On the use of Europium (Eu) for designing new metal-based anticancer drugs.

Europium oxide (Eu2O3) was used to evaluate the affinity of this rare earth element for interacting with double-stranded (ds) DNA molecules. To perform the study, we used single molecule force spectroscopy with optical tweezers and gel electrophoresis assays. Force spectroscopy experiments show that Eu2O3 presents a strong interaction with dsDNA, and the binding is independent on the ionic strength used in the surrounding environment. Among the main characteristics of the interaction, Eu2O3 tends to bind in a cooperative way, forming bound clusters of ∼ 3 molecules, and presents a high equilibrium association binding constant on the order of 105 M-1. In addition, gel electrophoresis confirm the weak electrostatic character of the interaction and explicit show that Eu2O3 does not interfere on drug intercalation into the double-helix. Such results demonstrate the potential of europium for interacting with nucleic acids and strongly suggest that this rare earth element may be considered for the design of new metal-based anticancer drugs in the future.

Immunological effects of altering the concentrate inclusion level in a grass silage-based diet for early lactation Holstein Friesian cows.

Concentrate inclusion levels in dairy cow diets are often adjusted so that the milk yield responses remain economic. While changes in concentrate level on performance is well known, their impact on other biological parameters, including immune function, is less well understood. The objective of this study was to evaluate the effect of concentrate inclusion level in a grass silage-based mixed ration on immune function. Following calving 63 (45 multiparous and 18 primiparous) Holstein Friesian dairy cows were allocated to one of three isonitrogenous diets for the first 70 days of lactation. Diets comprised of a mixture of concentrates and grass silage, with concentrates comprising either a low (30%, LC), medium (50%, MC) or high (70%, HC) proportion of the diet on a dry matter (DM) basis. Daily DM intakes, milk yields and BW were recorded, along with weekly body condition score, milk composition and vaginal mucus scores. Blood biochemistry was measured using a chemistry analyzer, neutrophil phagocytic and oxidative burst assessed using commercial kits and flow cytometry, and interferon-γ production evaluated by ELISA after whole blood stimulation. Over the study period cows on HC had a higher total DM intake, milk yield, fat yield, protein yield, fat+protein yield, protein content, mean BW and mean daily energy balance, and a lower BW loss than cows on MC, whose respective values were higher than cows on LC. Cows on HC and MC had a lower serum non-esterified fatty acid concentration than cows on LC (0.37, 0.37 and 0.50 mmol/l, respectively, P=0.005, SED=0.032), while cows on HC had a lower serum ß-hydroxybutyrate concentration than cows on MC and LC (0.42, 0.55 and 0.55 mmol/l, respectively, P=0.002, SED=0.03). Concentrate inclusion level had no effect on vaginal mucus scores. At week 3 postpartum, cows on HC tended to have a higher percentage of oxidative burst positive neutrophils than cows on LC (43.2% and 35.3%, respectively, P=0.078, SED=3.11), although at all other times concentrate inclusion level in the total mixed ration had no effect on neutrophil phagocytic or oxidative burst characteristics, or on interferon-γ production by pokeweed mitogen stimulated whole blood culture. This study demonstrates that for high yielding Holstein Friesian cows managed on a grass silage-based diet, concentrate inclusion levels in early lactation affects performance but has no effect on neutrophil or lymphocyte immune parameters.

Does the diurnal pattern of enteric methane emissions from dairy cows change over time?

Diet manipulation and genetic selection are two important mitigation strategies for reducing enteric methane (CH4) emissions from ruminant livestock. The aim of this study was to assess whether the diurnal pattern of CH4 emissions from individual dairy cows changes over time when cows are fed on diets varying in forage composition. Emissions of CH4 from 36 cows were measured during milking in an automatic (robotic) milking station in three consecutive feeding periods, for a total of 84 days. In Periods 1 and 2, the 36 cows were fed a high-forage partial mixed ration (PMR) containing 75% forage, with either a high grass silage or high maize silage content. In Period 3, cows were fed a commercial PMR containing 69% forage. Cows were offered PMR ad libitum plus concentrates during milking and CH4 emitted by individual cows was sampled during 8662 milkings. A linear mixed model was used to assess differences among cows, feeding periods and time of day. Considerable variation was observed among cows in daily mean and diurnal patterns of CH4 emissions. On average, cows produced less CH4 when fed on the commercial PMR in feeding Period 3 than when the same cows were fed on high-forage diets in feeding Periods 1 and 2. The average diurnal pattern for CH4 emissions did not significantly change between feeding periods and as lactation progressed. Emissions of CH4 were positively associated with dry matter (DM) intake and forage DM intake. It is concluded that if the management of feed allocation remains constant then the diurnal pattern of CH4 emissions from dairy cows will not necessarily alter over time. A change in diet composition may bring about an increase or decrease in absolute emissions over a 24-h period without significantly changing the diurnal pattern unless management of feed allocation changes. These findings are important for CH4 monitoring techniques that involve taking measurements over short periods within a day rather than complete 24-h observations.

