Critical review of the impacts of grazing intensity on soil organic carbon storage and other soil quality indicators in extensively managed grasslands.

Livestock grazing intensity (GI) is thought to have a major impact on soil organic carbon (SOC) storage and soil quality indicators in grassland agroecosystems. To critically investigate this, we conducted a global review and meta-analysis of 83 studies of extensive grazing, covering 164 sites across different countries and climatic zones. Unlike previous published reviews we normalized the SOC and total nitrogen (TN) data to a 30 cm depth to be compatible with IPCC guidelines. We also calculated a normalized GI and divided the data into four main groups depending on the regional climate (dry warm, DW; dry cool, DC; moist warm, MW; moist cool, MC). Our results show that taken across all climatic zones and GIs, grazing (below the carrying capacity of the systems) results in a decrease in SOC storage, although its impact on SOC is climate-dependent. When assessed for different regional climates, all GI levels increased SOC stocks under the MW climate (+7.6%) whilst there were reductions under the MC climate (-19%). Under the DW and DC climates, only the low (+5.8%) and low to medium (+16.1%) grazing intensities, respectively, were associated with increased SOC stocks. High GI significantly increased SOC for C4-dominated grassland compared to C3-dominated grassland and C3-C4 mixed grasslands. It was also associated with significant increases in TN and bulk density but had no effect on soil pH. To protect grassland soils from degradation, we recommend that GI and management practices should be optimized according to climate region and grassland type (C3, C4 or C3-C4 mixed).

Interactions between mitochondrial and nuclear DNA in mammalian cells are non-random.

Chromosome Conformation Capture techniques regularly detect physical interactions between mitochondrial and nuclear DNA (i.e. mito-nDNA interactions) in mammalian cells. We have evaluated mito-nDNA interactions captured by HiC and Circular Chromosome Conformation Capture (4C). We show that these mito-nDNA interactions are statistically significant and shared between biological and technical replicates. The most frequent interactions occur with repetitive DNA sequences, including centromeres in human cell lines and the 18S rDNA in mouse cortical astrocytes. Our results demonstrate a degree of selective regulation in the identity of the interacting mitochondrial partners confirming that mito-nDNA interactions in mammalian cells are not random.

The effect of renovation of long-term temperate grassland on N2O emissions and N leaching from contrasting soils.

Renovation of long-term grassland is associated with a peak in soil organic N mineralisation which, coupled with diminished plant N uptake can lead to large gaseous and leaching N losses. This study reports on the effect of ploughing and subsequent N fertilisation on the N2O emissions and DON/NO3(-) leaching, and evaluates the impact of ploughing technique on the magnitude and profile of N losses. This study was carried out on isolated grassland lysimeters of three Irish soils representing contrasting drainage properties (well-drained Clonakilty, moderately-drained Elton and poorly-drained Rathangan). Lysimeters were manually ploughed simulating conventional (CT) and minimum tillage (MT) as two treatments. Renovation of grassland increased N2O flux to a maximum of 0.9kgN2O-Nha(-1) from poorly-drained soil over four days after treatment. Although there was no difference between CT and MT in the post-ploughing period, the treatment influenced subsequent N2O after fertiliser applications. Fertilisation remained the major driver of N losses therefore reducing fertilisation rate post-planting to account for N mineralised through grassland renovation could reduce the losses in medium to longer term. Leaching was a significant loss pathway, with the cumulative drainage volume and N leached highly influenced by soil type. Overall, the total N losses (N2O+N leached) were lowest from poorly and moderately draining soil and highest for the well draining soil, reflecting the dominance of leaching on total N losses and the paramount importance of soil properties.

A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours.

BACKGROUND: Two strategies to interrogate the insulin growth factor 1 receptor (IGF-1R) pathway were investigated: vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation, angiogenesis, and stem cell propagation. METHODS: A phase I, multi-cohort dose escalation study was conducted in patients with advanced solid tumours. Patients received dalotuzumab (10 mg kg(-1)) and escalating doses of MK-2206 (90-200 mg) or escalating doses of dalotuzumab (7.5-10 mg kg(-1)) and MK-0752 (1800 mg) weekly. Upon maximum tolerated dose determination, patients with low-RAS signature, high-IGF1 expression ovarian cancer were randomised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus, whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752. RESULTS: A total of 47 patients were enrolled: 29 in part A (18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm) and 18 in part B (6 in each arm). Dose-limiting toxicities (DLTs) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction, maculopapular rash, and gastrointestinal inflammation. For dalotuzumab/MK-0752, DLTs included grade 3 dehydration, rash, and diarrhoea. Seven patients remained on study for >4 cycles. CONCLUSIONS: Dalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable. Further developments of prospectively validated predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed.

