Mineral Trioxide Aggregate Material Use in Endodontic Treatment: A Review of the Literature

Objective The purpose of this paper was to review the composition, properties, biocompatibility, and the clinical results involving the use of mineral trioxide aggregate (MTA) materials in endodontic treatment. Methods Electronic search of scientific papers from January 1990 to August 2006 was accomplished using PubMed and Scopus search engines (search terms: MTA, GMTA, WMTA, mineral AND trioxide AND aggregate). Results Selected exclusion criteria resulted in 156 citations from the scientific, peer-reviewed dental literature. MTA materials are derived from a Portland cement parent compound and have been demonstrated to be biocompatible endodontic repair materials, with its biocompatible nature strongly suggested by its ability to form hydroxyappatite when exposed to physiologic solutions. With some exceptions, MTA materials provide better microleakage protection than traditional endodontic repair materials using dye, fluid filtration, and bacterial penetration leakage models. In both animal and human studies, MTA materials have been shown to have excellent potential as pulp-capping and pulpotomy medicaments but studies with long-term follow-up are limited. Preliminary studies suggested a favorable MTA material use as apical and furcation restorative materials as well as medicaments for apexogenesis and apexification treatments; however, long-term clinical studies are needed in these areas. Conclusion MTA materials have been shown to have a biocompatible nature and have excellent potential in endodontic use. MTA materials are a refined Portland cement material and the substitution of Portland cement for MTA products is presently discouraged. Existing human studies involving MTA materials are very promising, however, insufficient randomized, double-blind clinical studies of sufficient duration exist involving MTA for all of its clinical indications. Further clinical studies are needed in these areas

Feasibility of multiphoton microscopy-based quantification of antibiotic uptake into neutrophil granulocytes

Antibiotic levels in livestock are usually evaluated through destructive analysis. Taking advantage of the fluorescent properties of marbofloxacin (MBX) and trovafloxacin (TVX), multiphoton microscopy (MPM) was evaluated as a minimally invasive and nondestructive method to determine the penetration of TVX and MBX into sheep neutrophils. Standard curves were measured with drug-only solutions and suggested that MBX was more suited for this type of analysis. The intracellular concentration of both TVX and MBX was higher than the extracellular concentration after incubating neutrophils for 30 min at concentrations ranging from 0.1 to 100 mu g/ml for both the drugs. The intracellular concentration of TVX increased with the extracellular concentration but was always greater than the extracellular concentration, suggesting active internalization. On the other hand, intracellular/extracellular ratio (I/E) peaked at 1.6-fold I/E for 1 mu g/ml and then gradually decreased with increased concentration to 1.2-fold I/E at 100 mu g/ml. For the first time, this study showed the use of MPM to quantify antibiotic uptake by sheep neutrophils and observed that both antibiotics were taken up by sheep neutrophils beyond extracellular levels. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI

Sensitivity of Vertebrate Embryos to Heavy Metals as a Criterion of Water Quality, Phase II: Bioassay Procedures Using Developmental Stages as Test Organisms

Chick, amphibian, and fish embryos were evaluated as bioassay and bioindicator organisms. Test procedures were developed by which embryonic stages may be used 1) in bioassay systems to evaluate the toxicity of particular metallic or metal-containing trace contaminants, and 20 as bioindicators to monitor the quality of natural water resources. A bioassay technique was devised in which metallic toxicants were administered to chick embryos by needle tract injection into the yolk sac. This provided more uniform distribution of test metals throughout the yolk mass than can be obtained by conventional yolk sac injection methods, and gave more sensitivity and uniformity of test results. Metals such as arsenic, cadmium, mercury, lead and zinc are easily detectable at a level of 1 ppb. An in vitroculture technique was developed by which embryos of aquatic vertebrates may be maintained for bioassay and bioindicator purposes. Five test species were identified, suitable synthetic culture water was formulated, and culture monitoring procedures were determined. Most toxic metals (e.g., mercury) may be detected at 1ppb or less with the use of more sensitive embryonic species (e.g., trout). Early cleavage stages of the leopard frog (Rana pipiens) proved more sensitive to cadmium than older embryos, similar to results obtained in Phase I with mercury treatment of frog embryos. Early developmental stages, therefore, have proven especially important for use in bioassay and bioindicator systems

Therapeutic drug monitoring of the β-lactam antibiotics: what is the evidence and which patients should we be using it for?