Femoral neck fractures in osteogenesis imperfecta treated with bisphosphonates.

PURPOSE: Osteogenesis imperfecta (OI) is a condition characterised by bone fragility and multiple fractures, which cause considerable morbidity in the affected patients. Most cases are associated with mutations in one of the type I collagen genes. Recently, bisphosponates have been used widely to reduce pain and the incidence of fragility fractures in OI in children, even though there have been concerns raised regarding the long-term complications of it due to their effect on the bone. The fragility fractures involving the neck of the femur in children with intramedullary rods in the femoral shaft are very difficult to treat. Although these fractures are frequently un-displaced, they require optimal internal fixation to achieve fracture union. The aim of this study was to assess the clinical and radiological outcomes of OI patients with intracapsular femoral neck fracture treated with headless compression screws. METHOD AND RESULTS: At our institute, we identified seven patients (11 hips) with OI who underwent internal fixation with headless compression screws for a neck of femur fracture between June 2010 and Dec 2012. The time to fractures healing was on average 14 weeks (12 to 16). All patients gained their pre-injury ambulatory status. CONCLUSION: It is very challenging and technically demanding for orthopaedic surgeons when treating the fragility fracture of the neck of femur in patients with intramedullary rod in the femoral shaft. The published data regarding the management of these complex conditions are very limited. We describe our experience with the technique of percutaneous headless compression screw fixation for treating the femoral neck fractures in OI patients.

Limb reconstruction in Ollier's disease.

We present our experience of lengthening and correction of complex deformities in the management of patients with Ollier's dysplasia (multiple enchondromatosis) from 1985 and 2002. All patients were under 18 years with a minimum follow-up time of 2 years (mean 9.6 years, range 2-15 years). There were a total of ten patients of which seven were male and three female. The mean age at presentation was 10.7 years (range 5-17 years; SD 3.7 years). The total length gain was 42.3 mm (range 30-110 mm; SD 28.9 mm). The number of days in external fixation was 164.8 days (range 76-244 days; SD 42.9 days). The bone healing index was 32.5 days/cm (18-50 days/cm; SD 10.3 days/cm). Patients with Ollier's disease have limb length inequality and angular deformities and require multiple reconstructive procedures owing to a high incidence of recurrence. We identified a tendency for the osteotomy to prematurely consolidate and advise the latency period after surgery to be 4-5 days and for distraction to proceed at a faster rate.

Nitrous oxide emissions from cattle excreta applied to a Scottish grassland: effects of soil and climatic conditions and a nitrification inhibitor.

Dung and urine excreted onto grasslands are a major source of nitrous oxide (N2O). These N2O emissions stem from inefficient utilisation of nitrogen (N) ingested by ruminants, and the inability of pasture to utilise the deposited N. Predicted growth in dairy and meat consumption means that there is a requirement to quantify N2O emissions, and investigate emission reduction mechanisms. Three 12 month 'seasonal' experiments were undertaken at Crichton, SW Scotland, where N2O emissions were measured from applications of cattle urine, dung, artificial urine and urine+a nitrification inhibitor (NI), dicyandiamide (DCD). The three application timings were 'spring', 'summer' and 'autumn', representative of early-, mid- and late grazing seasons. N2O emissions were measured from static chambers for 12 months. The aim was to quantify emissions from cattle excreta, and determine their dependence on the season of application, and the respective contribution of dung and urine to total excreta emissions. Measurement from NI amended urine was made to assess DCD's potential as an emission mitigation tool. Emissions were compared to the IPCC's default emission factor (EF) of 2% for cattle excreted N. Mean annual cumulative emissions from urine were the highest when applied in summer (5034 g N2O-N ha(-1)), with lower emissions from spring (1903 g N2O-N ha(-1)) and autumn (2014 g N2O-N ha(-1)) application, most likely due to higher temperatures and soil moisture conducive to both nitrification and denitrification in the summer months. Calculated EFs were significantly greater from urine (1.1%) than dung (0.2%) when excreta was applied in summer, and EFs varied with season of application, but in all experiments were lower than the IPCC default of 2%. These results support both lowering and disaggregating this EF into individual EFs for dung and urine. Addition of DCD to urine caused no significant reduction in emissions, suggesting that more research is required into its use as a mitigation option.

