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  • Articles  (762)
  • pharmacokinetics  (321)
  • wheat  (245)
  • 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
  • 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry
  • 04. Solid Earth::04.06. Seismology::04.06.06. Surveys, measurements, and monitoring
  • 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
  • 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
  • Immunocytochemistry
  • Mt. Etna
  • Springer  (760)
  • Copernicus
  • University of Patras, Greece
  • 2005-2009  (24)
  • 1995-1999  (685)
  • 1970-1974  (53)
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  • Articles  (762)
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  • 1
    Publication Date: 2020-11-23
    Description: Abstract: The simultaneous solution of the Planck equation (involving the widely used “dual-band” technique) using two shortwave infrared (SWIR) bands allows for an estimate of the fractional area of the hottest part of an active lava flow (fh), and the background temperature of the cooler crust (Tc). The use of a high spectral and spatial resolution imaging spectrometer with a wide dynamic range of 15 bits (DAIS 7915) in the wavelength range from 0.501 to 12.67 µm resulted in the identification of crustal temperature and fractional areas for an intra-crater hot spot at Mount Etna, Italy. This study indicates the existence of a relationship between these Tc and fh extracted from DAIS and Landsat TM data. When the dual band equation system is performed on a lava flow, a logarithmic distribution is obtained from a plot of the fractional area of the hottest temperature versus the temperature of the cooler crust. An entirely different distribution is obtained over active degassing vents, where increases in Tc occur without any increase in fh. This result indicates that we can use scatter plots of Tc vs. fh to discriminate between different types of volcanic activity, in this case between degassing vents and lava flows, using satellite thermal data.
    Description: Published
    Description: 641–651
    Description: 4V. Processi pre-eruttivi
    Description: JCR Journal
    Description: open
    Keywords: Mount Etna ; remote-sensing ; lava-flow ; degassing vent ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
    Publication Date: 2017-04-04
    Description: The Monte Nuovo eruption is the most recent event that occurred at Phlegrean Fields (Italy) and lasted from 29 September to 6 October 1538. It was characterized by 2 days of quasi-sustained phreatomagmatic activity generating pumice-bearing pyroclastic density currents and forming a 130-m-high tuff cone (Lower Member deposits). The activity resumed after a pause of 2 days with two discrete Vulcanian explosions that emplaced radially distributed, scoria-bearing pyroclastic flows (Upper Member deposits). The juvenile products of Lower and Upper Members are, respectively, phenocryst-poor, light-coloured pumice and dark scoria fragments with K-phonolitic bulk compositions, identical in terms of both major and trace elements. Groundmass is formed by variable proportions of K-feldspar and glass, along with minor sodalite and Fe-Ti oxide present in the most crystallized samples. Investigations of groundmass compositions and textures were performed to assess the mechanisms of magma ascent, degassing and fragmentation along the conduit and implications for the eruptive dynamics. In pumice of the Lower Member groundmass crystal content increases from 13 to 28 vol% from the base to the top of the sequence. Products of the Upper Member consist of clasts with a groundmass crystal content between 30 and 40 vol% and of totally crystallized fragments. Crystal size distributions of groundmass feldspars shift from a single population at the base of the Lower Member to a double population in the remaining part of the sequence. The average size of both populations regularly increases from the Lower to the Upper Member. Crystal number density increases by two orders of magnitude from the Lower to the Upper Member, suggesting that nucleation dominated during the second phase of the eruption. The overall morphological, compositional and textural data suggest that the juvenile components of the Monte Nuovo eruption are likely to record variations of the magma properties within the conduit. The different textures of pumice clasts from the Lower Member possibly reflect horizontal gradients of the physical properties (P, T) of the ascending magma column, while scoriae from the second phase are thought to result from the disruption of a slowly rising plug crystallizing in response to degassing. In particular, crystal size distribution data point to syn-eruptive degassing-induced crystallization as responsible for the transition in eruptive style from the first to the second phase of the eruption. This mechanism not only has been proved to profoundly affect the dynamics of dome-forming calc-alkaline eruptions, but may also have a strong influence in driving the eruption dynamics of alkaline magmas of intermediate to evolved compositions.
    Description: Published
    Description: 601-621
    Description: reserved
    Keywords: Phlegrean Fields ; Vulcanian explosion ; Degassing ; Groundmass crystallization ; Eruption dynamics ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.02. Experimental volcanism ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 3
    Publication Date: 2017-04-04
    Description: Volcanic hazard assessment is a basic ingredient for risk-based decision-making in land-use planning and emergency management. Volcanic hazard is defined as the probability of any particular area being affected by a destructive volcanic event within a given period of time (Fournier d’Albe 1979). The probabilistic nature of such an important issue derives from the fact that volcanic activity is a complex process, characterized by several and usually unknown degrees of freedom that are often linked by nonlinear relationships (e.g. Bak et al. 1988). Except in sporadic cases, the result of this complexity is an intrinsic, and perhaps unavoidable, unpredictability of the time evolution of the volcanic system from a deterministic point of view.
    Description: Published
    Description: open
    Keywords: model ; volcanic risk ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book
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  • 4
    Publication Date: 2017-04-04
    Description: The main purpose of this paper is to introduce a Bayesian event tree model for eruption forecasting (BET EF). The model represents a flexible tool to provide probabilities of any specific event at which we are interested in, by merging all the relevant available information, such as theoretical models, a priori beliefs, monitoring measures, and any kind of past data. BET EF is based on a Bayesian procedure and it relies on the fuzzy approach to manage monitoring data. The method deals with short- and long-term forecasting, therefore it can be useful in many practical aspects, as land use planning, and during volcanic emergencies. Finally, we provide the description of a free software package that provides a graphically supported computation of short- to long-term eruption forecasting, and a tutorial application to the recent MESIMEX exercise at Vesuvius.
    Description: Published
    Description: on line first
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: JCR Journal
    Description: partially_open
    Keywords: Eruption forecasting ; Long- and short-term volcanic hazard ; Bayesian inference ; Event tree ; Fuzzy sets ; MESIMEX ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 5
    Publication Date: 2017-04-04
    Description: Six hundred and sixty-seven water samples were collected from public drinking water supplies in Sicily and analysed for electric conductivity and for their Cl-, Br- and F- contents. The samples were, as far as possible, collected evenly over the entire territory with an average sampling density of about one sample for every 7600 inhabitants. The contents of Cl- and Br-, ranging between 5.53 and 1302 mg/l and between 〈 0.025 and 4.76 mg/l respectively, correlated well with the electric conductivity, a parameter used as a proxy for water salinity. The highest values were found both along the NW and SE coasts, which we attributed to seawater contamination, and in the central part of Sicily, which we attributed to evaporitic rock dissolution. The fluoride concentrations ranged from 0.023 to 3.28 mg/l, while the highest values (only 3 exceeding the maximum admissible concentration of 1.5 mg/l) generally correlated either with the presence in the area of crystalline (volcanic or metamorphic) or evaporitic rocks or with contamination from hydrothermal activity. Apart from these limited cases of exceeding F- levels, the waters of public drinking water supplies in Sicily can be considered safe for human consumption for the analysed parameters. Some limited concern could arise from the intake of bromide-rich waters (about 3% exceeding 1 mg/l) because of the potential formation of dangerous disinfection by-products.
    Description: Published
    Description: 303-313
    Description: 4.4. Scenari e mitigazione del rischio ambientale
    Description: JCR Journal
    Description: reserved
    Keywords: drinking water quality ; fluoride ; bromide ; chloride ; 03. Hydrosphere::03.02. Hydrology::03.02.04. Measurements and monitoring ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 6
    Publication Date: 2017-04-04
    Description: Microgravity observations at Mt. Etna have been routinely performed as both discrete (since 1986) and continuous (since 1998) measurements. In addition to describing the methodology for acquiring and reducing gravity data from Mt. Etna, this paper provides a collection of case studies aimed at demonstrating the potential of microgravity to investigate the plumbing system of an active volcano and detect forerunners to paroxysmal volcanic events. For discrete gravity measurements, results from 1994– 1996 and 2001 are reported. During the first period, the observed gravity changes are interpreted within the framework of the Strombolian activity which occurred from the summit craters. Gravity changes observed during the first nine months of 2001 are directly related to subsurface mass redistributions which preceded, accompanied and followed the July-August 2001 flank eruption of Mt. Etna. Two continuous gravity records are discussed: a 16-month (October 1998 to February 2000) sequence and a 48-hour (26–28 October, 2002) sequence, both from a station within a few kilometers of the volcano’s summit. The 16-month record may be the longest continuous gravity sequence ever acquired at a station very close to the summit zone of an active volcano. By cross analyzing it with contemporaneous discrete observations along a summit profile of stations, both the geometry of a buried source and its time evolution can be investigated. The shorter continuous sequence encompasses the onset of an eruption from a location only 1.5 km from the gravity station. This gravity record is useful for establishing constraints on the characteristics of the intrusive mechanism leading to the eruption. In particular, the observed gravity anomaly indicates that the magma intrusion occurred ‘‘passively’’ within a fracture system opened by external forces.
    Description: Published
    Description: 769-790
    Description: 2.6. TTC - Laboratorio di gravimetria, magnetismo ed elettromagnetismo in aree attive
    Description: JCR Journal
    Description: reserved
    Keywords: Mt. Etna ; microgravity ; 04. Solid Earth::04.03. Geodesy::04.03.05. Gravity variations
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 7
    Publication Date: 2017-04-04
    Description: Mount Etna is an open conduit volcano, characterised by persistent activity, consisting of degassing and explosive phenomena at summit craters, frequent flank eruptions, and more rarely, eccentric eruptions. All eruption typologies can give rise to lava flows, which represent the greatest hazard by the volcano to the inhabited areas. Historical documents and scientific papers related to the 20th century effusive activity have been examined in detail, and volcanological parameters have been compiled in a database. The cumulative curve of emitted lava volume highlights the presence of two main eruptive periods: (a) the 1900–1971 interval, characterised by a moderate slope of the curve, amounting to 436 · 106 m3 of lava with average effusion rate of 0.2 m3/s and (b) the 1971–1999 period, in which a significant increase in eruption frequency is associated with a large issued lava volume (767 · 106 m3) and a higher effusion rate (0.8 m3/s). The collected data have been plotted to highlight different eruptive behaviour as a function of eruptive periods and summit vs. flank eruptions. The latter have been further subdivided into two categories: eruptions characterised by high effusion rates and short duration, and eruptions dominated by low effusion rate, long duration and larger volume of erupted lava. Circular zones around the summit area have been drawn for summit eruptions based on the maximum lava flow length; flank eruptions have been considered by taking into account the eruptive fracture elevation and combining them with lava flow lengths of 4 and 6 km. This work highlights that the greatest lava flow hazard at Etna is on the south and east sectors of the volcano. This should be properly considered in future land-use planning by local authorities.
    Description: Published
    Description: 407–443
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: JCR Journal
    Description: reserved
    Keywords: Mt. Etna ; effusive activity ; database ; lava flow length ; eruptive fractures ; vent elevation ; hazard zonation ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 8
    Publication Date: 2017-04-04
    Description: Volcanoes represent an important natural source of several trace elements to the atmosphere. For some species (e.g., As, Cd, Pb and Se) they may be the main natural source and thereby strongly influencing geochemical cycles from the local to the global scale. Mount Etna is one of the most actively degassing volcanoes in the world, and it is considered to be, on the long-term average, the major atmospheric point source of many environmental harmful compounds. Their emission occurs either through continuous passive degassing from open-conduit activity or through sporadic paroxysmal eruptive activity, in the form of gases, aerosols or particulate. To estimate the environmental impact of magma-derived trace metals and their depositions processes, rainwater and snow samples were collected at Mount Etna area. Five bulk collectors have been deployed at various altitudes on the upper flanks around the summit craters of the volcano; samples were collected every two week for a period of one year and analyzed for the main chemical-physical parameters (electric conductivity and pH) and for major and trace elements concentrations. Chemical analysis of rainwater clearly shows that the volcanic contribution is always prevailing in the sampling site closest to the summit crater (about 1.5 km). In the distal sites (5.5-10 km from the summit) and downwind of the summit craters, the volcanic contribution is also detectable but often overwhelmed by anthropogenic or other natural (seawater spray, geogenic dust) contributions. Volcanic contribution may derive from both dry and wet deposition of gases and aerosols from the volcanic plume, but sometimes also from leaching of freshly emitted volcanic ashes. In fact, in our background site (7.5 km in the upwind direction) volcanic contribution has been detected only following an ash deposition event. About 30 samples of fresh snow were collected in the upper part of the volcano, during the winters 2006 and 2007 to estimate deposition processes at high altitude during cold periods. Some of the samples were collected immediately after a major explosive event from the summit craters to understand the interaction between snow and fresh erupted ash. Sulphur, Chlorine and Fluorine, are the major elements that prevailingly characterize the volcanic contribution in atmospheric precipitation on Mount Etna, but high concentrations of many trace elements are also detected in the studied samples. In particular, bulk deposition samples display high concentration of Al, Fe, Ti, Cu, As, Rb, Pb, Tl, Cd, Cr, U and Ag, in the site most exposed to the volcanic emissions: median concentration values are about two orders of magnitude higher than those measured in our background site. Also in the snow samples the volcanic signature is clearly detectable and decreases with distance from the summit craters. Some of the analysed elements display very high enrichment values with respect to the average crust and, in the closest site to the summit craters, also deposition values higher than those measured in polluted urban or industrial sites.