Traditional antibiotic dosing was not designed for today's escalating antibiotic resistance, lack of novel antibiotics and growing complexity in patient populations. Dosing that ensures optimal antibiotic exposures should be considered essential to increase the likelihood of effective patient treatment. Given the variability in these exposures across different patients, a ‘one-dose-fits-all' approach is increasingly problematic. Therapeutic drug monitoring (TDM) of the β-lactams, the most widely used antibiotic class, is underutilized in certain populations. Clinical experience with β-lactam TDM remains relatively scarce. Patients most likely to benefit from such an intervention include the critically ill, the obese, the elderly and those with cystic fibrosis. Most centres actively performing β-lactam TDM target a minimum 100% of the time during the dosing interval that the free (unbound) concentration of antibiotic exceeds the MIC of the pathogen (100% fT>MIC), which is higher than a traditional target supported by in vitro data. Ideally, isolated pathogens should undergo MIC testing along with TDM on a regular basis, allowing clinicians to address the triad of bug, drug and patient (‘mug') in equal measur

Achieving Specificity in Selected and Wild-Type N Peptide−RNA Complexes: The Importance of Discrimination against Noncognate RNA Targets

The boxB RNA pentaloops from the P22 and λ phages each adopt a GNRA tetraloop fold upon binding their cognate arginine-rich N peptides. The third loop base in P22 boxB (3-out) and the fourth in λ boxB (4-out) are excluded to accommodate this structure. Previously, we selected a pool of λ N sequences with random amino acids at loop contacting positions 13−22 for binding to either of these two GNRA-folded pentaloops or a canonical GNRA tetraloop and isolated a class of peptides with a new conserved arginine (R15). Here, we characterize the binding of λ N and these R15 peptides using fluorescent titrations with 2-aminopurine labeled versions of the three GNRA-folded loops and circular dichroism spectrometry. All peptides preferentially bind the λ boxB RNA loop. λ N and R15 peptide specificity against the P22 loop arises from the cost of rearranging its loop into the 4-out GNRA structure. Modeling indicates that the interaction of R8 with an additional loop phosphate in the 4-out GNRA pentaloop selectively stabilizes this complex relative to the tetraloop. R15 peptides gain additional discrimination against the tetraloop because their arginine also preferentially interacts with the 4-out GNRA pentaloop phosphate backbone, whereas K14 and W18 of λ N contribute equal affinity when binding the tetraloop. Nonspecific electrostatic interactions by basic residues near the C-termini of these peptides create significantly steeper salt dependencies in association constants for noncognate loops, aiding discrimination at high salt concentrations. Our results emphasize the importance of considering specificity against noncognate as well as nonspecific targets in the combinatorial and rational design of biopolymers capable of macromolecular recognition

Achieving Specificity in Selected and Wild-Type N Peptide−RNA Complexes: The Importance of Discrimination against Noncognate RNA Targets

The boxB RNA pentaloops from the P22 and λ phages each adopt a GNRA tetraloop fold upon binding their cognate arginine-rich N peptides. The third loop base in P22 boxB (3-out) and the fourth in λ boxB (4-out) are excluded to accommodate this structure. Previously, we selected a pool of λ N sequences with random amino acids at loop contacting positions 13−22 for binding to either of these two GNRA-folded pentaloops or a canonical GNRA tetraloop and isolated a class of peptides with a new conserved arginine (R15). Here, we characterize the binding of λ N and these R15 peptides using fluorescent titrations with 2-aminopurine labeled versions of the three GNRA-folded loops and circular dichroism spectrometry. All peptides preferentially bind the λ boxB RNA loop. λ N and R15 peptide specificity against the P22 loop arises from the cost of rearranging its loop into the 4-out GNRA structure. Modeling indicates that the interaction of R8 with an additional loop phosphate in the 4-out GNRA pentaloop selectively stabilizes this complex relative to the tetraloop. R15 peptides gain additional discrimination against the tetraloop because their arginine also preferentially interacts with the 4-out GNRA pentaloop phosphate backbone, whereas K14 and W18 of λ N contribute equal affinity when binding the tetraloop. Nonspecific electrostatic interactions by basic residues near the C-termini of these peptides create significantly steeper salt dependencies in association constants for noncognate loops, aiding discrimination at high salt concentrations. Our results emphasize the importance of considering specificity against noncognate as well as nonspecific targets in the combinatorial and rational design of biopolymers capable of macromolecular recognition

Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study

BACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge

Increased police patrols for preventing alcohol-impaired driving.