Glycaemic control is harder to achieve than blood pressure or lipid control in Irish adults with type 1 diabetes.

We sought to determine the attainment of targets for glycaemic control and vascular risk reduction in an Irish cohort of T1DM adults. Of 797 patients (53% male, mean age 40.3 ± 14.8 years, HbA1c 8.5 ± 1.6% (69.6 ± 17.8 mmol mol(-1))), 15%, 68% and 62% achieved targets for HbA1c, blood pressure and LDL cholesterol, respectively.

Methane emissions among individual dairy cows during milking quantified by eructation peaks or ratio with carbon dioxide.

The aims of this study were to compare methods for examining measurements of CH4 and CO2 emissions of dairy cows during milking and to assess repeatability and variation of CH4 emissions among individual dairy cows. Measurements of CH4 and CO2 emissions from 36 cows were collected in 3 consecutive feeding periods. In the first period, cows were fed a commercial partial mixed ration (PMR) containing 69% forage. In the second and third periods, the same 36 cows were fed a high-forage PMR ration containing 75% forage, with either a high grass silage or high maize silage content. Emissions of CH4 during each milking were examined using 2 methods. First, peaks in CH4 concentration due to eructations during milking were quantified. Second, ratios of CH4 and CO2 average concentrations during milking were calculated. A linear mixed model was used to assess differences between PMR. Variation in CH4 emissions was observed among cows after adjusting for effects of lactation number, week of lactation, diet, individual cow, and feeding period, with coefficients of variation estimated from variance components ranging from 11 to 14% across diets and methods of quantifying emissions. No significant difference was detected between the 3 PMR in CH4 emissions estimated by either method. Emissions of CH4 calculated from eructation peaks or as CH4 to CO2 ratio were positively associated with forage dry matter intake. Ranking of cows according to CH4 emissions on different diets was correlated for both methods, although rank correlations and repeatability were greater for CH4 concentration from eructation peaks than for CH4-to-CO2 ratio. We conclude that quantifying enteric CH4 emissions either using eructation peaks in concentration or as CH4-to-CO2 ratio can provide highly repeatable phenotypes for ranking cows on CH4 output.

Variation in enteric methane emissions among cows on commercial dairy farms.

Methane (CH4) emissions by dairy cows vary with feed intake and diet composition. Even when fed on the same diet at the same intake, however, variation between cows in CH4 emissions can be substantial. The extent of variation in CH4 emissions among dairy cows on commercial farms is unknown, but developments in methodology now permit quantification of CH4 emissions by individual cows under commercial conditions. The aim of this research was to assess variation among cows in emissions of eructed CH4 during milking on commercial dairy farms. Enteric CH4 emissions from 1964 individual cows across 21 farms were measured for at least 7 days/cow using CH4 analysers at robotic milking stations. Cows were predominantly of Holstein Friesian breed and remained on the same feeding systems during sampling. Effects of explanatory variables on average CH4 emissions per individual cow were assessed by fitting a linear mixed model. Significant effects were found for week of lactation, daily milk yield and farm. The effect of milk yield on CH4 emissions varied among farms. Considerable variation in CH4 emissions was observed among cows after adjusting for fixed and random effects, with the CV ranging from 22% to 67% within farms. This study confirms that enteric CH4 emissions vary among cows on commercial farms, suggesting that there is considerable scope for selecting individual cows and management systems with reduced emissions.

The effect of changing cow production and fitness traits on net income and greenhouse gas emissions from Australian dairy systems.

The aim of this study was to compare the effect of changing a range of biological traits on farm net income and greenhouse gas emissions (expressed in carbon dioxide equivalents, CO2-eq.) in the Australian dairy cow population. An average cow was modeled, using breed-average information for Holsteins and Jerseys from the Australian Dairy Herd Improvement Scheme. A Markov chain approach was used to describe the steady-state herd structure, as well as estimate the CO2-eq. emissions per cow and per kilogram of milk solids. The effects of a single unit change in herd milk volume, fat and protein yields, live weight, survival, dry matter intake, somatic cell count, and calving interval were assessed. With the traits studied, the only single-unit change that would bring about a desirable increase in both net income and reduced emissions intensity per cow and per kilogram of milk solids in Australian dairy herds would be an increase in survival and reductions in milk volume, live weight, DMI, SCC, and calving interval. The models developed can be used to assess lifetime dairy system abatement options by breeding, feeding, and management. Selective breeding and appropriate management can both improve health, fertility, and feed utilization of Australian dairy systems and reduce its environmental impact.