    Description: Published
    Description: Vienna, Austria
    Description: 4.5. Degassamento naturale
    Description: open
    Keywords: Mt. Etna ; trace elements ; rainwater ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 03. Hydrosphere::03.03. Physical::03.03.01. Air/water/earth interactions ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Oral presentation
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  • 9
    Publication Date: 2017-04-04
    Description: Flank instability and collapse are observed at many volcanoes. Among these, Mt. Etna is characterized by the spreading of its eastern and southern flanks. The eastern spreading area is bordered to the north by the EW-trending Pernicana Fault System (PFS). During the 20022003 Etna eruption, ground fracturing along the PFS migrated eastward from the NE Rift, to as far as the 18 km distant coastline. The deformation consisted of dextral en-echelon segments, with sinistral and normal kinematics. Both of these components of displacement were one order of magnitude larger (~1 m) in the western, previously known, portion of the PFS with respect to the newly surveyed (~9 km long) eastern section (~0.1 m). This eastern section is located along a pre-existing, but previously unknown, fault, where displaced man-made structures give overall slip rates (11.9 cm/year), only slightly lower than those calculated for the western portion (1.42.3 cm/year). After an initial rapid motion during the first days of the 20022003 eruption, movement of the western portion of the PFS decreased dramatically, while parts of the eastern portion continued to move. These data suggest a model of spreading of the eastern flank of Etna along the PFS, characterized by eruptions along the NE Rift, instantaneous, short-lived, meter-scale displacements along the western PFS and more long-lived centimeter-scale displacements along the eastern PFS. The surface deformation then migrated southwards, reactivating, one after the other, the NNWSSE-trending Timpe and Trecastagni faults, with displacements of ~0.1 and ~0.04 m, respectively. These structures, along with the PFS, mark the boundaries of two adjacent blocks, moving at different times and rates. The new extent of the PFS and previous activity over its full length indicate that the sliding eastern flank extends well below the Ionian Sea. The clustering of seismic activity above 4 km b.s.l. during the eruption suggests a deep décollement for the moving mass. The collected data thus suggests a significant movement (volume 〉1,100 km3) of the eastern flank of Etna, both on-shore and off-shore.
    Description: Published
    Description: 417-430
    Description: partially_open
    Keywords: Volcano spreading ; Fracturing ; Mt. Etna ; Pernicana Fault System ; NE Rift ; 04. Solid Earth::04.04. Geology::04.04.09. Structural geology ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 10
    Publication Date: 2017-04-04
    Description: Hydrological and geochemical studies performed on Lake Specchio di Venere on Pantelleria island (Italy) indicate that this endorheic basin has been formed through upwelling of the water table, and that it is continuously fed by the thermal springs situated on its shores. The lake is periodically stratified both thermally and in salinity, albeit this stratification is rather unstable over time since meteorological events such as strong rain or wind can determine the mixing of its waters. Periodical analyses of the lake water chemistry show large variations of the salt content due to the yearly evaporation-rain dilution cycle. These processes are also responsible for the saline stratification during steady meteorological conditions. The mineralogical characterisation of the bottom sediments shows the almost exclusive presence of neoformation minerals, mainly carbonates, formed in response to the pH gradient between spring- (pH≈6) and lake-waters (pH≈9). Finally, the CO2 partial pressures in the lake water slightly exceeding the atmospheric one, are due to the large amounts of CO2 brought to the lake through the bubbling free gas phase of the thermal springs. Nevertheless the high pH value of the lake water, its small volume and its periodical mixing prevent dangerous built up of this gas.
    Description: Published
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: Pantelleria island ; volcanic lake ; gas hazard ; 03. Hydrosphere::03.02. Hydrology::03.02.02. Hydrological processes: interaction, transport, dynamics ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 11
    Publication Date: 2017-04-04
    Description: Improving the constraints on the atmospheric fate and depletion rates of acidic compounds persistently emitted by non-erupting (quiescent) volcanoes is important for quantitatively predicting the environmental impact of volcanic gas plumes. Here, we present new experimental data coupled with modelling studies to investigate the chemical processing of acidic volcanogenic species during tropospheric dispersion. Diffusive tube samplers were deployed at Mount Etna, a very active open-conduit basaltic volcano in eastern Sicily, and Vulcano Island, a closed-conduit quiescent volcano in the Aeolian Islands (northern Sicily). Sulphur dioxide (SO2), hydrogen sulphide (H2S), hydrogen chloride (HCl) and hydrogen fluoride (HF) concentrations in the volcanic plumes (typically several minutes to a few hours old) were repeatedly determined at distances from the summit vents ranging from 0.1 to ~10 km, and under different environmental conditions. At both volcanoes, acidic gas concentrations were found to decrease exponentially with distance from the summit vents (e.g., SO2 decreases from ~10,000 μg/m3 at 0.1 km from Etna’s vents down to ~7 _μg/m3 at ~10km distance), reflecting the atmospheric dilution of the plume within the acid gas-free background troposphere. Conversely, SO2/HCl, SO2/HF, and SO2/H2S ratios in the plume showed no systematic changes with plume aging, and fit source compositions within analytical error. Assuming that SO2 losses by reaction are small during short-range atmospheric transport within quiescent (ash-free) volcanic plumes, our observations suggest that, for these short transport distances, atmospheric reactions for H2S and halogens are also negligible. The one-dimensional model MISTRA was used to simulate quantitatively the evolution of halogen and sulphur compounds in the plume of Mt. Etna. Model predictions support the hypothesis of minor HCl chemical processing during plume transport, at least in cloud-free conditions. Larger variations in the modelled SO2/HCl ratios were predicted under cloudy conditions, due to heterogeneous chlorine cycling in the aerosol phase. The modelled evolution of the SO2/H2S ratios is found to be substantially dependent on whether or not the interactions of H2S with halogens are included in the model. In the former case, H2S is assumed to be oxidized in the atmosphere mainly by OH, which results in minor chemical loss for H2S during plume aging and produces a fair match between modelled and measured SO2/H2S ratios. In the latter case, fast oxidation of H2S by Cl leads to H2S chemical lifetimes in the early plume of a few seconds, and thus SO2 to H2S ratios that increase sharply during plume transport. This disagreement between modelled and observed plume compositions suggests that more in-detail kinetic investigations are required for a proper evaluation of H2S chemical processing in volcanic plumes.
    Description: Published
    Description: 1441-1450
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 4.5. Degassamento naturale
    Description: JCR Journal
    Description: open
    Keywords: Mt. Etna ; volcanic gas plumes ; tropospheric processing ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
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  • 12
    Publication Date: 2017-04-04
    Description: This study presents baseline data for future geochemical monitoring of the active Tacaná volcano–hydrothermal system (Mexico–Guatemala). Seven groups of thermal springs, related to a NW/SE-oriented fault scarp cutting the summit area (4,100m a.s.l.), discharge at the northwest foot of the volcano (1,500–2,000m a.s.l.); another one on the southern ends of Tacaná (La Calera). The near-neutral (pH from 5.8 to 6.9) thermal (T from 25.7°C to 63.0°C) HCO3–SO4 waters are thought to have formed by the absorption of a H2S/SO2–CO2-enriched steam into a Cl-rich geothermal aquifer, afterwards mixed by Na/HCO3-enriched meteoric waters originating from the higher elevations of the volcano as stated by the isotopic composition (δD and δ18O) of meteoric and spring waters. Boiling temperature fumaroles (89°C at~3,600m a.s.l. NW of the summit), formed after the May 1986 phreatic explosion, emit isotopically light vapour (δD and δ18O as low as −128 and −19.9‰, respectively) resulting from steam separation from the summit aquifer. Fumarolic as well as bubbling gases at five springs are CO2-dominated. The δ13CCO2 for all gases show typical magmatic values of −3.6 ± 1.3‰ vs V-PDB. The large range in 3He/4He ratios for bubbling, dissolved and fumarolic gases [from 1.3 to 6.9 atmospheric 3He/4He ratio (RA)] is ascribed to a different degree of near-surface boiling processes inside a heterogeneous aquifer at the contact between the volcanic edifice and the crystalline basement (4He source). Tacaná volcano offers a unique opportunity to give insight into shallow hydrothermal and deep magmatic processes affecting the CO2/3He ratio of gases: bubbling springs with lower gas/water ratios show higher 3He/4He ratios and consequently lower CO2/3He ratios (e.g. Zarco spring). Typical Central American CO2/3He and 3He/4He ratios are found for the fumarolic Agua Caliente and Zarco gases (3.1 ± 1.6 × 1010 and 6.0 ± 0.9 RA, respectively). The L/S (5.9 ± 0.5)and (L + S)/M ratios (9.2 ± 0.7) for the same gases are almost identical to the ones calculated for gases in El Salvador, suggesting an enhanced slab contribution as far as the northern extreme of the Central American Volcanic Arc,Tacana
    Description: In press
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 2.4. TTC - Laboratori di geochimica dei fluidi
    Description: JCR Journal
    Description: reserved
    Keywords: Tacaná volcano ; Fluid geochemistry ; Volcano–hydrothermal system ; Bubbling gases ; Fumaroles ; Isotopes ; Volcanic surveillance ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.02. Data dissemination::05.02.01. Geochemical data
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  • 13
    Publication Date: 2017-04-04
    Description: Kostrov's (1974) algorithm for seismic-strain tensor computations, in the version implemented by Wyss et al. (1992a) for error estimates, has been applied to shear-type earthquakes occurring beneath the Etna volcano during 1990-1996. Space-time variations of strain orientations and amplitudes have been examined jointly with ground-deformation and gravimetric data collected in the same period and reported in the literature. Taking also into account the information available from volcanological observations and structural geology, we propose a model assuming that hydraulic pressure by magma emplaced in nearly north-south vertical structures produces the E-W orientation of the maximum compressive strain found in the upper 10 km beneath the crater area. In contrast, regional tectonics deriving from the slow, north-south convergence between the African and European plates appear to play a dominant role in the generation of stress and strain fields at crustal depths deeper than 10 km below the volcano. According to our interpretation, the progressive ascent of magma through the upper crust prior to eruption produces the observed gravity changes, cone inflation and unusual seismic strain rate in the upper 10 km associated with a more sharply defined seismic deformation regime (i.e. very small confidence limits of the epsilon 1 orientation). In agreement with this model, deflation revealed by ground-deformation data during the course of the major 1991-1993 eruption was accompanied by a practically nil level of shallow seismicity.
    Description: Published
    Description: 318-330
    Description: JCR Journal
    Description: open
    Keywords: Mt. Etna ; Italy ; Earthquakes ; Seismic strain ; Stress inversion ; Volcanic processes ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
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  • 14
    Publication Date: 2017-04-04
    Description: Volcanic and geothermal areas are one of the major natural sources of H2S to the atmosphere. Its environmental impact is often the main cause of the opposition to the development of geothermal energy exploitation programs. In this paper we analyze the air concentrations and dispersion pattern of naturally emitted H2S at the geothermal area of Sousaki (Corinthia, Greece). Measurements, made with a network of passive samplers, evidence a rapid decrease of concentration values away from the emission points. The fact that the decrease is more pronounced in the summer with respect to the winter indicates that it is not only due to a dilution effect, but also to redox reactions favoured by higher temperatures and intense sunlight typical of the summer period.
    Description: Published
    Description: 1723-1728
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: Hydrogen sulphide ; Environmental impact of volcanic activity ; Gas hazard ; Passive samplers ; 01. Atmosphere::01.01. Atmosphere::01.01.03. Pollution ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 15
    Publication Date: 2017-04-04
    Description: Large variations of the CO2 flux through the soil were observed between November 2002 and January 2006 at Mt. Etna volcano. In many cases, the CO2 flux was strongly influenced by changes in air temperature and atmospheric pressure. A new filtering method was then developed to remove the atmospheric influences on soil CO2 flux and, at the same time, to highlight the variations strictly related to volcanic activity. Successively, the CO2 corrected data were quantitatively compared with the spectral amplitude of the volcanic tremor by cross correlation function, cross-wavelet spectrum and wavelet coherence. These analyses suggested that the soil CO2 flux variations preceded those of volcanic tremor by about 50 days. Given that volcanic tremor is linked to the shallow (a few kilometer) magma dynamics and soil CO2 flux related to the deeper (*12 km b.s.l.) magma dynamics, the “delayed similarity” between the CO2 flux and the volcanic tremor amplitude was used to assess the average speed in the magma uprising into the crust, as about 170–260 m per day. Finally, the large amount of CO2 released before the onset of the 2004–2005 eruption indicated a deep ingression of new magma, which might have triggered such an eruption.
    Description: In press
    Description: N/A or not JCR
    Description: reserved
    Keywords: Mt. Etna ; Soil CO2 flux ; Volcanic tremor ; Cross-wavelet spectrum ; Wavelet coherence ; Cross correlation function ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.02. Data dissemination::05.02.01. Geochemical data ; 05. General::05.02. Data dissemination::05.02.02. Seismological data
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  • 16
    Publication Date: 2017-04-04
    Description: The use of a hand-held thermal camera during the 2002–2003 Stromboli effusive eruption proved essential in tracking the development of flow field structures and in measuring related eruption parameters, such as the number of active vents and flow lengths. The steep underlying slope on which the flow field was emplaced resulted in a characteristic flow field morphology. This comprised a proximal shield, where flow stacking and inflation caused piling up of lava on the relatively flat ground of the vent zone, that fed a medial–distal lava flow field. This zone was characterized by the formation of lava tubes and tumuli forming a complex network of tumuli and flows linked by tubes. Most of the flow field was emplaced on extremely steep slopes and this had two effects. It caused flows to slide, as well as flow, and flow fronts to fail frequently, persistent flow front crumbling resulted in the production of an extensive debris field. Channel-fed flows were also characterized by development of excavated debris levees in this zone (Calvari et al. 2005). Collapse of lava flow fronts and inflation of the upper proximal lava shield made volume calculation very difficult. Comparison of the final field volume with that expecta by integrating the lava effusion rates through time suggests a loss of ~70% erupted lava by flow front crumbling and accumulation as debris flows below sea level. Derived relationships between effusion rate, flow length, and number of active vents showed systematic and correlated variations with time where spreading of volume between numerous flows caused an otherwise good correlation between effusion rate, flow length to break down. Observations collected during this eruption are useful in helping to understand lava flow processes on steep slopes, as well as in interpreting old lava–debris sequences found in other steep-sided volcanoes subject to effusive activity.