BACKGROUND: Road traffic injuries cause 1.2 million deaths worldwide each year. Alcohol consumption increases the risk of traffic crashes, especially fatal crashes. Increased police patrols aim to increase both the perceived and actual likelihood of being caught driving while alcohol-impaired, potentially reducing alcohol-related driving, crashes and injuries. OBJECTIVES: To assess the effects on injuries and crashes of increased police patrols that target alcohol-impaired driving. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register (5/2006), CENTRAL (The Cochrane Library 2006, Issue 2), MEDLINE (1966 to 5/2006), TRANSPORT (1968 to 5/2006), C2-SPECTR (2/2005), NCJRS (1/1951 to 5/2006), PsycINFO (1872 to 5/2006), Social Science Citation Index (1974 to 5/2006), SIGLE (1980 to 2/2006), Science Citation Index Expanded (1970 to 5/2006), Dissertation Abstracts (1870 to 5/2006), NTIS (1964 to 12/2004), conference proceedings, and reference lists. We contacted authors of eligible studies. SELECTION CRITERIA: Randomized controlled trials, controlled trials, controlled before and after studies, interrupted time series (ITS) studies, and controlled ITS studies evaluating increased police patrols, either alone or combined with other interventions, targeting alcohol-impaired motor vehicle drivers. DATA COLLECTION AND ANALYSIS: Two investigators independently screened citations, extracted data, and assessed quality criteria. We compared intervention and no-intervention geographical areas or time periods. We re-analyzed study data as required. Results are presented narratively. MAIN RESULTS: The 32 eligible studies included one randomized controlled trial, eight controlled before-after studies, 14 controlled ITS studies, six ITS studies, and three studies with both ITS and controlled before-after analyses. Most interventions targeted only alcohol-impaired driving (69%) and included additional interventions such as media campaigns or special training for police officers (91%). Only two studies reported sufficient information to assess study quality completely. Two-thirds of studies were scored 'not adequate' on at least one feature. Five of six studies evaluating traffic fatalities reported reductions with the intervention, but differences were statistically significant in only one study. Effects of intervention on traffic injuries were inconsistent in the six studies evaluating this outcome, and no results were statistically significant. All four controlled studies evaluating fatal crashes reported reductions with the intervention, which were statistically significant in one study. All 12 controlled studies assessing injury crashes reported greater reductions with the intervention, though effects were minimal or not significant in several studies. ITS studies showed less consistent effects on fatal crashes (three studies) and injury crashes (four studies), and effect estimates were typically imprecise. Thirteen of 20 studies showed reductions in total crashes and about two-thirds of these were statistically significant. AUTHORS' CONCLUSIONS: Studies examining increased police patrol programs were generally consistent in reporting beneficial effects on traffic crashes and fatalities, but study quality and reporting were often poor. Methodological limitations included inadequate sample size, dissimilar baseline measures, contamination, and inadequate data analysis. Thus existing evidence, although supportive, does not firmly establish whether increased police patrols, implemented with or without other intervention elements, reduce the adverse consequences of alcohol-impaired driving

Lack of growth enhancement by exogenous growth hormone treatment in yellow perch (Perca flavescens) in four separate experiments

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Aquaculture 250 (2005): 471-479, doi:10.1016/j.aquaculture.2005.03.019.The effect of exogenous growth hormone (GH) treatment on the growth of juvenile yellow perch (Perca flavescens) was investigated in four experiments. In the first two experiments, juvenile yellow perch were reared at either 13°C or 21°C, and injected weekly with bovine GH (bGH) at 0.1, 1.0 or 10.0 μg/g body weight for 84 days. No significant growth enhancement in GH-treated fish was measured in fish in either of the experiments. In the third experiment, juvenile yellow perch were treated with estradiol-17β (E2, 15 μg/g of diet), bGH (1.0 μg/g body weight) injected weekly or both hormones for 70 days at 21°C. E2 alone stimulated growth, but no further growth stimulation occurred in the E2 + bGH-treated fish. In addition, no growth enhancement was found in fish treated with bGH alone. We measured no difference in serum insulin-like growth factor-I (IGF-I) levels between the treatment groups at 12 and 24 h after the final injection of GH; however, a drop in IGF-I levels after 24 h was observed. In a fourth study, the effect of recombinant yellow perch GH (rypGH, 0.2 or 1.0 μg/g body weight) injected weekly was evaluated in yellow perch juveniles. The fish were reared for 42 days at 18°C. Neither GH dosages improved growth compared to control-injected and non-injected fish. Taken together, the lack of effect of mammalian GH or rypGH in our experiments suggests (1) low binding affinity between these hormones and the GH receptor in yellow perch, (2) that the endogenous GH levels were already at biologically maximal levels or (3) that other endocrine factors are needed in order for GH to promote yellow perch growth. The reduction in IGF-I levels 24 h after handling suggests a negative effect of handling stress on the GH-IGF-I axis in yellow perch.This work was supported by the University of Wisconsin-Madison College of Agricultural and Life Sciences and School of Natural Resources; the Wisconsin Department of Natural Resources; the University of Wisconsin Sea Grant College Program, National Oceanic and Atmospheric Administration, US Department of Commerce; the State of Wisconsin (Federal Grant NA46RG0481, Project No. R/AQ-38); and the USDA NOAA Project R/A-05-99, grant #NA86RG0048 to FG and SR. This study was also funded by the Norwegian Research Council (NFR)