Elastohydrodynamics of the eyelid wiper.

This paper presents an elastohydrodynamic model of the human eyelid wiper. Standard lubrication theory is applied to the fluid layer between the eyelid wiper and ocular surface. The role of the lubrication film is to reduce the shear stresses by preventing solid to solid contact between the eyelid wiper and ocular surface. For the lubrication film to be effective, it is required that the orientation of the eyelid wiper changes between the opening and closing phases of a blink. In order to model this, the hydrodynamic model is coupled with an elastic mattress model for the soft tissue of the eyelid wiper and ocular surface. This leads to a one-dimensional non-linear partial differential equation governing the fluid pressure in the lubrication film. In order to solve the differential equation, a loading condition or constraint equation must be specified. The resulting system is then solved numerically. The model allows predictions of the tear film flux from under the upper eyelid, as well as normal and shear stresses acting on the ocular surface. These factors are important in relation to dry eye syndrome, deformation of the cornea and contact lens design. It is found that the pressure and shear stress under the eyelid act across a length of approximately 0.1 mm which is consistent with clinical observations. It order to achieve a flow of tears from under the upper eyelid during a blink, the model requires that the normal force the eyelid applies to the ocular surface during the closing phase of the blink is significantly higher than during the opening phase of the blink.

The effect of the lipid layer on tear film behaviour.

This paper investigates the effect of surfactants during tear film deposition and subsequent thinning. The surfactants occur naturally on the surface of the tear film in the form of a lipid layer. A lubrication model is developed that describes lipid spreading and film height evolution. It is shown that lipids may play an important role in drawing the tear film up the cornea during the opening phase of the blink. Further, nonuniform distributions of lipids may lead to a rapid thinning of the tear film behind the advancing lipid front (shock). Experiments using a fluorescein dye technique and using a tearscope were undertaken in order to visualise the motion of the lipid layer and any associated shocks immediately after a blink. It is found that the lipid layer continues to spread upwards on the cornea after the opening phase of the blink, in agreement with the model. Using the experimental data, lipid particles were tracked in order to determine the surface velocity and these results are compared to the model predictions.

The potential of ecotoxicoproteomics in environmental monitoring: biomarker profiling in mussel plasma using ProteinChip array technology.

New global technologies, allowing simultaneous analysis of thousands of genes, proteins, and metabolites (so-called "omics" technologies), are being adopted rapidly by industry, academia, and regulatory agencies. This study evaluated the potential of proteomics in ecotoxicological research (i.e., ecotoxicoproteomics). Filter-feeding mussels (Mytilus edulis) were exposed continuously for 3 wk to oil, or oil spiked with alkylphenols and extra polycyclic aromatic hydrocarbons. The influence of chronic exposure on mussel plasma protein expression was investigated utilizing ProteinChip array technology in combination with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS). Results indicated that exposure to spiked oil had a more significant effect on protein expression in mussels than oil alone. In total, 83 mass peaks (intact or modified proteins/peptides) were significantly altered by spiked oil, while 49 were altered by oil. In exposed organisms, the majority of peaks were upregulated compared to controls (i.e., 69% in oil and 71% in spiked oil). Some peaks (32 in total) were affected by both treatments; however, the degree of response was higher in the spiked oil group for 25 of the 32 commonly affected features. Additionally, certain peaks revealed exposure- or gender-specific responses. Multivariate analysis with regression tree-based methods detected protein patterns associated with exposure that correctly classified masked samples with 90-95% accuracy. Similarly, 92% of females and 85% of males were correctly classified (independent of exposure). Results indicate that proteomics have the potential to make a valuable contribution to environmental monitoring and risk assessment.

Dynamics of tear film deposition and draining.