    Description: Published
    Description: JCR Journal
    Description: reserved
    Keywords: Lava flow field ; Morphology ; Tumuli ; Lava tubes ; Effusion rate ; Rheology ; Stromboli volcano ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.07. Instruments and techniques ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 17
    Publication Date: 2017-04-04
    Description: The catastrophic events that occurred in May 1998 in the area of Sarno (Southern Italy) highlight the destructive potential of debris flows, even when they are of relatively low magnitude. More than 130 people were killed and severe property damage took place when volcaniclastic debris flows triggered by heavy rainfall inundated various towns located in piedmont areas. This work investigates the suitability of LAHARZ, a GIS-assisted method for the automatic delineation of lahar inundation areas, for reproducing the May 1998 flows at Sarno. It was found that recalibration of the empirical relationship employed by LAHARZ is required in order to realistically hind-cast the inundation areas of considered events. The potential for further improvements in prediction outputs for this type of geomorphic setting is discussed, taking into account the observed lower mobility of these small volcaniclastic debris flows as compared to lahars of similar size.
    Description: Published
    Description: JCR Journal
    Description: reserved
    Keywords: Sarno ; LAHARZ ; Debris flows ; Lahars ; Debris flow modelling ; Hazard assessment ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 18
    Publication Date: 2017-04-04
    Description: An immersed boundary technique suitable for the solution of multiphase compressible equations of gas–particle flows of volcanic origin over complex 2D and 3D topographies has been developed and applied. This procedure combines and extends different existing methods designed for incompressible flows. Furthermore, the extension to compressible multiphase flows is achieved through a flux correction term in the mass continuity equations of the immersed cells that accounts for density variations in the partial volumes. The technique is computationally accurate and inexpensive, if compared to the use and implementation of the finite-volume technique on unstructured meshes. The first applications that we consider are the simulations of pyroclastic density currents generated by the collapse of a volcanic column in 2D axisymmetric geometry and by a dome explosion in 3D. Results show that the immersed boundary technique can significantly improve the description of the no-slip flow condition on an irregular topography even with relatively coarse meshes. Although the net effect of the present technique on the results is difficult to quantify in general terms, its adoption is recommended any time that cartesian grids are used to describe the large-scale dynamics of pyroclastic density currents over volcano topographies.
    Description: Published
    Description: 183-198
    Description: 3.6. Fisica del vulcanismo
    Description: JCR Journal
    Description: reserved
    Keywords: Pyroclastic density currents ; Compressible flows ; Cartesian grids ; Finite-volume method ; Immersed boundary method ; Numerical simulation ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 19
    Publication Date: 2017-04-04
    Description: The Campania Region (southern Italy) is characterized by the frequent occurrence of volcaniclastic debris flows that damage property and loss of life (more than 170 deaths between 1996 and 1999). Historical investigation allowed the identification of more than 500 events during the last four centuries; in particular, more than half of these occurred in the last 100 years, causing hundreds of deaths. The aim of this paper is to quantify debris-flow hazard potential in the Campania Region. To this end, we compared several elements such as the thickness distribution of pyroclastic fall deposits from the last 18 ka of the Vesuvius and Phlegrean Fields volcanoes, the slopes of relieves, and the historical record of volcaniclastic debris flows from A.D. 1500 to the present. Results show that flow occurrence is not only a function of the cumulative thickness of past pyroclastic fall deposits but also depends on the age of emplacement. Deposits younger than 10 ka (Holocene eruptions) apparently increase the risk of debris flows, while those older than 10 ka (Late Pleistocene eruptions) seem to play a less prominent role, which is probably due to different climatic conditions, and therefore different rates of erosion of pyroclastic falls between the Holocene and the Late Pleistocene. Based on the above considerations, we compiled a large-scale debris-flow hazard map of the study area in which five main hazard zones are identified: very low, low, moderate, high, and very high.
    Description: Published
    Description: 157-167
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: 5.4. TTC - Sistema Informativo Territoriale
    Description: JCR Journal
    Description: reserved
    Keywords: Debris flows ; Explosive eruptions ; Hazard mapping ; Vesuvius volcano ; Erosion ; Campania region ; Southern Italy ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 20
    Publication Date: 2017-04-04
    Description: The main purpose of this paper is to introduce a Bayesian event tree model for eruption forecasting (BET_EF). The model represents a flexible tool to provide probabilities of any specific event at which we are interested in, by merging all the relevant available information, such as theoretical models, a priori beliefs, monitoring measures, and any kind of past data. BET_EF is based on a Bayesian procedure and it relies on the fuzzy approach to manage monitoring data. The method deals with short- and long-term forecasting, therefore it can be useful in many practical aspects, as land use planning, and during volcanic emergencies. Finally, we provide the description of a free software package that provides a graphically supported computation of short- to long-term eruption forecasting, and a tutorial application to the recent MESIMEX exercise at Vesuvius.
    Description: Published
    Description: 623-632
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: JCR Journal
    Description: partially_open
    Keywords: eruption forecasting ; event tree ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 21
    Publication Date: 2017-04-04
    Description: Fluorine is one of the many environmental harmful elements released by volcanic activity. The content of total, oxalate extractable and water extractable fluorine was determined in 96 topsoils of three active volcanic systems of southern Italy (Mt. Etna, Stromboli and Vulcano). Total fluorine content (FTOT) ranges from 112 to 7430 mg kg-1, F extracted with oxalate (FOX) ranges from 16 to 2320 mg kg-1 (2 – 93 % of FTOT) and F extracted with distilled water (FH2O) ranges from 1.7 to 159 mg kg-1 (0.2 – 40 % of FTOT). Fluorine in the sampled topsoils derives both from the weathering of volcanic rocks and ashes and from enhanced deposition due to volcanic gas emissions either from open-conduit passive degassing (Mt. Etna and Stromboli) or from a fumarolic field (Vulcano). Fluorine accumulation in the studied soils does generally not present particular environmental issues except for a few anomalous sites at Vulcano where measured contents could be dangerous both for vegetation and for grazing animals.
    Description: Published
    Description: 413-423
    Description: 4.5. Degassamento naturale
    Description: JCR Journal
    Description: reserved
    Keywords: soil fluorine ; oxalate extractable F ; water extractable F ; environmental impact of volcanic F ; Sicily ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
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  • 22
    Publication Date: 2017-04-04
    Description: We consider the process of slow extrusion of very viscous magma that forms lava domes. Dome-building eruptions are commonly associated with hazardous phenomena, in- cluding pyroclastic flows generated by dome collapses, explosive eruptions and volcanic blasts. These eruptions commonly display fairly regular alternations between pe- riods of high and low or no activity with time scales from hours to years. Usually hazardous phenomena are asso- ciated with periods of high magma discharge rate, thus, understanding the causes of pulsatory activity during ex- trusive eruptions is an important step towards forecasting volcanic behavior, especially the transition to explosive ac- tivity when magma discharge rate increases by a few orders of magnitude. In recent years the risks have increased be- cause the population density in the vicinity of many active volcanoes has increased.
    Description: Published
    Description: 3.6. Fisica del vulcanismo
    Description: open
    Keywords: Volcanic Eruptions ; Cyclicity ; During Lava ; 04. Solid Earth::04.01. Earth Interior::04.01.99. General or miscellaneous ; 04. Solid Earth::04.08. Volcanology::04.08.04. Thermodynamics ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 23
    Publication Date: 2017-04-04
    Description: Following the 2001 and 2002–2003 flank eruptions, activity resumed at Mt. Etna on 7 September 2004 and lasted for about 6 months. This paper presents new petrographic, major and trace element, and Sr–Nd isotope data from sequential samples collected during the entire 2004–2005 eruption. The progressive change of lava composition allowed defining three phases that correspond to different processes controlling magma dynamics inside the central volcano conduits. The compositional variability of products erupted up to 24 September is well reproduced by a fractional crystallization model that involves magma already stored at shallow depth since the 2002–2003 eruption. The progressive mixing of this magma with a distinct new one rising within the central conduits is clearly revealed by the composition of the products erupted from 24 September to 15 October. After 15 October, the contribution from the new magma gradually becomes predominant, and the efficiency of the mixing process ensures the emission of homogeneous products up to the end of the eruption. Our results give insights into the complex conditions of magma storage and evolution in the shallow plumbing system of Mt. Etna during a flank eruption. Furthermore, they confirm that the 2004–2005 activity at Etna was triggered by regional movements of the eastern flank of the volcano. They caused the opening of a complex fracture zone extending ESE which drained a magma stored at shallow depth since the 2002–2003 eruption. This process favored the ascent of a different magma in the central conduits, which began to be erupted on 24 September without any significant change in eruptive style, deformation, and seismicity until the end of eruption.
    Description: Published
    Description: 781–793
    Description: 2.3. TTC - Laboratori di chimica e fisica delle rocce
    Description: JCR Journal
    Description: reserved
    Keywords: Geochemistry ; Isotopic compositions ; Magma feeding system ; Magma mixing ; Mt. Etna ; 04. Solid Earth::04.08. Volcanology::04.08.03. Magmas ; 04. Solid Earth::04.08. Volcanology::04.08.05. Volcanic rocks
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  • 24
    Publication Date: 2022-02-16
    Description: The role of mud volcanoes (MVs) as a source of methane(CH4) flux to the atmosphere and the ocean has been increasingly recognised in the last several years (Milkov 2000; Dimitrov 2002, 2003; Etiope and Klusman 2002; Kopf 2002, 2003; Milkov et al. 2003; Etiope and Milkov 2004). In one of the most recent papers, Kopf (2003) claims to report a reliable estimate of the global CH4 emission from MVs. However, the significance and usefulness of the estimate presented by Kopf (2003) are rather poor. The used dataset is smaller than in previous studies (although the author makes a reverse claim), and some previously published works are misquoted and misinterpreted. Numerous arithmetic mistakes made during simple calculations and data manipulations lead to confusing results and conclusions. In this comment, we highlight some of the most significant problems with the estimates published by Kopf (2003).
    Description: Published
    Description: 490-492
    Description: 4.5. Degassamento naturale
    Description: JCR Journal
    Description: reserved
    Keywords: Methane ; mud volcanoes ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
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  • 25
    Electronic Resource
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    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
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  • 26
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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  • 27
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    Entomologia experimentalis et applicata 74 (1995), S. 115-119 
    ISSN: 1570-7458
    Keywords: wheat ; aphids ; hydroxamic acids ; DIMBOA ; DIMBOA-glucoside ; EPG ; electrical penetration graph ; feeding deterrents ; antixenosis ; plant resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Feeding behaviour of five species of cereal aphids in wheat seedlings differing in hydroxamic acid (Hx) levels, was monitored via electrical penetration graphs (EPG). Aphid species could be grouped as sensitive to the feeding deterrent effect of Hx in the seedlings (Rhopalosiphum padi, Schizaphis graminum, Sitobion avenae, andMetopolophium dirhodum) or insensitive to them (Rhopalosiphum maidis). However, when feeding behaviour was studied in artificial diets containing Hx, all species were equally sensitive to Hx. The behavour ofR. maidis was further compared with that ofR. padi through detailed EPG analysis. It was found that the insensitivity ofR. maidis to Hx in seedlings may be due to a feeding strategy avoiding contact with the compounds by decreasing the number of cellular punctures in live tissues other than sieve elements during its way to the phloem.
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  • 28
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    Entomologia experimentalis et applicata 74 (1995), S. 283-294 
    ISSN: 1570-7458
    Keywords: hypersensitivity ; Hessian fly ; plant resistance ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Hessian flyMayetiola destructor (Say) larvae are able to obtain food from their host plant without inflicting mechanical damage to the plant surface, apparently by secreting substances which elicit release of nutrients from plant cells surrounding the feeding site. Cells of fully susceptible plants retain their normal appearances, while in resistant plants extensive areas of cellular collapse occur. These responses indicate that hypersensitivity is the basis of wheat's resistance to the Hessian fly. The fly's feeding mechanism more closely resembles that of a pathogen than of a phytophagous insect; correspondingly, both the genetic relationship and resistance mechanism of the host plant to the parasite are of the sorts commonly associated with bacterial and fungal pathogens.
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  • 29
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    Entomologia experimentalis et applicata 93 (1999), S. 227-230 
    ISSN: 1570-7458
    Keywords: Rhopalosiphum padi ; cereal aphids ; wheat ; induced responses ; feeding site
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 30
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    Entomologia experimentalis et applicata 92 (1999), S. 157-164 
    ISSN: 1570-7458
    Keywords: plant resistance ; antibiosis ; tolerance ; antixenosis ; Russian wheat aphid ; wheat ; Homoptera ; Aphididae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Russian wheat aphid, Diuraphis noxia (Mordvilko), is one of the most important aphid pests of wheat, Triticum aestivum L., worldwide. Among the various pest management options, plant resistance is an economical management tactic to control D. noxia in cereal crops such as wheat. Researchers have identified D. noxia resistant germplasm and it has been incorporated into wheat. This study compared D. noxia resistance between the ‘Betta’ wheat isolines Betta-Dn1, Betta-Dn2, and Betta-Dn5 and their corresponding donor gene plant introduction (PI) lines PI 137739 (Dn1), PI 262660 (Dn2), and PI 294994 (Dn5). Although the Betta isolines and PI lines showed D. noxia resistance when compared with Betta wheat, the degree of resistance in the isolines to D. noxia was different from their corresponding PI donors. Aphid number, aphid fecundity, and biomass per aphid were not different between Betta-Dn1 and PI 137739 or Betta-Dn2 and PI 262660; however, the same parameters were significantly lower on PI 294994 compared with Betta-Dn5. This indicated that aphid resistance in PI 137739 and PI 262660 was probably governed by a single dominant gene, while the resistance in PI 294994 was controlled by more than one gene. Additionally, plant biomass reduction was aphid density dependent, which suggested that use of appropriate aphid infestation level is important when using plant biomass reduction as an indicator of resistance. Plant resistance categorization showed that there was no detectable difference in antixenosis among the seven lines evaluated. However, the higher aphid fecundity observed on PI 262660 compared with PI 137739 and PI 294994, in addition to no significant differences among the three PIs in plant biomass reduction, suggested PI 262660 was a tolerant line, while PI 137739 and PI 294994 were antibiotic lines. Plant tolerance could not be elucidated among the three Betta isolines using aphid fecundity and plant biomass reduction as indicators.