Limb lengthening in congenital posteromedial bow of the tibia.

Congenital posteromedial bowing of the tibia (PMBT) is a rare condition affecting one lower limb. The bowing of the tibia usually resolves; however, there is associated limb length discrepancy (LLD), which often persists and can cause functional deficits. Advances in limb lengthening techniques allow this issue to be addressed, often with concomitant angular deformity correction. This study examined eleven patients who have had limb lengthening procedures with mean pre-operative LLD of 3.7 cm (range 1.5-5 cm), mean increase in length was 3.9 cm (range 1.5-5.8 cm), and mean LLD at last follow-up was less than 0.6 cm (range 0-2.0 cm). The main complications were minor or moderate grades, such as pin site infection. Greater LLD was found than previously reported, and we believe that the tertiary referrals were those of a severe form of PMBT. The authors conclude that in view of deformity with discrepancy, in select cases, correction and lengthening would be an option rather than only contralateral epiphysiodesis.

A generic model of growth, energy metabolism, and body composition for cattle and sheep.

A generic daily time-step model of animal growth and metabolism for cattle and sheep is described. It includes total BW as well as protein, water, and fat components, and also energy components associated with the growth of protein and fat, and activity costs. Protein decay is also incorporated, along with the energy costs of resynthesising degraded protein. Protein weight is taken to be the primary indicator of metabolic state, and fat is regarded as a potential source of metabolic energy for physiological processes such as the resynthesis of degraded protein. Normal weight is defined as maximum protein and the associated fat component so that if the BW of the animal exceeds the normal value, all excess weight is in the form of fat. It is assumed that the normal fat fraction increases from birth to maturity. There are relatively few parameters, all of which have a reasonable physiological interpretation, which helps simplify choosing parameters for different animal types and breeds. Simulations for growing and mature cattle and sheep in response to varying available ME are presented and comparisons with empirical curves reported in the literature for body composition are in excellent agreement.

Increased CSF concentrations of myelin basic protein after TBI in infants and children: absence of significant effect of therapeutic hypothermia.

BACKGROUND: The objectives of this study were to determine effects of severe traumatic brain injury (TBI) on cerebrospinal fluid (CSF) concentrations of myelin basic protein (MBP) and to assess relationships between clinical variables and CSF MBP concentrations. METHODS: We measured serial CSF MBP concentrations in children enrolled in a randomized controlled trial evaluating therapeutic hypothermia (TH) after severe pediatric TBI. Control CSF was obtained from children evaluated, but found not to be having CNS infection. Generalized estimating equation models and Wilcoxon Rank-Sum test were used for comparisons of MBP concentrations. RESULTS: There were 27 TBI cases and 57 controls. Overall mean (± SEM) TBI case MBP concentrations for 5 days after injury were markedly greater than controls (50.49 ± 6.97 vs. 0.11 ± 0.01 ng/ml, p < 0.01). Mean MBP concentrations were lower in TBI patients <1 year versus >1 year (9.18 ± 1.67 vs. 60.22 ± 8.26 ng/ml, p = 0.03), as well as in cases with abusive head trauma (AHT) versus non-abusive TBI (14.46 ± 3.15 vs. 61.17 ± 8.65 ng/ml, p = 0.03). TH did not affect MBP concentrations. CONCLUSIONS: Mean CSF MBP increases markedly after severe pediatric TBI, but is not affected by TH. Infancy and AHT are associated with low MBP concentrations, suggesting that age-dependent myelination influences MBP concentrations after injury. Given the magnitude of MBP increases, axonal injury likely represents an important therapeutic target in pediatric TBI.

Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates.

