Effect of High-Dose Esomeprazole on CYP1A2, CYP2C19, and CYP3A4 Activities in Humans : Evidence for Substantial and Long-lasting Inhibition of CYP2C19

In vitro, esomeprazole is a time-dependent inhibitor of CYP2C19. Additionally, racemic omeprazole induces CYP1A2 and omeprazole and its metabolites inhibit CYP3A4in vitro. In this 5-phase study, 10 healthy volunteers ingested 20 mg pantoprazole, 0.5 mg midazolam, and 50 mg caffeine as respective index substrates for CYP2C19, 3A4, and 1A2 before and 1, 25, 49 (pantoprazole only), and 73 hours after an 8-day pretreatment with 80 mg esomeprazole twice daily. The area under the plasma concentration-time curve (AUC) ofR-pantoprazole increased 4.92-fold (90% confidence interval (CI) 3.55-6.82), 2.31-fold (90% CI 1.85-2.88), and 1.33-fold (90% CI 1.06-1.68) at the 1-hour, 25-hour, and 73-hour phases, respectively, consistent with a substantial and persistent inhibition of CYP2C19. The AUC of midazolam increased up to 1.44-fold (90% CI 1.22-1.72) and the paraxanthine/caffeine metabolic ratio up to 1.19-fold (90% CI 1.04-1.36), when the index substrates were taken 1 hour after esomeprazole. Based on the recovery ofR-pantoprazole oral clearance, the turnover half-life of CYP2C19 was estimated to average 53 hours. Pharmacokinetic simulation based on the observed concentrations of esomeprazole and its metabolites as well as their published CYP2C19 inhibitory constants was well in line with the observed changes inR-pantoprazole pharmacokinetics during the course of the study. Extrapolations assuming linear pharmacokinetics of esomeprazole suggested weak to moderate inhibition at 20 and 40 mg twice daily dosing. In conclusion, high-dose esomeprazole can cause strong inhibition of CYP2C19, but only weakly inhibits CYP3A4 and leads to minor induction of CYP1A2. The enzymatic activity of CYP2C19 recovers gradually in similar to 3-4 days after discontinuation of esomeprazole treatment.Peer reviewe

Assessing extraction trail trafficability using harvester CAN-bus data

Modern forest machines with a Controlled Area Network (CAN)-bus managed diesel engine and hydrostatic transmission can continuously measure power expended in traveling. At a constant speed on level ground, the power is expended in overcoming motion resistance, which is directly related to wheel sinkage and hence to site trafficability. In cut-to-length timber harvesting, the harvester precedes the forwarder on the site, making it feasible to utilize the harvester to collect data on site trafficability to produce a trafficability map for the forwarder. CAN-bus trafficability mapping was tested with an 8-wheeled Ponsse Scorpion King harvester and an 8-wheeled Ponsse Elk forwarder instrumented for collecting transmission power expenditure, in addition to appropriate available CAN-bus information. Trafficability was also mapped based solely on momentary engine power in order to eliminate the need for additional pressure transducers. The CANbus data showed good results for mapping site trafficability when compared to soil penetration resistance and harvesting machinery wheel rut depth measurements. Assessing harvester rolling resistance using CAN-bus data offers an interesting possibility to map harvesting site trafficability also in Big Data scale. Since modern harvesters are practically ready for indirect power recording, the additional cost of fully automated and comprehensive trafficability mapping as part of operative forestry is negligible

Could continuous cover forestry be an economically and environmentally feasible management option on drained boreal peatlands?

Environmental and economic performance of forestry on drained peatlands was reviewed to consider whether continuous cover forestry (CCF) could be a feasible alternative to even-aged management (EM). CCF was regarded feasible particularly because continuously maintaining a tree stand with significant transpiration and interception capacity would decrease the need for ditch network maintenance. Managing CCF forests in such a way that the ground water levels are lower than in clear-cut EM forests but higher than in mature EM forests could decrease greenhouse gas emissions and negative water quality impacts caused both by anoxic redox reactions and oxidation and mineralization of deep peat layers. Regeneration studies indicated potential for satisfactory natural regeneration under CCF on drained peatlands. An economic advantage in CCF over EM is that fewer investments are needed to establish the forest stand and sustain its growth. Thus, even if the growth of trees in CCF forests were lower than in EM forests, CCF could at least in some peatland sites turn out to be a more profitable forest management regime. An advantage of CCF from the viewpoint of socially optimal forest management is that it plausibly reduces the negative externalities of management compared to EM. We propose that future research in drained peatland forests should focus on assessing the economic and environmental feasibility of CCF.Peer reviewe

Nitrous oxide emissions from a beech forest floor measured by eddy covariance and soil enclosure technigues

Peer reviewe

Effect of High-Dose Esomeprazole on CYP1A2, CYP2C19, and CYP3A4 Activities in Humans: Evidence for Substantial and Long-lasting Inhibition of CYP2C19