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  • 31
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    Entomologia experimentalis et applicata 89 (1998), S. 111-118 
    ISSN: 1570-7458
    Keywords: leaf surface wax ; probing behavior ; nymphoposition ; Russian wheat aphid ; wheat ; barley ; oat ; Homoptera ; Aphididae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effect of cereal leaf surface wax on Diuraphis noxia (Mordvilko), the Russian wheat aphid, probing behavior and nymphoposition was evaluated. Ultrastructure of leaf epicuticular wax from wheat (Triticum aestivum L.) c.v. ‘Arapahoe’ and ‘Halt’ was different from barley (Hordeum vulgare L.) c.v. ‘Morex’, and oat (Avena sativa L.) c.v. ‘Border’. Both wheat cultivars had similar rod-shaped epicuticular wax, while barley and oat plants had flakes. The chemical composition comparison of gas chromatograms also indicated that the extract of the two wheat cultivars had similar pattern of peaks, while the barley and oat leaves had similar peaks. Cereal variety significantly affected aphid probing behavior (P 〈 0.05), but wax removal using ethyl ether swab did not (P 〈 0.05). Aphids initiated significantly more probes on Border oat leaves than on Morex barley irrespective of wax removal, although total probing duration per aphid was not significantly different among the four cereals examined. Accumulative salivation duration per aphid on oat leaves with wax was significantly longer than other cereal leaves with wax, while accumulative ingestion duration per aphid on Arapahoe wheat and Morex barley was significantly longer than on oat. Nymphoposition of D. noxia on cereal leaves maintained on the benzimidazole-agar medium showed that aphids produced a greater number of nymphs on Morex barley and less on Border oat leaves, although wax removal did not affect aphid nymphoposition. Removal of leaf epicuticular waxes from the 4 cereal genotypes using ethyl ether swab indicated that the influence of wax on plant resistance to D. noxia probing and reproduction was limited. Morex barley was the most favorable, while Border oat was the least favorable cereal host of D. noxia.
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  • 32
    ISSN: 1570-7458
    Keywords: sieve element ; salivation ; aphid ; plant resistance ; wheat ; Sitobion fragariae ; Triticum aestivum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Extended sieve element salivation (E1 waveform in the electrical penetration graph) is a characteristic activity during early sieve element punctures, particularly in resistant plants. In order to explore a chemically-mediated mechanism of resistance associated with sieve element salivation, we compared the pattern of feeding behaviour of the aphid, Sitobion fragariae (Walker), on two cultivars of the wheat Triticum aestivum L., with different concentrations of hydroxamic acids (Hx). During 24 h of electronic monitoring, aphids dedicated over 50% of the total time to phloem ingestion from the sieve elements. Total time allocated to E1 in the experiment, time to first E1 within the experiment, time allocated to E1 before a sustained phloem ingestion (E2) and the contribution of sieve element salivation to the phloem phase (E1/[E1+E2]) were significantly higher in the high-Hx cultivar. The increased salivation in plants with higher contents of Hx suggests the existence, at least in this system, of a chemically-mediated sieve element constraint.
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  • 33
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    Calcified tissue international 12 (1973), S. 313-321 
    ISSN: 1432-0827
    Keywords: Cathepsin D ; Extracellular ; Ossification ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé De la cathepsine D extracellulaire d'origine principalement ostéoblastique a été démontrée par immunohistochimie dans le cartilage en voide de calcification de cultures d'os des membres d'embryons de poulet. L'intérêt de ce fait pour l'ossification est discuté.
    Abstract: Zusammenfassung Es wurde mit einer immunohistochemischen Methode gezeigt, daß extrazelluläres Kathepsin D, welches hauptsächlich aus Osteoblasten gewonnen wurde, Knorpel von kultivierten Knochen von Kükenembryonen mineralisiert. Die Bedeutung dieser Feststellung für den Mechanismus der Knochenbildung wird diskutiert.
    Notes: Abstract Extracellular cathepsin D derived mainly from osteoblasts has been demonstrated immunohistochemically in ossifying cartilage of cultured embryonic chick limb bones. The relevance of this observation to the mechanism of ossification is discussed.
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  • 34
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    Plant molecular biology reporter 17 (1999), S. 323-331 
    ISSN: 1572-9818
    Keywords: Agrobacterium ; modular vector ; transformation ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Wheat (cv Chinese Spring) tissues were transformed using Agrobacterium tumefasciens and a new plasmid modular vector, pMVTBP. We constructed pMVTBP with unique restriction sites connecting (1) the CaMV 35S promoter, (2) a Kozak sequence, (3) the FLAG epitope, (4) the (His)6 epitope, (5) a coding region (for wheat TATA Binding Protein, wTBP) and (6) the CaMV 35S 3′UTR. This vector thus allows easy exchange of different regulatory or coding sequences. Explants of either germinating mature seeds, or immature embryos, were induced to callus for up to two weeks, treated with virulence-induced bacteria for one hour, then regenerated into plantlets. Transient expression of a GUS reporter gene, assayed at about one week, occurred in 10–12% of calluses. Expression of the FLAG-tagged wTBP was also detected, by immunostaining. Stable expression, by selective growth on geneticin, and by GUS expression at about six weeks, occurred in 1–2% of calluses, quite comparable to that achieved by other methods.
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  • 35
    ISSN: 1573-0832
    Keywords: deoxynivalenol ; enzyme immunoassay ; feed ; maize ; mycotoxins ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Samples of wheat (n = 25) and maize (n = 30) for animal consumption, collected in 1997 after harvest from western Romania, were analyzed by enzyme immunoassays for mycotoxin contamination. Toxins analyses included deoxynivalenol (DON), 3-acetylDON, 15- acetylDON, fusarenone X (FX), T-2 Toxin (T-2), diacetoxyscirpenol (DAS), zearalenone (ZEA), fumonisin B1 (FB1), aflatoxin B1 (AFB1), ochratoxin A (OA), and citrinin (CT). DON and acetylDONs were the major contaminants in wheat (100%) and maize (46%). Median values for DON, 3-acetylDON, and 15-acetylDON were 880 μg kg-1, 66 μg kg- 1, and 150 μg kg-1 in wheat, and 890 μg kg-1, 180 μg kg-1, and 620 μg kg- 1 in maize, respectively. Additionally, 3,15-diacetylDON was detected in some samples by HPLC-EIA analysis. All samples were negative for FX (〈150 μg kg-1). T-2 was found in wheat (n = 6) and maize (n = 1) at levels between 13 and 63 μg kg- 1. DAS (2.6 μg kg-1) was found in one maize sample. ZEA occurred in all wheat and in four maize samples, median values were 10 μg kg-1 and 250 μg kg-1, respectively. One maize sample contained FB1 (140 μg kg-1). All samples were AFB1-negative (〈4 μg kg-1). OA was found in one wheat sample (37 μg kg- 1), CT was found in one maize sample (580 μg kg- 1). This first reported natural occurrence of a range of mycotoxins in Romanian feeding stuff shows that DON and acetyl DONs may be present at levels which may affect animal production.
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  • 36
    ISSN: 1573-0832
    Keywords: ELISA ; Endodermis ; H. annosum ; Immunocytochemistry ; Root rot ; Vascular tissues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Vascular disintegration mainly of medulla rays of spruce roots is of major significance in root rot disease of spruce caused byH. annosum. Using seedling roots as an experimental model, the possible routes and initial host reactions preceding invasion of vascular tissues was investigated. Transmission electron microscopy showed that penetration through the endodermis was an obvious route but not without host resistance. Using antibodies againstH. annosum hyphal materials, some labelling of vascular tissues remote from sites of fungal colonization suggest the release of fungal secretory products partly active in tissue disintegration. Similarly, intense labelling was also observed in severely colonized host tissues at late stages of infection. Strong labelling recorded at 3 d p.i. mainly on fungal hyphae and scant gold particles on invaded host tissues could imply that induction of host antifungal metabolites may have been a late event. A correlation was found between total antigenic material in root homogenates measured by ELISA, density of tissue labelling by immunocytochemistry and severity of disease symptoms. The importance of this in relation to diagnosis of biotic root rot diseases in the field is discussed.
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  • 37
    ISSN: 1573-0832
    Keywords: Fusarium ; mycotoxins ; occurrence ; trichothecenes ; wheat ; zearalenone ; deoxynivalenol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Wheat for human consumption (140 samples) was collected after harvest from all regions of Bulgaria. The 1995 crop year was characterized by heavy rainfall in the spring and summer months. The internal mycoflora of wheat samples was dominated by Fusarium spp. and Alternaria spp., and storage fungi were rarely present. The samples were analysed for contamination with Fusarium mycotoxins deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-AcDON), 15-acetyldeoxynivalenol (15-AcDON), T-2 Toxin (T-2), diacetoxyscirpenol (DAS), and zearalenone (ZEA), using enzyme immunoassay methods. DON and ZEA were the predominant toxins, with a contamination frequency of 67% and 69%, respectively. The average levels of these toxins in positive samples were 180 μg/kg (DON) and 17 μg/kg (ZEA), maximum concentrations were 1800 μg kg−1 and 120 μg kg−1, respectively. Acetyl derivatives of DON, namely 3-AcDON and 15-AcDON, were found in 2.1 % and 0.7% of the samples, at at maximum level of about 100 μg kg−1. Only one sample was positive for T-2 (55 μg/kg), DAS was not detected. This is the first report about the natural occurrence of a range of Fusarium mycotoxins in wheat for human consumption in Bulgaria.
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  • 38
    ISSN: 1573-0867
    Keywords: 15N ; non-nod beans ; quantification of N2 fixation ; reference crops ; simulation technique ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A technique for the application of the15N isotope dilution technique for the quantification of plant associated biological nitrogen fixation (BNF) was tested and applied to quantify the BNF contribution to two genotypes ofPhaseolus vulgaris. The technique makes use of sequential measurements of the15N enrichment of soil mineral N, and the uptake of labelled N by the “N2-fixing” plant, to simulate its uptake of soil N (the “soil to plant simulation” technique). The test was made with two non-N2-fixing crops (non-nodulating beans and wheat) and two bean genotypes (PR 923450 and Puebla 152), at two levels of N fertilizer addition (10 and 40 kg N ha−1), to compare the actual N uptake with that simulated from the soil and crop15N data. The simulation of the soil N uptake by the non-nod bean crop using this “soil to plant simulation” technique underestimated by 20 to 30% the true N uptake, suggesting that the mineral N extracted from soil samples taken from the 0–15cm layer had a higher15N enrichment than that N sampled by the roots of this crop. In the case of the wheat crop the simulation resulted in a much greater underestimation of actual N uptake. In general the results using this technique suggested that BNF inputs to the bean cultivars was higher than would be expected from the nodulation and acetylene reduction data, except for the early PR beans in the 40 kg N ha−1 treatment. In this case the total N and simulated soil N accumulation were well matched suggesting no BNF inputs. An allied technique (the “plant to plant simulation technique”) was proposed where the15N enrichrnent of soil mineral N was simulated from the data for total N and labelled N accumulation taken from sequential harvests of either of the non-N2 -fixing control crops. This was then utilized in combination with the labelled N uptake data of the other crop to simulate its soil N uptake. However, the results using either technique indicated that the wheat and non-nod or nodulating beans exploited pools of N in the soil with completely different15N enrichments probably due to differences in exploitation of the soil N with depth.
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  • 39
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    Nutrient cycling in agroecosystems 45 (1995), S. 209-215 
    ISSN: 1573-0867
    Keywords: climate ; fertilizer recovery ; 15N fertilizer ; precipitation-evaporation quotient ; soil ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Data was assembled from experiments on the fate of15N-labelled fertilizer applied to wheat (Triticum spp.) grown in different parts of the world. These data were then ranked according to the annual precipitation-evaporation quotient for each experimental location calculated from the average long-term values of precipitation and potential evaporation. Percentage recovery of15N fertilizer in crop and soil varied with location in accordance with the precipitation-evaporation quotient. In humid environments more15N fertilizer was recovered in the crop than in the soil, while in dry environments more15N fertilizer was recovered in the soil than in the crop. Irrespective of climatic differences between locations 20% (on average) of the15N fertilizer applied to wheat crops was unaccounted for at harvest. Most of the15N fertilizer remaining in the soil was found in the 0–30 cm layer. The most likely explanation of these differences is that wheat grown in dry environments has a greater root:shoot ratio than wheat grown in humid environments and, further, that the residue of dryland crops have higher C/N ratios. Both factors could contribute to the greater recovery of15N fertilizer in the soil in dry environments than in humid ones.