PURPOSE: Osteogenesis imperfecta (OI) has been treated with bisphosphonates for many years, with some clear clinical benefits. In adults, there are reports of a new pattern of atraumatic subtrochanteric fractures with bisphosphonate treatment. This study assesses if bisphosphonate treatment leads to an altered pattern of femoral fractures. METHODS: Retrospective review of imaging for a cohort of 176 bisphosphonate-treated OI patients to identify the locations of femoral fractures over a two-year period, as compared to a historical control group managed pre-bisphosphonates. RESULTS: Sixteen femoral fractures were identified in this time period in the bisphosphonate-treated group. All but two were within the subtrochanteric region. In comparison, the historical group-composed of 26 femoral fractures-had a more widespread fracture pattern, with the most frequent location being the mid-diaphysis. Many of the subtrochanteric fractures in the treatment group occurred with minimal trauma. CONCLUSIONS: It appears that concerns over the treatment of the adult osteoporotic population with bisphosphonates are amplified and mirrored in OI. It is possible that the high bending moments in the proximal femur together with altered mechanical properties of cortical bone secondary to the use of this group of drugs increase the risk of this type of injury, which warrants further modification of surgical management of the femur.

The effect of improving cow productivity, fertility, and longevity on the global warming potential of dairy systems.

This study compared the environmental impact of a range of dairy production systems in terms of their global warming potential (GWP, expressed as carbon dioxide equivalents, CO(2)-eq.) and associated land use, and explored the efficacy of reducing said impact. Models were developed using the unique data generated from a long-term genetic line × feeding system experiment. Holstein-Friesian cows were selected to represent the UK average for milk fat plus protein production (control line) or were selected for increased milk fat plus protein production (select line). In addition, cows received a low forage diet (50% forage) with no grazing or were on a high forage (75% forage) diet with summer grazing. A Markov chain approach was used to describe the herd structure and help estimate the GWP per year and land required per cow for the 4 alternative systems and the herd average using a partial life cycle assessment. The CO(2)-eq. emissions were expressed per kilogram of energy-corrected milk (ECM) and per hectare of land use, as well as land required per kilogram of ECM. The effects of a phenotypic and genetic standard deviation unit improvement on herd feed utilization efficiency, ECM yield, calving interval length, and incidence of involuntary culling were assessed. The low forage (nongrazing) feeding system with select cows produced the lowest CO(2)-eq. emissions of 1.1 kg/kg of ECM and land use of 0.65 m(2)/kg of ECM but the highest CO(2)-eq. emissions of 16.1t/ha of the production systems studied. Within the herd, an improvement of 1 standard deviation in feed utilization efficiency was the only trait of those studied that would significantly reduce the reliance of the farming system on bought-in synthetic fertilizer and concentrate feed, as well as reduce the average CO(2)-eq. emissions and land use of the herd (both by about 6.5%, of which about 4% would be achievable through selective breeding). Within production systems, reductions in CO(2)-eq. emissions per kilogram of ECM and CO(2)-eq. emissions per hectare were also achievable by an improvement in feed utilization. This study allowed development of models that harness the biological trait variation in the animal to improve the environmental impact of the farming system. Genetic selection for efficient feed use for milk production according to feeding system can bring about reductions in system nutrient requirements, CO(2)-eq. emissions, and land use per unit product.

Charcoal addition to soils in NE England: a carbon sink with environmental co-benefits?

Interest in the application of biochar (charcoal produced during the pyrolysis of biomass) to agricultural land is increasing across the world, recognised as a potential way to capture and store atmospheric carbon. Its interest is heightened by its potential co-benefits for soil quality and fertility. The majority of research has however been undertaken in tropical rather than temperate regions. This study assessed the potential for lump-wood charcoal addition (as a substitute for biochar) to soil types which are typically under arable and forest land-use in North East England. The study was undertaken over a 28 week period and found: i) No significant difference in net ecosystem respiration (NER) between soils containing charcoal and those without, other than in week 1 of the trial. ii) A significantly higher dissolved organic carbon (DOC) flux from soils containing large amounts of charcoal than from those untreated, when planted with ryegrass. iii) That when increased respiration or DOC loss did occur, neither was sufficiently large to alter the carbon sink benefits of charcoal application. iv) That charcoal incorporation resulted in a significantly lower nitrate flux in soil leachate from mineral soils. v) That charcoal incorporation caused significant increases in soil pH, from 6.98 to 7.22 on bare arable soils when 87,500 kg charcoal/ha was applied. Consideration of both the carbon sink and environmental benefits observed here suggests that charcoal application to temperate soils typical of North East England should be considered as a method of carbon sequestration. Before large scale land application is encouraged, further large scale trials should be undertaken to confirm the positive results of this research.

Risk factors for culling in Holstein-Friesian dairy cows.