This paper investigates the deposition of the tear film on the cornea of the human eye. The tear film is laid down by the motion of the upper eyelid and then subsequently flows and thins. Of particular interest is the stability of the tear layer and the development of dry patches on the cornea. While there has been significant research on the behaviour of tear films between blinks, this paper focuses on understanding the mechanisms which control the shape and thickness of the deposited film and how this affects the subsequent film behaviour. Numerical and analytical methods are applied to a lubrication model which includes the effects of surface tension, viscosity, gravity and evaporation. The model reveals the importance of the eyelid velocity, motion of the surface lipid layer and the storage of tear film between blinks.

Transepidermal water loss dynamics of human vulvar and thigh skin.

Refinement in procedures to assess skin surface water loss (SSWL) dynamics of the vulvar skin on a large sample of subjects (60) is described and compared to another semi-occluded skin site, the inner thigh. Vulvar SSWL significantly decreased over a 30-min period from 46.2 +/- 2.6 (SE) to 24.7 +/- 1.6 g m(-2) h (p < 0.001). The inner thigh, another semi-occluded region, showed no similar pattern for SSWL (6.2 +/- 0.3 to 6.6 +/- 0.5 g m(-2) h), and the values were significantly less than those for vulvar skin. There was no significant effect of age, body mass index or atopic status on vulvar SSWL.

Temperature-dependent physiological response of Carcinus maenas exposed to copper.

The effect of temperature on the heart rate (fH) of Carcinus maenas exposed to a sublethal nominal concentration (0.5 mg l(-1)) of copper is reported. Adult, intermoult males (4 cm carapace width) were collected from Stavanger Fjord (Norway) in August (seawater TEMPERATURE=17 degrees C) and maintained in the laboratory (fed ad libitum) at 5, 15 and 25 degrees C for 7 days. Following this holding period, crabs were exposed to waterborne copper at the same temperature. After 3 days of exposure, individual fH was measured using the non-invasive Computer Aided Physiological MONitoring system (CAPMON) method. Copper-exposed individuals demonstrated significantly increased fH compared with controls at 5 and 25 degrees C (P<0.01). It is inferred that physiological function in C. maenas may be more vulnerable to copper contamination at seasonal temperature extremes (5 and 25 degrees C) than at the 'standard' test temperature (15 degrees C). Additionally, cardiac arrest observed at 5 degrees C is interpreted as a physiological response to limit copper uptake while the erratic fH in the 25 degrees C group reflected enhanced copper toxicity.

Differential sensitivity of three marine invertebrates to copper assessed using multiple biomarkers.

Understanding how biomarkers relate to each other on exposure to particular contaminants in different species is key to their widespread application in environmental management. However, few studies have systematically used multiple biomarkers in more than a single species to determine the variability of sublethal effects of a particular contaminant. In this study, three marine invertebrates, the shore crab Carcinus maenas, the common limpet Patella vulgata and the blue mussel Mytilus edulis, were exposed over 7 days in the laboratory to environmentally realistic concentrations of the priority pollutant copper. A combination of molecular, cellular and physiological biomarkers was measured in each organism to detect the toxic effects of copper. Biomarkers included lysosomal stability (neutral red retention), neurotoxicity (acetylcholinesterase activity), metabolic impairment (total haemolymph protein), physiological status (heart rate) and induction of protective metallothionein proteins. P. vulgata was the most sensitive to copper with significant effects measured in all biomarkers at concentrations of 6.1 microg Cu l(-1). In C. maenas, cellular and neurotoxic endpoints were affected significantly only at 68.1 microg Cu l(-1). Exposure to copper also induced metallothionein production in crabs. Over a 7-day exposure period, M. edulis was the most tolerant species to copper with significant effects being observed at the cellular level only at 68.1 microg Cu l(-1) . In all three species, cellular and neurotoxic pathways were more sensitive to disruption than physiological processes (protein and heart rate). Results illustrate how a suite of biomarkers applied to different sentinel species can provide a 'diagnosis of stress', whereby, effects at the molecular level can be used to interpret the level of physiological impairment of the organism.

Biomarker responses and PAH uptake in Mya truncata following exposure to oil-contaminated sediment in an Arctic fjord (Svalbard).