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  • 40
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    Nutrient cycling in agroecosystems 46 (1996), S. 225-234 
    ISSN: 1573-0867
    Keywords: long-term experiment ; maize ; wheat ; fertilizers ; farm yard manure ; weedicide application ; yield sustainability ; zinc deficiency ; nutrient uptake ; cropping sequence ; organic carbon build-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Long-term field experiments play an important role in understanding the complex interactions of plants, soils, climate and management and their effects on sustainable crop production. A long-term fertilizer experiment with maize-wheat-cowpea (fodder) is in progress since 1971 at Punjab Agricultural University farm Ludhiana, India. The experimental result for the first 21 years showed that application of N alone or in combination with P did not produce as much maize and wheat grains as the application of N, P and K together. Eight years after the start of the experiment, the optimal levels of N, P and K application (100% NPK) were unable to sustain the similar (maize) yield level as before because of Zn deficiency. Whereas in FYM amended plots the Zn deficiency did not appear and the higher crop yields could be sustained. The chemical control of weeds could not sustain the maize productivity at the same level as the manual removal of weeds. It was concluded that the high level of crop production can be sustained with the application of N, P and K under intensive cropping system provided deficiency of any of the micronutrient does not crop up. The deficiency of Zn is most likely to occur in semi-arid light textured alluvial soils under intensive cropping without the addition of farm yard manure/organic manures. In maize based cropping systems, manual control of weeds may be preferred to the chemical one. Addition of FYM in conjunction with 100% NPK is most beneficial both from bio-physical and economic point of view.
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  • 41
    ISSN: 1573-0867
    Keywords: millet ; sorghum ; rice ; maize ; wheat ; nutrient harvest index ; post-anthesis nutrient uptake ; recovery fraction ; simulation modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In land use plans, fertilizer recommendations are indispensable to avoid soil nutrient depletion or soil water pollution. Nutrient relations of five cereals have been evaluated on the basis of a literature review with the aim of arriving at such fertilizer recommendations at regional level. Nutrients considered were nitrogen, phosphorus and potassium for millet, sorghum, maize, rice and wheat. The relevant nutrient relations are fertilizer nutrient application to nutrient uptake, and nutrient uptake to crop yield. In addition, post-anthesis nutrient uptake is considered. Subsequently, obtained results are used in simulation modelling exercises to calculate the time required to attain an equilibrium nutrient balance and to investigate the effect of erosion control and straw recycling. Although fertilizer requirements could be assessed for each of the five cereals, monitoring of nutrient supply from natural sources remains necessary. Moreover, research on fertilizer use should focus on improvement of fertilizer recoveries and multiperiod models for both N and P uptakes by crops to allow quantitative land use planning where the time scale is included.
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  • 42
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    Nutrient cycling in agroecosystems 44 (1995), S. 217-223 
    ISSN: 1573-0867
    Keywords: foliar fertilizer ; nitrate ; potassium ; urea ; wheat ; yield
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Winter wheat crops were grown with ostensibly adequate supplies of all soil nutrients in 1990 and 1991 with the aim of testing if late foliar supplements of K and N, applied at key development stages, could improve grain yield and grain N content. Foliar sprays of KNO3 solution, supplying up to 40 kg K ha−1 in total, at flag leaf unfolded, inflorescence completed and the watery-ripe stage of grain filling, had no effect on yield, yield components or grain N. Urea, supplying 40 kg N ha−1 at flag leaf unfolded, had no effects on grain yield and grain N in 1990, but in 1991 grain N was increased by 0.14% whilst yield was reduced by up to 0.6 t ha−1. Urea scorched flag leaf tips in both years. In 1990, the spring was very dry and foliar supplements might have been expected to have had an effect, but on this highly fertile soil all crop K and N requirements were met from the soil.
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  • 43
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    Nutrient cycling in agroecosystems 53 (1999), S. 139-146 
    ISSN: 1573-0867
    Keywords: critical levels of Mn ; soil extractants ; Mn-deficiency ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Seven chemical extractants were tested for their relative performance to predict the response of wheat to Mn application in coarse textured alkaline soils of semi-arid region. Five out of the seven extractants were found to be promising for the estimation of critical level of available Mn in these soils, as the amount of Mn extracted by these extractants was positively and significantly correlated with relative grain yield as well as Mn uptake. The critical deficiency level of soil available Mn with 0.005 M DTPA, 0.02% hydroquinone, 0.02 N sodium pyrophosphate, 0.1N H3PO4 and 0.05N HCl+0.025N H2SO4 was 3.1, 13.8, 23.5, 5.3 and 17.8 mg kg-1 soil, respectively. The 1N ammonium acetate and 0.01M CaCl2 were found to be unsuitable extractants for these soils. Further field trials at eight locations with varying levels of Mn deficiency showed successive increase in the grain yield of wheat with foliar Mn application, emphasizing the need for Mn fertilization when wheat is grown on Mn deficient soils.
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  • 44
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    Nutrient cycling in agroecosystems 45 (1995), S. 163-167 
    ISSN: 1573-0867
    Keywords: Basal dressing ; Se-enriched fertilizers ; Se-uptake ; soil texture ; top-dressing ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A multisite field experiment was conducted to study the effect of topdressed Se-enriched Ca(NO3)2 (CN) and basal applied NPK on the selenium (Se) concentration in spring wheat (Triticum aestivum L.). Selenium was applied either through CN (at the rates of 0, 6.45, and 12.91 g Se ha−1) or NPK (5.83 g Se ha−1). Selenium concentration in wheat grains increased consistently with increasing rate of Se-enriched CN or NPK. However, the superiority of Se-enriched CN over NPK in raising the Se concentration in wheat grain depended on location and growth conditions. At the same rate both methods of Se-application were found to be equally effective in raising the Se concentration of wheat grains. The Se concentration of grain was generally higher in the light textured soils than in the medium to heavy textured soils. Without Se application, the Se-concentration in wheat grain was about 16µg kg−1 which is regarded insufficient to meet the Se requirement for Se in animal and human. Calcium nitrate enriched with 25 mg Se kg−1 (6.45 g Se ha−1) increased the Se concentration in wheat grain to a desired level.
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  • 45
    ISSN: 1572-9699
    Keywords: bioluminescence ; Pseudomonas ; root colonization ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The bioluminescently marked Pseudomonas fluorescens strain 5RL, has been used previously to follow colonisation of soy bean roots (De Weger et al. [1991] Appl. Environ. Microbiol. 57:36-41). In the present paper the method has been further developed and optimized for wheat roots and it is used to get a quick overview of the colonisation patterns of many different root systems at the same time. Colonisation was followed on wheat plants grown in our gnotobiotic sand system (Simons et al., 1996. Mol Plant Microbe Interact 9: 600–607) and the following results were obtained. (i) A spatio-temporal analysis of the colonisation of wheat roots showed that 4 days after planting the highest bacterial activity was observed at the upper part of the root. After 6 days the high bacterial activity at the upper part was further increased, whereas spot-like activities were observed on the lower root parts, possibly due to micro-colonies. (ii) Bacterial mutations causing lack of motility or auxotrophy for amino acids resulted in impaired colonisation of the lower root parts, indicating that motility and prototrophy for the involved amino acid(s) are important factors for wheat root colonisation by strain 5RL. (iii) Coinoculation of strain 5RL with other wild type Pseudomonas strains on the root influenced the colonisation pattern observed for strain 5RL. Colonisation was not visually affected when the competing strain was a poor root coloniser, but was severely reduced when the competing strain was a good root coloniser. The results show that the spatio-temporal colonisation of wheat root by P. fluorescens strain 5RL and derivatives is similar to that of strain WCS365 on tomato. The advantage of the use of lux-marked strains is that the results are obtained much quicker than when conventional methods are used and that the result is supplied as an image of the colonisation pattern of many different roots.
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  • 46
    ISSN: 1572-9761
    Keywords: Coccinellidae ; Aphididae ; wheat ; spatial scale ; species diversity ; numerical response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The influence of prey density, within-field vegetation, and the composition and patchiness of the surrounding landscape on the abundance of insect predators of cereal aphids was studied in wheat fields in eastern South Dakota, USA. Cereal aphids, aphid predators, and within-field vegetation were sampled in 104 fields over a three year period (1988–1990). The composition and patchiness of the landscape surrounding each field were determined from high altitude aerial photographs. Five landscape variables, aggregated at three spatial scales ranging from 2.6 km2 to 581 km2, were measured from aerial photographs. Regression models incorporating within-field and landscape variables accounted for 27–49% of the variance in aphid predator abundance in wheat fields. Aphid predator species richness and species diversity were also related to within-field and landscape variables. Some predators were strongly influenced by variability in the composition and patchiness of the landscape surrounding a field at a particular spatial scale while others responded to variability at all scales. Overall, predator abundance, species richness, and species diversity increased with increasing vegetational diversity in wheat fields and with increasing amounts of non-cultivated lands and increasing patchiness in the surrounding landscape.
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  • 47
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    Integrated pest management reviews 4 (1999), S. 127-143 
    ISSN: 1572-9745
    Keywords: wheat ; stored-grain ; integrated pest management ; aeration ; biological control ; grain sampling ; insect monitoring ; modeling ; area-wide IPM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Management of stored-grain insect pests by farmers or elevator managers should be based upon a knowledge of the grain storage environment and the ecology of insect pests. Grain storage facilities and practices, geographical location, government policies, and marketing demands for grain quality are discussed as factors influencing stored-grain insect pest management decisions in the United States. Typical practices include a small number of grain samples designed to provide grain quality information for segregation, blending and marketing. This low sampling rate results in subjective evaluation and inconsistent penalties for insect-related quality factors. Information on the efficacy of insect pest management practices in the United States, mainly for farm-stored wheat, is discussed, and stored-grain integrated pest management (IPM) is compared to field-crop IPM. The transition from traditional stored-grain insect pest control to IPM will require greater emphasis on sampling to estimate insect densities, the development of sound economic thresholds and decision-making strategies, more selective use of pesticides, and greater use of nonchemical methods such as aeration. New developments in insect monitoring, predictive computer models, grain cooling by aeration, biological control, and fumigation are reviewed, their potential for improving insect pest management is discussed, and future research needs are examined.
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  • 48
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    Trees 13 (1999), S. 138-151 
    ISSN: 0931-1890
    Keywords: Key words Cytoskeleton ; Immunocytochemistry ; Model systems ; Populus ; Secondary vascular system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract  Trees represent a, probably the, major component of the biosphere and have a unique place in the history of Mankind. One of their most fascinating features is the process of secondary growth which is effected principally by the secondary vascular system, the developmental continuum of secondary phloem, vascular cambium, and secondary xylem. However, for too long assumptions about the developmental biology of trees have had to be based upon studies of primary growth systems within annual, herbaceous species because study of the secondary vascular system had been largely ignored. Even when attempts are made to understand some of the most fundamental features of the secondary vascular system, such as xylogenesis, the current model system, isolated Zinnia mesophyll cells, is not entirely appropriate to the situation in the intact tree. Some deficiencies of the Zinnia system are discussed, and the advantages of the genus Populus as a model for study of the hardwood secondary vascular system are considered. Some of the new approaches which are poised to lead to significant advances in our knowledge of the cell bio-logy of the secondary vascular system of trees – spe-cifically of the cell wall, the plasmalemma, and the cytoskeleton – are discussed. The value of one of these new techniques – immunocytochemistry – is demonstrated by a consideration of recent work on the role of the cytoskeleton in the hardwood secondary vascular system.
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  • 49
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    Histochemistry and cell biology 106 (1996), S. 9-17 
    ISSN: 1432-119X
    Keywords: Silver enhancement ; Immunogold-silver staining ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The immunogold silver staining method (IGSS) is widely used as a sensitive and specific immunohistochemical visualisation technique. IGSS involves the specific deposition of metallic silver at the site of immunogold labelling and provides a means of visualisation at low magnification by light or electron microscopy. Silver developers for IGSS rapidly deposit metallic silver only at the site of heavy metals, including gold and silver, because of their catalytic activity. The developing solution contains the silver ions and reducing agent necessary for this reaction. Using different silver salts as ion donors and by selecting an appropriate temperature and pH, visible amounts of silver can be deposited in a few minutes at the site of colloidal gold labelling while little non-specific background deposition occurs. Inclusion of protective colloids in the solution can also be used to control the reaction. Although studies of the chemical basis of silver deposition around unlabelled colloidal gold date back to 1939, immunogold enhancement by silver was established in 1983. The IGSS method evolved from the combination of disparate photographic, histochemical and immunogold techniques which have been effectively combined and optimised over the last 10 years to provide a visualisation system which is well suited to many immunohistochemical studies.
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    Histochemistry and cell biology 106 (1996), S. 9-17 
    ISSN: 1432-119X
    Keywords: Key words Silver enhancement ; Immunogold-silver staining ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The immunogold silver staining method (IGSS) is widely used as a sensitive and specific immunohistochemical visualisation technique. IGSS involves the specific deposition of metallic silver at the site of immunogold labelling and provides a means of visualisation at low magnification by light or electron microscopy. Silver developers for IGSS rapidly deposit metallic silver only at the site of heavy metals, including gold and silver, because of their catalytic activity. The developing solution contains the silver ions and reducing agent necessary for this reaction. Using different silver salts as ion donors and by selecting an appropriate temperature and pH, visible amounts of silver can be deposited in a few minutes at the site of colloidal gold labelling while little non-specific background deposition occurs. Inclusion of protective colloids in the solution can also be used to control the reaction. Although studies of the chemical basis of silver deposition around unlabelled colloidal gold date back to 1939, immunogold enhancement by silver was established in 1983. The IGSS method evolved from the combination of disparate photographic, histochemical and immunogold techniques which have been effectively combined and optimised over the last 10 years to provide a visualisation system which is well suited to many immunohistochemical studies.
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  • 51
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    European journal of clinical pharmacology 49 (1996), S. 387-391 
    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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  • 52
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    European journal of clinical pharmacology 47 (1995), S. 507-511 
    ISSN: 1432-1041
    Keywords: Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5–16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg·kg−1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.
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  • 53
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    European journal of clinical pharmacology 47 (1995), S. 525-530 
    ISSN: 1432-1041
    Keywords: Antipyrine disposition ; Obesity ; pharmacokinetics ; oxidative metabolism ; weight reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg · m−2 and 181vs 106 % respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t 1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t 1/2 15.5 vs 12.0 h respectively), but its clearance rate (CLo) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l · kg−1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t 1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CLo. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t 1/2 whereas its CLo is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.