Risk factors associated with voluntary and involuntary culling within a Holstein-Friesian dairy cow research herd were identified. Data were studied from 3498 completed lactations from the Langhill Holstein-Friesian dairy herd between January 1990 and June 2008. During this period the cows were based on two different farms in Scotland. The culling rate of the milking herd was approximately 25 per cent per annum. Approximately 68 per cent of cows culled were classified as involuntary. The association between different risk factors and the incidence of culling was investigated using a general linear mixed model. Of the 838 cows culled, 59 per cent were culled before the fourth lactation. Culling was associated with cows that had an assisted calving (P<0.01), aborted (P<0.01) and/or suffered from mastitis (P<0.05). Cows that were culled were also more likely to be older cows (P<0.01), have a low number of milking days (P<0.001) and/or a greater number of days from calving to conception (P<0.01). Culling was also associated with conception failure (r=0.752, P<0.001). Further work might help reduce the number of animals culled involuntarily, by identifying key factors associated with the incidence of an assisted calving, abortion and mastitis, and improving milking and fertility performance using detailed data from the Langhill herd.

Energy transfer between CdS nanocrystals and neodymium ions embedded in vitreous substrates.

Experimental evidence has been observed for energy transfer from CdS nanocrystals, synthesized by the fusion method, to Nd(3+) ions embedded in vitreous substrates. These dot samples doped with neodymium have been investigated by combined optical absorption (OA), photoluminescence (PL), and time-resolved photoluminescence (PLRT) techniques. Radiative and nonradiative energy transfers between CdS dot and Nd(3+) ion levels, to our knowledge not reported before, can be clearly observed in the PL spectra where the emission band valleys correspond exactly to the energy absorption peaks of the doping ion. The PLRT data reinforce these energy transfer mechanisms in which the increasing overlap between the CdS PL band and the OA to the Nd(3+) levels decreases stimulated emissions from the doping ions.

Assessing the probability of carbon and greenhouse gas benefit from the management of peat soils.

This study proposes a method for assessing the probability that land management interventions will lead to an improvement in the carbon sink represented by peat soils. The method is able to: combine studies of different carbon uptake and release pathways in order to assess changes on the overall carbon or greenhouse gas budget; calculate the probability of the management or restoration leading to an improvement in the budget; calculate the uncertainty in that probability estimate; estimate the equivalent number of complete budgets available from the combination of the literature; test the difference in the outcome of different land management interventions; and provide a method for updating the predicted probabilities as new studies become available. Using this methodology, this study considered the impact of: afforestation, managed burning, drainage, drain-blocking, grazing removal; and revegetation, on the carbon budget of peat soils in the UK. The study showed that afforestation, drain-blocking, revegetation, grazing removal and cessation of managed burning would bring a carbon benefit, whereas deforestation, managed burning and drainage would bring a disbenefit. The predicted probabilities of a benefit are often equivocal as each management type or restoration often leads to increase in uptake in one pathway while increasing losses in another.

Enhancement of inflammatory mediator release by beta(2)-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action.

BACKGROUND AND PURPOSE: Due to their potent bronchodilator properties, beta(2)-adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of beta(2)-adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of beta(2)-adrenoceptor agonists on inflammatory mediator release. EXPERIMENTAL APPROACH: Transcription factor activation, and both release and mRNA expression of IL-6 and IL-8 were examined by luciferase reporter assay, elisa and real-time RT-PCR in bronchial human epithelial BEAS-2B cells or primary human bronchial epithelial cells grown at an air-liquid interface. KEY RESULTS: Pre-incubation with beta(2)-adrenoceptor agonists (salbutamol, salmeterol, formoterol) augmented the release and mRNA expression of IL-6 and IL-8 induced by IL-1beta and IL-1beta plus histamine, whereas NF-kappaB-dependent transcription was significantly repressed, and AP-1-dependent transcription was unaffected. These effects were mimicked by other cAMP-elevating agents (PGE(2), forskolin). Enhancement of cytokine release by beta(2)-adrenoceptor agonists also occurred in primary bronchial epithelial cells. Addition of dexamethasone with salmeterol repressed IL-6 and IL-8 release to levels that were similar to the repression achieved in the absence of salmeterol. IL-6 release was enhanced when salmeterol was added before, concurrently or after IL-1beta plus histamine stimulation, whereas IL-8 release was only enhanced by salmeterol addition prior to stimulation. CONCLUSIONS AND IMPLICATIONS: Enhancement of IL-6 and IL-8 release may contribute to the deleterious effects of beta(2)-adrenoceptor agonists in asthma. As increased inflammatory mediator expression is prevented by the addition of glucocorticoid to the beta(2)-adrenoceptor, our data provide further mechanistic support for the use of combination therapies in asthma management.