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We report an optical parametric amplifier (OPA), providing a maximum pulse energy of ∼200 µJ at 700-950 nm and a pulse duration of ∼1 ps. The OPA is driven by a ∼1 ps pulse with ∼2.5 mJ energy at 1 kHz, provided by a commercial thin-disk based laser. Using the output pulse of the OPA as pump, the thin-disk laser pulses at 1030 nm as Stokes, and the second harmonic (515 nm) as probe, we investigate the coherent anti-Stokes Raman scattering (CARS) of N

We investigate the spectral properties of ps laser-induced filamentation in air using an ultrafast thin-disk based amplifier at a central wavelength of 1030 nm with a maximum pulse energy of 60 mJ at a repetition rate of 1 kHz. We show that the spectrum induced by filamentation in air is sufficiently broad to excite ro-vibrational Raman transitions in N2, O2 and CH4. The excitation is probed with the second harmonic (515 nm) to generate CARS signals in air. Furthermore, we investigate the influence of optical windows on the CARS signal for applications in combustion and gasification diagnostics.

We investigate the coherent anti-Stokes Raman scattering (CARS) in air generated by the spectral broadening of laser induced filamentation at a pulse duration of ~1 ps and a central wavelength of ~1 μm.

Coherent anti-Stokes Raman spectroscopy (CARS) is a powerful tool in combustion diagnostics [1] . It requires three beams, the pump, Stokes and probe beam with at least two different wavelengths. For high pressure applications, the use of fs-pulses is of additional benefit, as the CARS signal is free from distortions from molecular collisions, if the excited Raman level is probed within a few ps [2] . On the other hand, too short pulses (~100-500 fs) result in poor spectral resolution [3] . In this study, we present an optical parametric amplifier (OPA), providing a maximum pulse energy of ~200 µJ, at 700-900 nm and a pulse duration of ~1 ps. Using a pump source at 1030 nm, this setup may serve as a customized fs-CARS system for high pressure gas analysis.

We investigated ultrashort pulse filamentation and lasing action of

Due to ageing populations the number of tumors is increasing worldwide. Successful surgical treatment requires complete resection of tumors to reduce recurrence rates. To reach this goal, novel methods combining in vivo tumor and tumor margin detection with low invasive precision surgical tools are needed. Coherent anti-Stokes Raman scattering (CARS) imaging is a highly promising optical tool for visualizing tumors based on characteristic changes in tissue morphology and molecular composition, while fs-laser ablation is to date the most precise surgical tool established in ophthalmology. In this contribution, CARS imaging has been combined with fs-laser ablation as a new approach for image-guided precision surgery for the first time. CARS guided fs-ablation has been applied to ablate brain, liver, skin, muscular and vascular tissues with μm-precision using sub-100 fs pulses of μJ level. We demonstrate superior imaging performance and contrast as well as detection of tissue margins by coherent Raman microscopy in comparison to laser reflectance imaging. The combination of CARS-image-guided tissue ablation is a promising tool for minimally invasive surgeries particularly in the vicinity of functional structures in the future.

The newly developed HITECOM reactor provides the possibility of in-situ analysis of single particle reactions. It combines the capabilities of a magnetic suspension thermobalance with state of the art optical analysis. The surface temperature and carbon conversion of single particles are measured under well-defined flow conditions. The generated data enables the detailed validation of CFD single particle models. For this reactor, a special temperature resistant particle holder had to be constructed, which is able to fix various particles in direct flow during gasification. An in-situ Raman spectroscopy setup was established for quantitative gas analysis at pressures between 1 and 20 bar and temperatures up to 965 °C. Here, a pulsed Nd:YAG laser at 355 nm was used as excitation source. The Rayleigh/Raman scattering was measured perpendicular to the flow direction with a spectrograph and ICCD camera. From the recorded spectra the gas concentrations were calculated. Generally, the calculated concentrations of CO, CO2 and N2 match the reference values from the gas chromatograph. In the present study, single coal particles of one Central German lignite and one hard coal were analyzed and monitored during gasification. The particle diameter ranged from 1 to 3 mm. Gasification experiments with CO2 were carried out under isothermal conditions at 1 bar total pressure and temperatures of 800–1200 °C. The experimental data were adjusted with models by data fitting. It was found that the Random Pore Model (RPM) matches the carbon conversion of the hard coal sample and the Shrinking Core Model (SCM) matches the carbon conversion of the lignite sample. Further analysis revealed that inhomogeneous particles affect gasification kinetics. The differences in reactivity between several particles from the hard coal are significantly larger than for the lignite particles, which is in accordance to the results of the respective ultimate and proximate analyses. Additionally, it was discovered that the difference between gas and particle temperature is negligible for low reactive feedstocks within the investigated temperature range (ΔT ⩽ 5 K at 1070 °C, hard coal), whereas there was a significant difference for reactive particles (ΔT ⩽ 40 K at 1070 °C, lignite).