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  • 54
    ISSN: 1432-1041
    Keywords: Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract CHF1194 is an inclusion complex of β-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, β-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-β-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of β-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5′-hydroxypiroxicam and β-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80–125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5′-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with β-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain relief. The pharmacokinetics of piroxicam was linear after the doses used here, suggesting that long term treatment with CHF1194 should not require any change in dosing regimen. Even after 14 days of repeated administration of CHF1194, β-cyclodextrin could not be detected in plasma or urine, suggesting that in man the unchanged oligosaccharide was absorbed to a very small extent.
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  • 55
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    European journal of clinical pharmacology 48 (1995), S. 385-390 
    ISSN: 1432-1041
    Keywords: Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
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  • 56
    ISSN: 1432-1041
    Keywords: Caffeine ; Cardio-green ; Indocyanine Green ; altitude ; metabolism ; pharmacokinetics ; hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardiogreen (ICG) were examined in eight healthy males (23–35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg · kg−1) was administered as an intravenous bolus and caffeine (4 mg · kg−1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in the caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g · 1−1 · min−1), and increased clearance (117 vs 86 ml · min−1 · 70 kg−1). In ALT the area under the curve of ICG significantly decreased (85 vs 207 mg · 1−1 · min−1) and the volume of distribution and clearance increased (5.2 vs 2.41 and 532 vs 234 ml · min−1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.
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  • 57
    ISSN: 1432-1041
    Keywords: Diltiazem ; sustained-release formulation ; pharmacokinetics ; bioavailability ; bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3–4 times a day. A sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in order to allow a single daily administration. Two repeated dosing studies were performed in healthy volunteers. The absolute bioavailability of sustained-release diltiazem LP 300 mg was investigated using concomitant i.v. administration of 13C-labelled drug: absolute bioavailability of the “once a day” formulation was 35%. The second study compared sustained-release diltiazem LP 300 mg with the standard formulation of diltiazem. The results showed that the diltiazem plasma concentrations obtained after the LP formulation remained stable between 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release diltiazem LP 300 mg was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard diltiazem formulation.
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  • 58
    ISSN: 1432-1041
    Keywords: Diabetes ; Human insulin ; Lorazepam ; pharmacokinetics ; glucuronidation ; enterohepatic circulation ; animal insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml·min−1·kg−1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.
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  • 59
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    European journal of clinical pharmacology 48 (1995), S. 273-277 
    ISSN: 1432-1041
    Keywords: Mesalamine ; 5-aminosalicylic acid ; controlled release capsules ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 μg · ml−1 and 1.33 μg · ml−1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.
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  • 60
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    European journal of clinical pharmacology 49 (1995), S. 127-137 
    ISSN: 1432-1041
    Keywords: Thiopental ; Pharmacokinetic modelling ; pharmacokinetics ; single dose ; multiple dosing ; neurosurgical patients ; variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg−1, and the steady-state volume of distribution (Vss) was 2.16 1·kg−1. The distribution (t1/2α) and elimination (t1/2β) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min−1·kg−1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg·1−1 (mean 16.0 mg·1−1 and median 14.3 mg·1−1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg·1−1 (25.4 mg·1−1, and median 23.3 mg·1−1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg−1. The mean Vss was 2.68 1·kg−1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2α was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2β and the mean residence time became longer due to a decrease in clearance. For t1/2β the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml·min−1·kg−1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose. Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.
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  • 61
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    European journal of clinical pharmacology 49 (1995), S. 139-143 
    ISSN: 1432-1041
    Keywords: Intestinal absorption ; Amoxicillin ; pharmacokinetics ; maximum entropy ; input rate
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A computer program applying the principle of maximum entropy to the analysis of drug absorption rate has been developed. Plasma concentrations of amoxicillin obtained after oral and intravenous dosing have been analysed, together with simulated data corresponding to a complex input. Amoxicillin absorption rates devised by the program were similar to those obtained by a standard deconvolution method, although they were displayed as an almost continuous profile. However, improbable fluctuations were obtained with some data sets and the fraction absorbed was underestimated by 13%. With the simulated data, the maximum entropy program did not provide a better solution than the standard deconvolution procedure, and it was sensitive to the addition of random error and to the number of samples. The maximum entropy principle, as implemented in our computer program, may not have a better performance than standard deconvolution procedures, especially in human experiments where the number of blood samples is usually limited.
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  • 62
    ISSN: 1432-1041
    Keywords: Antiallergic drug ; FK613 ; pharmacokinetics ; histamine skin-test ; drug formulation ; urinary excretion ; safety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and 〉89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80–250 ng · ml-1 was recommended to ensure the suppression of histamine-induced wheal by 〉50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.
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  • 63
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    European journal of clinical pharmacology 5 (1972), S. 44-52 
    ISSN: 1432-1041
    Keywords: alprenolol ; serum drug level ; exercise ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of alprenolol on heart rate and systolic blood pressure were studied in healthy subjects during standardized exercise on a bicycle ergometer. In one series of experiments, in which serum concentrations of alprenolol were also measured, the effects of single oral doses of 50, 100 and 200 mg of alprenolol and a placebo were compared by a double blind cross-over technique. In a second series of experiments 100 mg alprenolol was given four times in one day and the effect was followed for up to eighteen hours after the last dose. — Alprenolol diminished the expected increase in heart rate and systolic blood pressure during exercise. The reduction of exercise tachycardia in a given individual was linearly related to the logarithm of the dose or the serum concentration of alprenolol. The serum concentrations required for a given reduction of exercise tachycardia varied almost one hundred-fold amongst the subjects studied. The biological availability of alprenolol was dose-dependent, probably due to a limited capacity biotransformation of the drug before it entered the general circulation. After a single dose the serum level of alprenolol and its chronotropic effect diminished at a rate corresponding to an elimination half life of about two hours. This rate of elimination was consistent with that calculated from the results of the four dose study.
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  • 64
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    European journal of clinical pharmacology 5 (1973), S. 174-180 
    ISSN: 1432-1041
    Keywords: Tricyclic antidepressant ; nortriptyline ; metabolism ; urine ; pharmacokinetics ; twins ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion of nortriptyline (NT) and five of its metabolites was studied by quantitative gas chromatography in 22 twins and 7 unrelated healthy subjects after single (1 mg/kg) and multiple oral doses (0.4 mg/kg t.i.d.) of NT hydrochloride. A mean recovery of 62% of the dose was found after both single and multiple doses. The metabolite pattern in the urine was qualitatively and quantitatively identical in the two regimes, but there were marked variations in the pattern of metabolites between individuals. The disappearance rate of NT from the plasma was mainly determined by the metabolism of NT to 10-hydroxynortriptyline, which varied considerably between individuals. The data suggest that in certain rapid NT metabolizers, the upper limit for the overall clearance of NT from the plasma (if extrahepatic metabolism is assumed to be negligible) might be set by the blood flow through the liver.
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  • 65
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    European journal of clinical pharmacology 52 (1997), S. 235-237 
    ISSN: 1432-1041
    Keywords: Key words Itraconazole ; Coca Cola; acidic beverage ; absorption ; pharmacokinetics ; drug concentration ; food
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To evaluate the effectiveness of Coca-Cola in enhancing the absorption of itraconazole. Methods: Eight healthy volunteers were randomized to receive two treatment sequences in a two-way crossover design with a 1-week wash-out period separating each study treatment. Treatment I, the control, consisted of 100 mg itraconazole with 325 ml water. Treatment II was identical to treatment I, except that itraconazole was administered with 325 ml of Coca-Cola (pH 2.5). Results: Serum itraconazole concentrations, after administration with Coca-Cola (treatment II), were higher than after administration with water (treatment I). The mean AUC was 1.12 vs 2.02 μg · h · ml−1, the mean Cmax was 0.14 vs 0.31 μg · ml −1and the mean tmax was 2.56 vs 3.38 h in treatments I and II, respectively. Conclusion: The absorption of itraconazole can be enhanced by Coca-Cola.
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  • 66
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    European journal of clinical pharmacology 52 (1997), S. 289-292 
    ISSN: 1432-1041
    Keywords: Key words Nicardipine; enantiomers ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. Methods: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a cross-over fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. Results and conclusions: Serum concentration of (+)-nicardipine was approximately 2–3 times higher than that of (−)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3–2.8 times greater than that of the (−)-nicardipine (P 〈 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (−)-nicardipine, respectively, for the 40-mg dose.
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  • 67
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    European journal of clinical pharmacology 52 (1997), S. 379-381 
    ISSN: 1432-1041
    Keywords: Key words Nitroglycerin; transdermal nitrate ; pharmacokinetics ; patch renewal ; exercise test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch treatment for 24 h could induce local cutaneous changes that impaired drug delivery and clinical efficacy. Methods: Twenty angina patients were exercise-tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch was either renewed on a new skin location or on the previous application site in a randomised, double-blind, cross-over protocol. GTN plasma concentrations and finger plethysmography were obtained before and after each exercise test. Results and conclusions: The clinical efficacy, the effect seen on plethysmography and the GTN plasma concentrations tended to increase after patch renewal, regardless of the application site of the renewed patch. Hence, cutaneous changes of clinical importance could not be demonstrated.
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  • 68
    ISSN: 1432-1041
    Keywords: Key words Angiotensin II ; Valsartan; AT1 receptor antagonist ; healthy volunteers ; pharmacokinetics ; renin-angiotensin system ; blood pressure ; passive tilting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pharmacokinetics, pharmacodynamic effects and tolerability of 200 mg valsartan, once-daily for 8 days, were investigated in 16 healthy, normotensive volunteers on a normal sodium diet. Methods: This was a double-blind, placebo-controlled, randomized crossover study. Drug concentrations in plasma and urine, angiotensin II (Ang II) concentrations in plasma, systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) in the supine position and 3 min after passive head-up tilting, as well as safety parameters (ECG, clinical chemistry and hematology, renal water and electrolyte excretion) were measured over 24 h after the first dose (day 1) and at steady state on day 8. Results: Absorption and distribution of valsartan were rapid (Cmax, 2 h; t½λ1 〈 1 h), followed by a slower terminal elimination phase (t½λ2, 6 h) on days 1 and 8, with little accumulation in plasma (increase of 20% on day 8). Less than 10% of the dose was excreted unchanged in urine. The increase in plasma Ang II (Cmax, 6 h) was significantly enhanced at steady state. Supine SBP and DBP significantly decreased on day 8 only, by an average of −3.6 and −2.4 mmHg, respectively, versus placebo, without a concomitant increase in HR. Upon passive tilting, the increase in DBP, normally reinforced by sympathetic renin release, was slightly but significantly blunted on day 1 (−2.0 mmHg) and day 8 (−4.0 mmHg) of treatment with valsartan versus placebo. The orthostatic reflex increase in HR was slightly enhanced compared with placebo by an average of 2.8 beats · min−1 on day 1 and by 2.9 beats · min−1 on day 8. Valsartan was well tolerated and had no influence on ECG, clinical laboratory parameters, and water, electrolyte and uric acid excretion. Conclusions: Pharmacokinetics of valsartan are unchanged after multiple once-daily dosing, with little (expected) accumulation in plasma. Effects of 200 mg valsartan on blood pressure in healthy subjects on a normal sodium intake are small and become more prominent after repeated dosing. Indirect evidence of AT1 blockade by valsartan is demonstrated by an increase of plasma Ang II and by a blunted DBP response to passive tilting. The decrease in blood pressure at steady state enhances the increase in plasma Ang II. Valsartan is well tolerated and is devoid of effects on water, electrolyte and uric acid excretion at 200 mg per day in healthy normotensive volunteers.
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  • 69
    ISSN: 1432-1041
    Keywords: Key words Tiludronate; healthy volunteers ; bisphosphonates ; pharmacokinetics ; calcium metabolism ; bone resorption ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: A double-blind, placebo-controlled study was conducted to assess the pharmacokinetics and pharmacodynamics of the bisphosphonate tiludronic acid, administered once daily as sodium tiludronate 200, 400, 600 and 800 mg for 12 days. Four groups of ten subjects participated in the study, with a drug to placebo ratio of 4:1. Methods: Pre-dose blood samples were taken on alternate days, starting on Day 1 and additional samples were collected over 144 h following the final dose on Day 12. Urine was collected over 24 h after the final dose. Indices of calcium homeostasis and biochemical markers of bone turnover were assessed during the study as pharmacodynamic parameters. Tolerability was evaluated with special emphasis on renal function and gastrointestinal irritation. Adverse experiences were assessed at regular time intervals. Results and conclusions: Steady state was attained from Day 4 (200 mg) or from Day 6 (400, 600 and 800 mg). Following the final dose on Day 12, minimal plasma concentrations (Cmin) ranged between 0.19 and 1.5 mg ⋅ l−1, and maximal plasma concentrations (Cmax) between 1.1 and 7.8 mg⋅l−1 for the lowest and highest doses, respectively. A supra-proportional increase in Cmax, AUC24 and Ae 24 with dose was observed. There was a linear relationship between the plasma tiludronic acid and its urinary excretion rate, so, the disproportional rise in Cmax and AUC24 with increasing dose could not be attributed to saturation of renal excretion. Certain indices of calcium homeostasis changed significantly during the study, but generally, became only prominent at the highest dose level of 800 mg. Total serum calcium and the urinary calcium/creatinine clearance ratio fell, indicating depression of osteoclastic bone resorption, which was not revealed by serum osteocalcin levels probably because of the brevity of the treatment (12 days). In response to the decline in serum calcium, serum 1,25-dihydroxyvitamin D3 and intact PTH (1–84) levels increased. None of the safety parameters raised any concerns about the safety of sodium tiludronate administered in this way.
