osteosarcoma cells.

Sample Population—3 established primary canine osteosarcoma cell lines generated from naturally developing tumors.

Procedures—Expression of total and phosphorylated mTOR and p70S6 kinase was assessed by use of western blot analysis in canine osteosarcoma cells with and without the addition of rapamycin. A clonogenic assay was performed to determine the surviving fraction of osteosarcoma cells at various concentrations of rapamycin.

Results—Total and phosphorylated mTOR and p70S6 kinase expression was evident in all 3 cell lines evaluated, which was indicative of activation of this pathway. Treatment with rapamycin resulted in a time-dependent decrease in phosphorylated mTOR expression and a lack of detectable phosphorylated p70S6 kinase. No detectable change in expression of total mTOR and total p70S6 kinase was identified after rapamycin treatment. The clonogenic assay revealed a significant dose-dependent decrease in the surviving fraction for all 3 cell lines when treated with rapamycin.

Conclusions and Clinical Relevance—These data indicated that mTOR and its downstream product are present and active in canine osteosarcoma cells. The pathway can be inhibited by rapamycin, and treatment of cells with rapamycin decreased the surviving tumor cell fraction. These data support the molecular basis for further investigation into the use of mTOR inhibitors as an antineoplastic approach for dogs with osteosarcoma.
Pharmacokinetics after administration of an injectable experimental long-acting parenteral formulation of doxycycline hyclate in goats
Authors: Vargas Dinorah , Gutierrez Lilia , Juárez Ivan , Gonzalez Francisco , Sumano Héctor
Published: August 2008

Objective—To determine the pharmacokinetics after SC administration of an experimental, long-acting parenteral formulation of doxycycline hyclate in a poloxamer-based matrix and after IV and IM administration of an aqueous formulation of doxycycline hyclate in goats.

Animals—30 clinically normal adult goats.

Procedures—Goats were allocated to 3 groups (10 goats/group). One group of goats received doxycycline hyclate (10 mg/kg) IM, a second group received the same dosage of doxycycline hyclate IV, and the third group received the long-acting parenteral formulation of doxycycline hyclate SC. Serum concentrations of doxycycline were determined before and at various intervals after administration.

Results—The long-acting parenteral formulation of doxycycline hyclate had the greatest bioavailability (545%); mean ± SD maximum serum concentration was 2.4 ± 0.95 μg/mL, peak time to maximum concentration was 19.23 ± 2.03 hours, and elimination half-life was 40.92 ± 4.25 hours.

Conclusions and Clinical Relevance—Results indicated that the long-acting parenteral formulation of doxycycline hyclate distributed quickly and widely throughout the body after a single dose administered SC, and there was a prolonged half-life. Bioavailability of the longacting parenteral formulation of doxycycline hyclate after SC administration was excellent, compared with bioavailability after IV and IM administration of an aqueous formulation of doxycycline hyclate. Although no local tissue irritation and adverse effects were detected, clinical assessment of drug-residues and toxicologic evaluations are warranted before this long-acting parenteral formulation of doxycycline hyclate can be considered for use in goats with bacterial infections.