Expanding industrial activity (notably oil and gas exploration) in the Arctic requires assessment of the potential impact of chemicals on marine organisms living in seawater at low temperature. The bivalve Mya truncata is common in Svalbard fjord (Norway) where it experiences low temperature throughout the year. To measure the impact of polycyclic aromatic hydrocarbons (PAH) on M. truncata, the responses of three biomarkers [total oxyradical scavenging capacity-assay (TOSC), plasma membrane stability of haemocytes and respiration rates] were investigated from bivalves exposed to sediment contaminated with a PAH mixture (crude oil). After two weeks of exposure to the contaminated sediment, TOSC showed no change. The high TOSC value (4010+/-1339 unit mg(-1) protein) of Mya truncata (control group) is thought to protect biomolecules with a low turnover rate efficiently in a low food availability environment. In the exposed bivalves, the haemocyte cellular membranes were significantly destabilised compared with controls (P<0.05). Respiration rate of control and PAH-exposed individuals (0.055+/-0.020 mg O(2) dw(-1) h(-1)) was similar and relatively low as is typical for polar bivalves, reflecting a strategy to minimise energy expenditure to cope with 9 months of starvation. Bioaccumulation of PAH by M. truncata was also low, due probably to a combination of low metabolic rate and reduced solubility of the oil compounds at low temperature. Data indicated an uptake of mainly low molecular weight compounds (two and three ring molecules). A good correlation of logBAF(lipid) (bioaccumulation factor) and logK(ow) (octanol/water partitioning coefficient) was shown (r(2)=0.87). Tissue sensitivity and/or functional differences (digestive gland vs. haemocytes), PAH uptake route (dietary vs. gills), the low metabolic rate of M. truncata and the low environmental temperature (reducing the bioavailability of PAH) are factors that help explain these findings.

Assessment of the aversive consequences of acute and chronic administration of the melanocortin agonist, MTII.

BACKGROUND: The synthetic melanocortin (MC) agonist, melanotan-II (MTII), reduces food intake and body weight for hours to days after administration. One early report on the effect of MTII suggested that part of its anorexic action may be mediated by aversive consequences. In that experiment, MTII was found to support a mild conditioned taste aversion (CTA). OBJECTIVE: The present experiments replicate and extend those findings in two additional CTA paradigms to further characterize the aversive effects of MTII in rats. METHODS: Experiment 1 simultaneously assessed the ability of MTII to support CTA and reduce food intake, using a small oral infusion of a novel taste as the conditioned stimulus. Experiment 2 assessed the aversive consequences of chronic MTII administration. To accomplish this, we paired implantation of lithium chloride (LiCl)-, MTII- or saline-containing osmotic minipumps with a constantly available novel flavor. After 7 days, rats received a choice test between the minipump-paired flavor and a previously available neutral flavor. RESULTS: Rats with saline minipumps exhibited no preference for either flavor. By contrast, rats in both the LiCl and MTII minipump groups significantly preferred the neutral flavor, indicating the development of a CTA. Additionally, CTA produced by administration of MTII was found to be more resistant to extinction than that produced by LiCl. CONCLUSIONS: The reduction in food intake caused by MTII is accompanied by aversive consequences regardless of route of administration. These results present difficulties for the development of MCs-based therapies for obesity.

A copepod life-cycle test and growth model for interpreting the effects of lindane.

A full life-cycle test was performed to measure the effects of lindane (3.2-3,200 microg l(-1)) on the survival, development and reproduction of the freshwater copepod Bryocamptus zschokkei. This copepod survived at relatively high concentrations of lindane compared with other freshwater crustaceans with a 10 day LC50 of 241 microg l(-1) (95% CL of 141-440). 'Equiproportional development', which assumes that each moult stage represents a specific proportion of the total development time, and is not affected by processes that influence metabolism such as temperature and food quality, was used to determine the mode of action of lindane on development in B. zschokkei. Development to adult was significantly longer at 100 microg l(-1) lindane compared with the controls, however, development remained equiproportional regardless of lindane exposure. Increased development times, therefore, are not due to a direct effect of lindane on the moulting process but are due probably to reduced food intake or increased metabolism through the stress imposed by toxicant exposure. Although the survival data suggest that B. zschokkei is relatively tolerant of lindane exposure, reproduction was affected at low lindane concentrations. At 32 microg l(-1) lindane, significantly fewer eggs and viable offspring were produced per female compared with the solvent control. At very low lindane concentrations (3.2 and 10 microg l(-1)), there was a significant increase in the numbers of offspring produced per female compared with the controls and this is interpreted as a hormesis effect. In conclusion, a full life-cycle test demonstrated B. zschokkei is relatively sensitive to lindane compared with other freshwater crustaceans. Incorporating a copepod growth model (equiproportional development) into the life-cycle test design, provided information on the dominant mode of action of the toxicant.