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  • 70
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    European journal of clinical pharmacology 51 (1996), S. 189-193 
    ISSN: 1432-1041
    Keywords: Key words Dihydropyridine ; Amlodipine ; Grapefruit juice; flavonoids ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: This study was performed to assess whether coadminstration with grapefruit juice significantly affects the pharmacokinetics of amlodipine, a dihydropyridine class calcium antagonist with slow absorption, distribution and low plasma clearance. The primary objective was to evaluate whether short exposure to grapefruit juice could affect the metabolism of amlodipine to an extent similar to that previously demonstrated for other dihydropyridines (e.g. felodipine, nisoldipine, nitrendipine). Methods: Twelve healthy male volunteers followed a randomised, open crossover study design, comparing the effect of a single oral dose of amlodipine (5 mg) taken together with a glass of grapefruit juice (250 ml) vs water. Blood samples to determine plasma concentration were taken and blood pressure (BP) and heart rate (HR) were measured throughout the study. Results: When amlodipine was coadministered with grapefruit juice, Cmax was 115% and AUC(0–72 h) was 116% compared with water, but tmax was not significantly changed. There were no significant differences in BP and HR between the two treatments. A small decrease in diastolic BP, however, was observed in both treatments 4–8 h after drug administration, coinciding with Cmax, but this was normalised after 12 h. The BP reduction seen was compensated by a slight increase in HR, which remained throughout the study. Conclusion: An interaction between grapefruit juice and amlodipine was demonstrated. The haemodynamic data showed that a dose of 5 mg was sufficient to achieve a BP reduction in healthy subjects, but the increase in amlodipine plasma concentration seen after intake of grapefruit juice was too small to significantly affect BP or HR. The clinical significance of this food/drug interaction, however, cannot be ignored since there is considerable variation between individuals and a more extensive intake of grapefruit juice might give more pronounced effects.
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  • 71
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    European journal of clinical pharmacology 51 (1996), S. 259-264 
    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Hypertension; d ; l-enantiomers ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Nebivolol is a selective β1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. Methods: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. Results: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml ⋅ 100 ml−1 tissue) as compared to active nebivolol treatment (5.17 ml ⋅ 100 ml−1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml ⋅ 100 ml−1 tissue) or on active treatment (5.97 ml ⋅ 100 ml−1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). Conclusions: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.
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  • 72
    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
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  • 73
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    European journal of clinical pharmacology 51 (1997), S. 359-366 
    ISSN: 1432-1041
    Keywords: Key words Sufentanil ; pharmacokinetics ; haemo dynamics ; different infusion rates ; coronary surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract    Objective: Pharmacokinetics and haemodynamic effects of a total dose of 15 μg · kg−1 sufentanil, an opioid anaesthetic agent, were studied in patients undergoing aortocoronary bypass surgery at three infusion rates of 30 (group I), 5 (group II), and 2 (group III) μg · kg−1 · min−1, respectively. Results: Plasma concentrations of sufentanil could be optimally characterized by a linear biexponential pharmacokinetic model. Non-compartmental analyses indicated that there was no significant difference in the values of clearance (11.6, 13.3, 14.3 ml · min−1 · kg−1), steady-state volume of distribution (0.220, 0.255 and 0.331 l · kg−1) and mean residence time (18.8, 13.3 and 14.3 min) among the groups. The observed mean Cmax values of 421 (group I), 125 (group II), and 53 (group III) ng · ml−1 and observed mean AUC values from 0 to 3 min were all consistent with the dosing regimens. There were large inter-individual variations in haemodynamic response. Compared to plasma data, a delay in haemodynamic effects was found. Times to reach peak haemodynamic effect ranged from 4.3 to 4.9 min for group I, from 4.6 to 6.1 min for group II, and from 9.9 to 11.3 for group III. Except heart rate, peak haemodynamic effects in these study patients generally ranged from 20.9% to 35.2%. Significant reductions in the area under the effect-time profiles of mean arterial blood pressure and systemic vascular resistance were observed in group II and group III, but not in group I. Significant reductions in the area under the effect-time profiles of left ventricular stroke work index were observed in group III only. No effect on heart rate was found in any group. Conclusion: Our findings suggested that a slower infusion rate of sufentanil at a dose of 15 μg · kg−1 tends to give a greater reduction in mean arterial blood pressure, systemic vascular resistance, and left ventricular stroke work index than does a faster infusion rate.
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  • 74
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    European journal of clinical pharmacology 51 (1997), S. 415-419 
    ISSN: 1432-1041
    Keywords: Key words Midazolam ; Fluconazole ; CYP3A4 ; interaction ; pharmacokinetics ; pharmacodynamics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Midazolam is a short-acting benzodiazepine hypnotic extensively metabolized by CYP3A4 enzyme. Orally ingested azole antimycotics, including fluconazole, interfere with the metabolism of oral midazolam during its absorption and elimination phases. We compared the effect of oral and intravenous fluconazole on the pharmacokinetics and pharmacodynamics of orally ingested midazolam. Methods: A double-dummy, randomized, cross-over study in three phases was performed in 9 healthy volunteers. The subjects were given orally fluconazole 400 mg and intravenously saline within 60 min; orally placebo and intravenously fluconazole 400 mg; and orally placebo and intravenously saline. An oral dose of 7.5 mg midazolam was ingested 60 min after oral intake of fluconazole/placebo, i.e. at the end of the corresponding infusion. Plasma concentrations of midazolam, α-hydroxymidazolam and fluconazole were determined and pharmacodynamic effects were measured up to 17 h. Results: Both oral and intravenous fluconazole significantly increased the area under the midazolam plasma concentration-time curve (AUC0–3, AUC0–17) 2- to 3-fold, the elimination half-life of midazolam 2.5-fold and its peak concentration (Cmax) 2- to 2.5-fold compared with placebo. The AUC0–3 and the Cmax of midazolam were significantly higher after oral than after intravenous administration of fluconazole. Both oral and intravenous fluconazole increased the pharmacodynamic effects of midazolam but no differences were detected between the fluconazole phases. Conclusion: We conclude that the metabolism of orally␣administered midazolam was more strongly inhibited by oral than by intravenous administration of fluconazole.
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  • 75
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    European journal of clinical pharmacology 51 (1997), S. 421-425 
    ISSN: 1432-1041
    Keywords: Key words Warfarin ; Meloxicam ; interaction ; pharmacokinetics ; protein binding
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of multiple oral doses of meloxicam 15 mg on the pharmacodynamics and pharmacokinetics of warfarin was investigated in healthy male volunteers. Warfarin was administered in an individualized dose to achieve a stable reduction in prothrombin times calculated as International Normalized Ratio (INR) values. Then INR- and a drug concentration-time profile was determined. For the interaction phase, meloxicam was added for 7 days and then INR measurements and the warfarin drug profiles were repeated for comparison. Overall, warfarin treatment lasted for 30 days. Results: Warfarin and meloxicam were well tolerated by healthy volunteers in this study. Thirteen healthy volunteers with stable INR values entered the interaction phase. Prothrombin times, expressed as mean INR values, were not significantly altered by concomitant meloxicam treatment, being 1.20 for warfarin alone and 1.27 for warfarin with meloxicam cotreatment. R- and S-warfarin pharmacokinetics were similar for both treatments. Geometric mean (% gCV) AUCSS values for the more potent S-enantiomer were 5.07 mg · h · l−1 (27.5%) for warfarin alone and 5.64 mg · h · l−1 (28.1%) during the interaction phase. Respective AUCSS values for R-warfarin were 7.31 mg · h · l−1 (43.8%) and 7.58 mg · h · l−1 (39.1%). Conclusion: The concomitant administration of the new non-steroidal anti-inflammatory drug (NSAID) meloxicam affected neither the pharmacodynamics nor the pharmacokinetics of a titrated warfarin dose. A combination of both drugs should nevertheless be avoided and, if necessary, INR monitoring is considered mandatory.
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  • 76
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    European journal of clinical pharmacology 52 (1997), S. 391-396 
    ISSN: 1432-1041
    Keywords: Key words Lansoprazole ; CYP2C19; genotype ; hydroxy lation ; polymorphism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations, CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. Methods: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. Results: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1. Conclusion: The hydroxylation of lansoprazole to 5-hydroxylansoprazole was apparently impaired in the subjects with the genetic defects of CYP2C19 (m1/m1 or m1/m2).
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  • 77
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    European journal of clinical pharmacology 6 (1973), S. 268-270 
    ISSN: 1432-1041
    Keywords: Diphenhydramine ; orphenadrine ; gas-liquid chromatography ; N-selective detector ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of nanogram quantities of diphenhydramine and orphenadrine in human plasma. The procedure employs gas-liquid chromatography and a high sensitivity nitrogen detector. It has been used to assay diphenhydramine in plasma after oral administration of therapeutic doses.
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  • 78
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    European journal of clinical pharmacology 6 (1973), S. 234-238 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; neonate ; maternal-fetal exchange ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of phenobarbital were measured in 18 newborn infants for one to two weeks after birth. The drug had been administered prenatally to the mothers as part of treatment for maternal hypertension or toxaemia. The plasma half-life of the drug in the infants (77–404 h) was inversely correlated with the extent of prenatal exposure to it. In three infants a bi-phasic plasma curve was found as there was a sudden change from slow to fast disappearance on the 5th to 7th day of life.
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  • 79
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    European journal of clinical pharmacology 7 (1974), S. 407-414 
    ISSN: 1432-1041
    Keywords: Diuretic ; indapamide ; human pharmacology ; toxicology ; pharmacokinetics ; TLC assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na+, K+ and Cl− and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca2+, Mg2+ and PO 4 3− rose in spite of a fall in urinary concentrations of these ions. The Ca2+ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.
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  • 80
    ISSN: 1432-1041
    Keywords: Oral antidiabetic drug ; butylbiguanide ; pharmacokinetics ; two-compartment open model ; plasma concentration ; liver concentration ; intestine concentration ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 50 mg14C-Butylbiguanide was administered intravenously to 4 diabetic patients and 100 mg14C-butylbiguanide orally to 5 further diabetics. The concentrations of the drug in plasma, intestinal fluid, intestinal epithelium and liver tissue were determined and the renal excretion of the biguanide measured. Irregularities in the plasma concentration curve were observed which appeared as systematic deviations from the ideal curve of a biexponential function. Because these deviations occurred only in the middle phase of the plasma concentration curve, it was nevertheless possible to calculate the pharmacokinetic parameters of butylbiguanide by use of a two-compartment open model. The principal pharmacokinetic parameters were determined according to this model after intravenous dosing and the following mean values were obtained:t 1/2 (β)=4.6 h (β=0.15 h−1),C P 0 =0.85µg/ml,V D =218 l,V T =157 l,V P =62 l,k 12=0.69 h−1,k 21=0.44 h−1,k el =0.54 h−1. Within 48 h after administration, an average of 72.4% of the intravenous and 74.4% of the oral dose had been excreted in the urine. Total clearance (Cl tot) averaged 536 ml/min and renal clearance (Cl ren) 393 ml/min. High concentrations of butylbiguanide were observed in the intestinal fluid (100–700 mg/ml) 20–40 min after oral administration. It was found that the drug accumulates in intestinal fluid, intestinal epithelium and liver tissue, and that it is secreted into the intestinal lumen. The concentrations of butylbiguanide in intestinal and liver tissue were 10–46 times higher than in plasma. The secretion of biguanide into the intestinal lumen may occur via the bile or the intestinal mucosa, but there is no evidence of significant biliary excretion of butylbiguanide.
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  • 81
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    European journal of clinical pharmacology 7 (1974), S. 295-305 
    ISSN: 1432-1041
    Keywords: Mestranol ; ethynyloestradiol ; contraceptive compounds ; demethylation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oestrogenic activity of mestranol depends on its demethylation to ethynyloestradiol. The reaction has been studied in man. The compound disappeared exponentially from plasma during the first 4 h after i.v. injection of [4-14C-] mestranol. The “metabolic clearance” for this phase amounted to 31.8 1/day per kg body weight. Methoxy-3H-labelled mestranol was prepared for the further studies, because if it is demethylated, the tritium would be transferred to HTO, which would equilibrate immediately with body water. The appearance in body water of tritium from [methoxy-3H-] mestranol could be described by two exponential functions, which corresponded to bi-phasic disappearance of the original compound from plasma. The rate constant of the first stage was: γ1=0.835 h−1, and of the second: γ2=0.034 h−1. HTO radioactivity was eliminated from the body by exchange of water. From the data obtained, a three-compartment model was constructed of the transfer of tritium from [methoxy-3H-] mestranolinto body water, which permitted computer simulation of the partial processes. The compartmental analysis suggested that mestranol differed from ethynyloestradiol mainly in the delayed and protracted manner in which hormonally active oestrogen entered the circulation. The proportion of [methoxy-3H-] mestranol demethylated to ethynyloestradiol (demethylation ratio) varied little, 53.7±5.0% (x±SD; n=6), and was consistent with clinical observations that mestranol is half as potent an oestrogen as ethynyloestradiol. Thus, the dose of mestranol required to produce a given effect has to be twice as large as that of ethynyloestradiol.
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  • 82
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    European journal of clinical pharmacology 6 (1973), S. 44-53 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; plasma clearance ; gas chromatography — mass spectrometry ; pharmacogenetics ; twins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five identical (monozygotic) and 6 fraternal (dizygotic) sets of healthy twins between 47 and 53 years of age were given a single oral dose of nortriptyline (NT) hydrochloride 1 mg/kg. The plasma half-life, the apparent volume of distribution, and the plasma clearance of NT were estimated for each subject as well as the urinary excretion rate of conjugated and unconjugated 10-hydroxynortriptyline (10-OH-NT). “Steady-state” plasma levels predicted from the reciprocal single dose plasma clearance rate of NT agreed well with those observed in a previous study of the same twins 2 years previously. In the present study, there was a 5-fold range of the plasma half-lives and 2-fold variation in the apparent volume of distribution of NT (assuming complete availability on oral administration). No correlation was found between the plasma half-life and the apparent volume of distribution. Analysis of variance showed that most of the variability between persons in plasma half-life, apparent volume of distribution and conjugation of 10-OH-NT was genetically determined. The plasma half-life and apparent volume of distribution may contribute independently to the total interindividual variability of the “steady-state” plasma level of NT.