In vitro, esomeprazole is a time-dependent inhibitor of CYP2C19. Additionally, racemic omeprazole induces CYP1A2 and omeprazole and its metabolites inhibit CYP3A4in vitro. In this 5-phase study, 10 healthy volunteers ingested 20 mg pantoprazole, 0.5 mg midazolam, and 50 mg caffeine as respective index substrates for CYP2C19, 3A4, and 1A2 before and 1, 25, 49 (pantoprazole only), and 73 hours after an 8-day pretreatment with 80 mg esomeprazole twice daily. The area under the plasma concentration-time curve (AUC) ofR-pantoprazole increased 4.92-fold (90% confidence interval (CI) 3.55-6.82), 2.31-fold (90% CI 1.85-2.88), and 1.33-fold (90% CI 1.06-1.68) at the 1-hour, 25-hour, and 73-hour phases, respectively, consistent with a substantial and persistent inhibition of CYP2C19. The AUC of midazolam increased up to 1.44-fold (90% CI 1.22-1.72) and the paraxanthine/caffeine metabolic ratio up to 1.19-fold (90% CI 1.04-1.36), when the index substrates were taken 1 hour after esomeprazole. Based on the recovery ofR-pantoprazole oral clearance, the turnover half-life of CYP2C19 was estimated to average 53 hours. Pharmacokinetic simulation based on the observed concentrations of esomeprazole and its metabolites as well as their published CYP2C19 inhibitory constants was well in line with the observed changes inR-pantoprazole pharmacokinetics during the course of the study. Extrapolations assuming linear pharmacokinetics of esomeprazole suggested weak to moderate inhibition at 20 and 40 mg twice daily dosing. In conclusion, high-dose esomeprazole can cause strong inhibition of CYP2C19, but only weakly inhibits CYP3A4 and leads to minor induction of CYP1A2. The enzymatic activity of CYP2C19 recovers gradually in similar to 3-4 days after discontinuation of esomeprazole treatment

Net precipitation over the Baltic Sea for one year using several methods

Precipitation and evaporation over the Baltic Sea are calculated for a one-year period from September 1998 to August 1999 by four different tools, the two atmospheric regional models HIRLAM and REMO, the oceanographic model PROBE-Baltic in combination with the SMHI (1 × 1)° database and Interpolated Fields, based essentially on ship measurements. The investigated period is slightly warmer and wetter than the climatological mean. Correlation coefficients of the differently calculated latent heat fluxes vary between 0.81 (HIRLAM and REMO) and 0.56 (SMHI/PROBE-Baltic and Interpolated Fields), while the correlation coefficients between model fluxes and measured fluxes range from 0.61 and 0.78. Deviations of simulated and interpolated monthly precipitation over the Baltic Sea are less than ±5 mm in the southern Baltic and up to 20 mm near the Finnish coast for the one-year period. The methods simulate the annual cycle of precipitation and evaporation of the Baltic Proper in a similar manner with a broad maximum of net precipitation in spring and early summer and a minimum in late summer. The annual averages of net precipitation of the Baltic Proper range from 57 mm (REMO) to 262 mm (HIRLAM) and for the Baltic Sea from 96 mm (SMHI/PROBE-Baltic) to 209 mm (HIRLAM). This range is considered to give the uncertainty of present-day determination of the net precipitation over the Baltic Sea

Dynamic forest trafficability prediction by fusion of open data, hydrologic forecasts and harvester-measured data

FOTETRAF project: www.luke.fi/projektit/fotetraf-sa-paatos-295337. Posteri esillä Marcus Wallenberg-palkintoseremonian yhteydessä pidettävässä nuorten tutkijoiden seminaarissa 26-27.10.2017 Tukholmassa (http://www.mwp.org/yr/).201

Is the water footprint an appropriate tool for forestry and forest products: The Fennoscandian case

The water footprint by the Water Footprint Network (WF) is an ambitious tool for measuring human appropriation and promoting sustainable use of fresh water. Using recent case studies and examples from water-abundant Fennoscandia, we consider whether it is an appropriate tool for evaluating the water use of forestry and forest-based products. We show that aggregating catchment level water consumption over a product life cycle does not consider fresh water as a renewable resource and is inconsistent with the principles of the hydrologic cycle. Currently, the WF assumes that all evapotranspiration (ET) from forests is a human appropriation of water although ET from managed forests in Fennoscandia is indistinguishable from that of unmanaged forests. We suggest that ET should not be included in the water footprint of rain-fed forestry and forest-based products. Tools for sustainable water management should always contextualize water use and water impacts with local water availability and environmental sensitivity

Evaluating the performance of land surface model ORCHIDEE-CAN v1.0 on water and energy flux estimation with a single- and multi-layer energy budget scheme

Canopy structure is one of the most important vegetation characteristics for land-atmosphere interactions, as it determines the energy and scalar exchanges between the land surface and the overlying air mass. In this study we evaluated the performance of a newly developed multilayer energy budget in the ORCHIDEE-CAN v1.0 land surface model (Organising Carbon and Hydrology In Dynamic Ecosystems - CANopy), which simulates canopy structure and can be coupled to an atmospheric model using an implicit coupling procedure. We aim to provide a set of accept-able parameter values for a range of forest types. Top-canopy and sub-canopy flux observations from eight sites were collected in order to conduct this evaluation. The sites crossed climate zones from temperate to boreal and the vegetation types included deciduous, evergreen broad-leaved and evergreen needle-leaved forest with a maximum leaf area index (LAI; all-sided) ranging from 3.5 to 7.0. The parametrization approach proposed in this study was based on three selected physical processes - namely the diffusion, advection, and turbulent mixing within the canopy. Short-term sub-canopy observations and long-term surface fluxes were used to calibrate the parameters in the sub-canopy radiation, turbulence, and resistance modules with an automatic tuning process. The multi-layer model was found to capture the dynamics of sub-canopy turbulence, temperature, and energy fluxes. The performance of the new multi-layer model was further compared against the existing single-layer model. Although the multi-layer model simulation results showed few or no improvements to both the nighttime energy balance and energy partitioning during winter compared with a single-layer model simulation, the increased model complexity does provide a more detailed description of the canopy micrometeorology of various forest types. The multi-layer model links to potential future environmental and ecological studies such as the assessment of in-canopy species vulnerability to climate change, the climate effects of disturbance intensities and frequencies, and the consequences of biogenic volatile organic compound (BVOC) emissions from the terrestrial ecosystem.Peer reviewe