Total oxyradical scavenging capacity and cell membrane stability of haemocytes of the Arctic scallop, Chlamys islandicus, following benzo(a)pyrene exposure.

Industrial activities, notably oil and gas industries, are expanding in the Arctic. Most of the biomarkers were developed using temperate organisms living at temperatures above 10 degrees C. Little is known about the biomarker responses of organisms living between -1.88 and 5 degrees C. Therefore, assessment of the toxicity of chemicals to cold-water adapted species is required. In this study, the Arctic scallop, Chlamys islandicus, was selected as a key species for bio-monitoring because of wide distribution in Arctic waters and its commercial value. Test animals, stored in seawater at 2 degrees C, were injected with benzo(a)pyrene (diluted in cod liver oil 5 mg ml(-1)) in the adductor muscle every 24 h for four days giving a final dose of 0, 74 and 90.6 mg kg(-1) wet weight for control, low and high dose, respectively. The biomarkers used were total oxyradical scavenging capacity (TOSC) in the digestive gland and cell membrane stability of haemocytes. TOSC values were significantly reduced (ca. 30%) in exposed groups (P < 0.05), indicating a depletion in oxyradical molecular scavengers. The antioxidant defences appeared to be overwhelmed by the reactive oxygen species as the plasma membranes of haemocytes were destabilised (P < 0.05) probably due to lipid peroxidation. These data indicate that reactive oxygen species (ROS) were produced by Arctic scallops via the metabolisation of benzo(a)pyrene at 2 degrees C.

Heart rate, respiration and total oxyradical scavenging capacity of the Arctic spider crab, Hyas araneus, following exposure to polycyclic aromatic compounds via sediment and injection.

Increasing industrial activity in the European Arctic has raised concerns of the potential anthropogenic impact of chemicals on this polar marine ecosystem. For the past 20 years or so, biomarkers have been developed to provide early-warning signals of detrimental impacts of chemicals on the marine ecosystem, however, most biomarker methods have been established for organisms living in temperate rather than polar waters. Little is known about biomarker responses in organisms living within the temperature range of -1.88 to +5 degrees C. In this study, established biomarkers from temperate studies were tested on the Arctic spider crab Hyas araneus to validate their use in polar ecosystems. H. araneus is common in Svalbard fjord (Norway), although it is a temperate water species occurring from northern Spain to Svalbard at depths from 10 to 1200 m. In this paper, the effects of oil were investigated at 2 degrees C via two routes: (i) injection and (ii) contaminated sediment. After 2 weeks of exposure, heart rate, oxygen consumption and total oxyradical scavenging capacity (TOSC) were measured in the same individuals. In both methods of contaminant exposure, heart rate showed a significant increase compared with the control (P < 0.0001, n = 7); mean heart rate values (+/- S.D.) of H. araneus were 49.06 (+/- 13.72), 57.56 (+/- 7.28) and 63.30 (+/- 6.57) beats per minute in control, injected and sediment-treated groups, respectively. Respiration of H. araneus was not affected significantly by either oil treatment (P > 0.05), but two individuals (n = 8) showed a marked increase in oxygen uptake in the sediment-exposed group. The basal oxygen consumption of control H. araneus was lower (0.025 mg O(2) g wet wt.(-1) h(-1)) than reported for H. araneus living in temperate water. Although TOSC of H. araneus was not affected significantly by either exposure treatment (P > 0.05) the mean TOSC value in the sediment-exposed group was lower than the control, indicating some saturation of the oxyradical scavenging system. Results indicate that although low temperature appears to be the main factor reducing the bioavailability of polycyclic-aromatic hydrocarbons, the relatively low metabolic rate of Arctic H. araneus is also implicated in decreased uptake and metabolism of oil compounds into reactive oxygen species (ROS).

Trace metal uptake by the Chinese mitten crab Eriocheir sinensis: the role of osmoregulation.