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  • 83
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    European journal of clinical pharmacology 4 (1971), S. 54-58 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; infusion ; plasma expander ; blood level fluctuation ; sulfonamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary A hypothetical pharmacokinetic model is reported which describes the decreasing fluctuations in the blood levels of a sulfonamide during infusion of a plasma expander. Its concentration in the serum increases reciprocally with the amount of plasma expander infused. These procedures can be described by simple equations, and it is possible therefore, to calculate the dose required to maintain a constant blood level during the infusion.
    Notes: Zusammenfassung Es wird über ein hypothetisch-pharmakokinetisches Modell berichtet, welches sich mit der absinkenden Serumkonzentration eines Sulfonamids nach Infusion eines Plasmaexpanders beschäftigt. Die Serumkonzentration fällt reziprok zur infundierten Menge des Plasmaexpanders ab. Die Vorgänge lassen sich durch einfache Gleichungssysteme beschreiben. Es gelingt daher, eine Zusatzdosis zu berechnen, welche den bei Infusionsbeginn bestehenden Plasmaspiegel annähernd konstant erhält.
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  • 84
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    European journal of clinical pharmacology 49 (1996), S. 387-391 
    ISSN: 1432-1041
    Keywords: Liver function tests ; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h·l−1, clearance was reduced (5.0 vs. 11.8 l·h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r=0.41, P=0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r=0.94, P〈0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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  • 85
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    European journal of clinical pharmacology 49 (1996), S. 411-415 
    ISSN: 1432-1041
    Keywords: Moxisylyte ; pharmacokinetics ; intracavernous administration ; healthy volunteers ; adverse events ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The concentration-time profiles of specific metabolites of moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). Results: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. Conclusion: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.
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  • 86
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    European journal of clinical pharmacology 47 (1995), S. 543-548 
    ISSN: 1432-1041
    Keywords: Sumatriptan ; pharmacokinetics ; single dose ; bioavailability ; dose proportionality ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavilability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 1) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.
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  • 87
    ISSN: 1432-1041
    Keywords: Granisetron ; pharmacokinetics ; elderly ; tolerance
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  • 88
    ISSN: 1432-1041
    Keywords: Growth hormone ; Jet-injection ; pharmacokinetics ; pharmacodynamics ; Somatomedin C ; free fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108 – 142). The AUC0−∞ for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93 – 103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.
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  • 89
    ISSN: 1432-1041
    Keywords: Losartan ; Cimetidine ; pharmacokinetics ; plasma renin activity
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I·ml−1·h−1 without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.
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  • 90
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    European journal of clinical pharmacology 48 (1995), S. 501-504 
    ISSN: 1432-1041
    Keywords: Quinidine ; CYP2D6 ; Sparteine oxidation polymorphism ; (3S)-3OH-quinidine ; quinidine-N-oxide ; dihydroquinidine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l·h−1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l·h−1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.
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  • 91
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    European journal of clinical pharmacology 49 (1995), S. 221-228 
    ISSN: 1432-1041
    Keywords: Nefazodone ; Geriatric assessment ; Hepatic cirrhosis ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The single-dose pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were examined in 12 healthy younger subjects ≤55 years of age (YNG), 12 elderly subjects ≥65 years of age (ELD), 12 patients with biopsy proven hepatic cirrhosis (HEP) and 12 patients with moderate renal impairment (REN), ClCR 20–60 ml·min−1. The study was of parallel group design, with each of the four subject groups receiving escalating single oral doses of 50, 100 and 200 mg of nefazodone at 1 week intervals. Serial blood samples for pharmacokinetic analysis were collected for 48 h following each dose and plasma samples were assayed for NEF, HO-NEF and mCPP by a validated HPLC method. Single oral doses up to 200 mg of nefazodone were well tolerated by all subjects. Maximum plasma levels of NEF and HO-NEF were generally attained within 1 h after administration of nefazodone. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively. There were no apparent gender-related pharmacokinetic differences in any group of subjects. NEF and HO-NEF pharmacokinetics were dose dependent in all four subject groups; a superproportional increase in AUC and an increase in t1/2 with increasing dose was obtained, indicative of nonlinear pharmacokinetics. Relative to normal subjects, elderly and cirrhotic subjects exhibited increased systemic exposure to NEF and HO-NEF, as reflected by AUC, at all doses of nefazodone; subjects with moderate renal impairment did not. Elderly and cirrhotic patients may require lower doses of NEF to achieve and maintain therapeutic effectiveness.
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  • 92
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    European journal of clinical pharmacology 49 (1995), S. 229-235 
    ISSN: 1432-1041
    Keywords: Nefazodone ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The steady-state pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were compared in subjects with normal and impaired renal function. Patients: The Study was of parallel group design which included 7 subjects with normal (NOR) renal function, CLCR≥72 ml·min−1·1.73 m−2, 6 with moderate (MOD) renal impairment, CLCR 31–60 ml·min−1·1.73 m−2 and 9 with severe (SEV) renal impairment, CLCR≤30 ml·min−1·1.73 m−2. Subjects in each renal function group received a 100-mg oral dose of nefazodone hydrochloride BID for 7 days and a single morning dose on day 8. Starting 48 h after the last 100-mg dose, 200-mg doses were administered on a similar schedule to 3, 4 and 3 subjects from each renal function group (NOR, MOD and SEV, respectively). Single trough blood samples just prior to each morning dose (Cmin) and serial samples after the dose on day 8 were obtained at each dose level for pharmacokinetic analysis. Plasma samples were assayed by a specific HPLC method for NEF, HO-NEF and mCPP. The CMIN data indicated that steady state was attained by the third day of BID administration of both the 100- and 200-mg doses of nefazodone, regardless of degree of renal function. Both NEF and HO-NEF attained steady-state Cmax within 2 h after administration of nefazodone; tmax for mCPP was less defined and more delayed. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively, regardless of the status of renal function. Steady-state systemic exposure of NEF and HO-NEF, as reflected by AUC and Cmax, and elimination t1/2 values did not differ significantly among renal function groups. Conclusion: The study results suggest that dose adjustments may not be necessary, but nefazodone should be used with caution in the presence of severe renal impairment.
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  • 93
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    European journal of clinical pharmacology 49 (1996), S. 293-298 
    ISSN: 1432-1041
    Keywords: Key words Budesonide; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol ⋅ l−1 (0.95–8.2), 3.0 nmol ⋅ l−1 (0.64–8.9) and 1.3 nmol ⋅ l−1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax = 2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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  • 94
    ISSN: 1432-1041
    Keywords: Felodipine ; pharmacokinetics ; haemodynamics ; congestive heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In congestive heart failure patients the kinetics of felodipine, a dihydropyridine calcium antagonist, show interpatient differences after acute i.v. administration that disappear after 8 weeks oral treatment with a change in kinetics in the patients with the largest clearances (CL) and the smallest volumes of distribution (V SS). Pharmacokinetic and haemodynamic data were combined to construct a haemodynamic-pharmacokinetic model. This model shows that the differences between the patients in i.v. pharmacokinetics are consistent with a difference in plasma flow distribution between liver and poorly perfused tissues. In patients in whom kinetics changed, felodipine treatment is supposed to cause a redistribution of flow from liver to peripheral tissues, accompanied by a decreased work load of the heart and a larger increase in VO2max during therapy than in the other patients, whose workload increased. This suggests a better therapeutic response in the patients whose kinetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might be predictive for the therapeutic effect of felodipine.
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  • 95
    ISSN: 1432-1041
    Keywords: Cholesterol acyltransferase ; Hypocholesterolaemic ; 447C88 ; volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 447C88 (N-Heptyl-N′-(2,4 difluoro-4-6-(2(-4-(2,2 dimethylpropyl)phenyl)ethyl)phenyl)urea) is an inhibitor of human microsomal AcylCoA:Cholesterol acyltransferase (ACAT) with an IC50 of 10.2 ng·ml−1 (23 nM). It is poorly absorbed but 5 mg·kg−1·day−1 completely abolishes the rise in plasma cholesterol in cholesterol-fed rats. In this study, twelve healthy, male volunteers received single, oral doses of 25, 50, 100, 200, 400 and 800 mg of 447C88 (n+8) or placebo (n+4) with food in a double-blind study with at least a week between occasions. The 400 mg dose was repeated after an overnight fast. Subsequently, fourteen different volunteers received a single 200 mg dose of 447C88 (n+8) or placebo (n+6) with food and, a week later, the same dose twice daily for 10 days; all doses were given with food. All doses were well tolerated with no significant changes in vital signs, full blood counts or plasma biochemical profiles. Plasma concentrations of 447C88 were unquantifiable after the fasting dose and low after all other doses. Mean Cmax and AUC were 1.8 ng·ml−1 and 9.0 ng·ml−1·h after 200 mg rising to 5.4 ng·ml−1 and 23.8 ng·ml−1·h respectively after 800 mg; t1/2 was 1.3 to 5.2 h. After 10 days dosing, plasma 447C88 concentrations were higher in the evening than the morning probably due to administration of the evening dose with more food. There were no significant changes in plasma triglcerides or total, LDL- or HDL-cholesterol after dosing with 447C88.
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  • 96
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    European journal of clinical pharmacology 49 (1996), S. 293-298 
    ISSN: 1432-1041
    Keywords: Budesonide ; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95–8.2), 3.0 nmol·l-1 (0.64–8.9) and 1.3 nmol·l-1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax=2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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  • 97
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    European journal of clinical pharmacology 49 (1996), S. 317-323 
    ISSN: 1432-1041
    Keywords: Magnesium ; Plasma level ; pharmacokinetics ; bioavailability ; circadian fluctuation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
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  • 98
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    European journal of clinical pharmacology 5 (1972), S. 58-61 
    ISSN: 1432-1041
    Keywords: Pralidoxime chloride ; pharmacokinetics ; anti-cholinesterase poisoning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose of 1.0 g (10.0–14.0 mg/kg body weight) of pralidoxime mixed with various cholinolytics was given by i.m. injection to 29 healthy male subjects. A concentration of pralidoxime in blood of 4 µg/ml was reached after 5 to 10 min with all the mixtures and was maintained for about 1 to 2 h. The calculated half lives of pralidoxime in three groups of subjects were 62.2, 60.0 and 61.8 min., respectively. — The urinary excretions of pralidoxime during the first 4 h after the injections averaged 75.0, 79.6 and 69.6 per cent, respectively, of the total amount given. — The results are compared with published information about similar oximes.
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  • 99
    ISSN: 1432-1041
    Keywords: Key words Tolcapone ; Elderly; levodopa ; pharmacokinetics ; pharmacodynamics ; multiple-dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Methods: The drug was administered orally t.i.d. for 7 days to four sequential groups of eight elderly subjects (gender ratio1:1) at doses of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled, ascending-multiple-dose design. On days 2 and 7, a single dose of levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone. Plasma concentrations of tolcapone, its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa were determined during the course of the study in conjunction with COMT activity in erythrocytes. Results: Tolcapone was well tolerated at all dose levels, with a slight increase in gastrointestinal adverse events in females at higher doses. The drug was rapidly absorbed and eliminated and showed no changes in pharmacokinetics with time during multiple doses of 100 and 200 mg t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as reflected in increased Cmax and AUC values. Despite the long half-life of 3-O-methyltolcapone (39 h), only minor accumulation occurred due to suppression of its formation by tolcapone. The pharmacodynamics of tolcapone did not change during the week of treatment as reflected in inhibition of COMT activity in erythrocytes, the derived parameters of the plasma concentration-effect relationship (inhibitory Emax model with constant EC50 values) and the effect on levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This suggests the absence of tolerance development and the insignificance of the altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the pharmacodynamics. Conclusion: The results of this study offer promising perspectives for the application of tolcapone as adjunct therapy to levodopa in the treatment of Parkinson’s disease.
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  • 100
    ISSN: 1432-1041
    Keywords: Key words Cilazapril ; Caucasians ; Chinese; cilazaprilat ; pharmacokinetics ; pharmacodynamics ; ACE inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Methods: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian, healthy, normotensive volunteers on their normal diet. Cilazapril was given orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE-activity. Plasma concentrations of the active drug were measured by radioimmunoassay. Blood pressure and heart rate were measured at regular intervals. Results: The pharmacokinetic parameters of cilazaprilat were similar in the two ethnic groups. No significant difference in plasma concentrations was found at any of the time points. However, the weight-adjusted plasma clearance was significantly higher in the Chinese group, which is compatible with their lower body weight. The effects on plasma hormones were also comparable, although there was a somewhat greater rise in PRA and greater fall in aldosterone levels in Chinese than in Caucasians. The effect of cilazapril on blood pressure and heart rate was greater than was previously reported in healthy volunteers. Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in both groups, but there was a more prolonged reduction in DBP in Caucasians. In addition, heart rate (HR) was significantly increased from baseline from 5 h onwards in Chinese subjects and significantly higher in comparison with Caucasians at most time points from 1.5 h onwards. The pharmacokinetic parameters of cilazapril were essentially the same in healthy, normotensive Chinese and Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good tolerance. The inhibition of ACE in relationship to time and the plasma concentrations of cilazaprilat were similar in the two groups, although the changes in PRA and aldosterone suggest an ethnic difference in the responses of the renin-angiotensin-aldosterone system.
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