Changes in salinity affect the bioavailability and consequent uptake of trace metals by euryhaline invertebrates. In many cases, salinity-related effects on metal uptake can be explained by changes in chemical speciation but salinity may also influence uptake indirectly through its action on osmoregulatory mechanisms. Specifically, it can be hypothesised that trace metal uptake may be reduced at salinities approaching the isosmotic point of a species because, at this point, there is reduced activity of ionic exchange pumps. The present study tested this hypothesis using the Chinese mitten crab, Eriocheir sinensis, a hyper-hypoosmoregulator with an isosmotic point around 33 per thousand. Crabs were exposed to radio-labelled cadmium and zinc at 23, 33 and 43 per thousand for 4 days. To eradicate speciation effects, crabs were exposed to the same concentration of the radio-labelled free metal ion (estimated using MineQL computer software) at each salinity. Haemolymph samples were taken daily and radio-labelled metal concentrations were estimated from radioactivity counts and used to provide relative measures of metal uptake. Neither cadmium nor zinc uptake was lowest at the isosmotic point. The uptake of cadmium increased significantly with increase in salinity, while the uptake of zinc showed no significant change with increased salinity. Thus changes in trace metal uptake rates in E. sinensis do not appear to be controlled only by changes in free metal ion concentrations. The different effects of salinity change on the uptake of cadmium and zinc (in the absence of free metal ion change) also indicate that physiological responses to osmotic change alone do not control metal uptake rates for this species.

Comparative responses to water stress in stay-green, rapid- and slow senescing genotypes of the biomass crop, Miscanthus.

• Although hybrids of the perennial rhizomatous grass Miscanthus give high yields under irrigation, their use as a biomass crop in many locations is limited by inadequate water availability. Here, the effects of reduced water availability on growth are reported for three Miscanthus genotypes with differing responses to drought. • In a controlled environment experiment during a drought treatment M. sinensis hybrid (Sin-H6) had no detectable photosynthesis and negligible leaf conductance, whereas M. × giganteus (Gig-3) continued to photosynthesize and transpire but it shed leaf area through senescence. A M. sacchariflorus line (Sac-5) was generally intermediate in its response. Measurements on 3-y-old stands of Gig-3 and Sin-H6 in the field during a short summer drought in August 1999 confirmed the controlled environment observations. • Stay-green characteristics in Sin-H6 appeared to rely on tight control of transpiration through lowered leaf conductance, although the highest leaf ABA concentrations were not found in this genotype. • Stay-green genotypes, such as Sin-H6, are likely to be important for further breeding of Miscanthus because they appear to make the most effective use of available water.

Magnetic resonance imaging of denervation-induced muscle atrophy: effects of clenbuterol in the rat.

We show that magnetic resonance imaging (MRI) can be used to quantify the amount of muscle in the lower legs of adult rats and to noninvasively monitor the onset and progression of denervation-induced atrophy. Muscle cross-sectional areas determined from 2D gradient-echo MR images allow longitudinal quantification of the protective effects of a beta(2)-adrenergic agonist clenbuterol. We also show that the estimation of clenbuterol's efficacy is improved by computation of the muscle volume. Rapid animal throughput and the ability to accurately estimate efficacy make MRI an attractive technology for studying skeletal muscle atrophy and hypertrophy, allowing the evaluation of potential therapies in longitudinal studies.

Effects of a tartar control whitening dentifrice on tooth shade in a population with long-standing natural stain.

Changing and whitening tooth color in people with long-standing tooth stain without excessive hard tissue abrasion may represent one of the more difficult challenges for whitening dentifrices. An eight-week clinical trial was conducted to evaluate change in tooth color by a silica-based, enamel-safe tartar control whitening dentifrice compared to a marketed baking soda dentifrice control. First, a screening exercise was conducted to identify individuals with long-standing extrinsic dental stain. This exercise targeted adults who reported "stained teeth" and coffee/tea drinking or smoking, but who had no recent history of dental prophylaxis. Targeted subjects were examined for stain (Lobene Index) and tooth shade/color (Vita). A total of 291 adults having extrinsic stain and discolored teeth were enrolled in the study. Subjects were randomized to one of the two treatment groups, and all dentifrice use was unsupervised. Tooth color was measured at 4 and 8 weeks from shade values collected from the 8 incisors, and averages were determined from a linear ordering of the shade guide. A total of 278 evaluable subjects completed the 8-week study. Overall, the tartar control whitening dentifrice group experienced an improvement in color, differing statistically from baseline (p < 0.001) and from the marketed control (p < 0.05). Safety profiles for the two dentifrices were generally similar. Among patients with long-standing extrinsic stain, use of the tartar control whitening dentifrice resulted in superior overall tooth shade and reduced maximum or worst color compared to the marketed baking soda dentifrice control.