We propose a method using the non-resonant signal measured in pure argon for gas concentration measurements based on ultrabroadband fs/ps coherent anti-Stokes Raman scattering. Measurement accuracies are greatly improved to 5% for CO2/N2/CH4 gas mixtures.

Due to their large spectral bandwidth sub ∼20 fs pulses are a versatile tool in spectroscopy, but for applications in gases comparably high pulse energies are required. These pulses are easily subject to distortions of the spectral shape, phase and shot-to-shot stability. We investigate the excitation efficiency for two-beam ultrabroadband fs/ps coherent anti-Stokes Raman scattering (CARS) using a shot-to-shot stable BBO-based optical parametric chirped pulse amplifier (OPCPA). Up to 10 bar, quantitative concentration measurements with and without consideration of the excitation efficiency measured in argon are investigated for ternary gas mixtures with Raman shifts up to ∼3000 cm−1.

The test reactor HITECOM was designed to study in situ the conversion of an isolated particle in a well-defined gas flow at a gas temperature up to 1400 ° C and a pressure up to 40 bar. As is typical of high-temperature, high-pressure systems, the temperature field inside the reactor is not perfectly constant and causes natural convection, which interferes with the gas flow in the test rig. To gain a deeper insight into the complex flow field and temperature and species distribution, a detailed CFD study was carried out and the results validated against experimental data. The numerical model comprised reactive gas flow, heat and mass exchange with a reactive char particle, convective and radiative heat transfer in the reactor and heat conduction in the solid parts of the reactor. The present study revealed that, depending on the operating conditions, the flow field shifts from an idealized parabolic profile to a complex, buoyancy-driven flow. It could be shown that comprehensive CFD modeling is necessary to identify critical operating conditions and estimate the real species and temperature distribution around the reacting particle, facilitating an improved evaluation of the experimental data.

Femtosecond (fs)-CARS is a promising approach for gas spectroscopy under high pressure and temperature conditions, as it allows probing molecular states on a time scale which is significantly shorter than the typical decay time induced by interfering collisions. Usually, fs-CARS is performed in a three beam setup, which requires maintaining spatial and temporal overlap of the pulses at the focal point. This is a challenging task, especially in harsh environments such as in a combustion chamber. In this study, we present an alternative approach, which uses two beams in a collinear configuration. An ultra-broadband, sub 7 fs laser pulse acts as pump and Stokes pulse, and a ∼500 fs pulse is used for probing. We show that this configuration is suitable for measuring the gas temperature and concentration. Furthermore, possible single shot measurements of the gas temperature are evaluated.

We investigated ultrashort pulse filamentation and lasing action of N 2 + for pump-probe experiments in gases. Using femtosecond coherent anti-Stokes Raman scattering, the white-light supercontinuum generated in the filament was used to excite ro-vibrational Raman transitions in air, C O 2 and C H 4 . We show that the lasing pulse acts as a probe for the excited levels by detecting the corresponding anti-Stokes Raman spectroscopy signals. This feature may be applied to remote sensing applications, as the temporal and spatial alignment of the probe beam and the filament is intrinsically provided.

Using two beam femtosecond coherent anti-Stokes Raman scattering (fs-CARS), temperature and concentration measurements are performed on relevant combustion species such as H2, N2, CO, and CO2.

Background and Objective To investigate femtosecond (fs)-laser patterns within ocular media for ophthalmic surgery. Methods Vitreous and crystalline lens tissue from porcine eyes were treated with 2-dimensional fs-laser patterns and inspected under the optical microscope. Time resolved pump-probe experiments were conducted on vitreous tissue and gelatin, which should act as a model for crystalline lens tissue. Results Within crystalline lens tissue, pulse overlap leads to the formation of large bubbles, which is caused by subsequent energy input from the surrounding plasma channel. This effect can be used for bubble size control. Vitreous tissue behaves similar to water under fs-laser treatment, but it still allows fs-laser cutting. Conclusion Bubble size control by laser bursts may reduce optical side-effects of fs-laser treatment. Furthermore, fs-laser treatment could be used for vitreoretinal applications. Lasers Surg. Med. 45:589–596, 2013. © 2013 Wiley Periodicals, Inc.

International audience; Ultrashort pulse lasers enable reliable and versatile high precision ablation and surface processing of various materials such as metals, polymers and semiconductors. However, when modifications deep inside the bulk of transparent media are required, nonlinear pulse material interactions can decrease the precision, since weak focusing and the long propagation of the intense pulses within the nonlinear media may induce Kerr self-focusing, filamentation and white light generation. In order to improve the precision of those modifications, simultaneous spatial and temporal focusing (SSTF) allows to reduce detrimental nonlinear interactions, because the ultrashort pulse duration is only obtained at the focus, while outside of the focal region the continuously increasing pulse duration strongly reduces the pulse intensity. In this paper, we review the fundamental concepts of this technology and provide an overview of its applications for purposes of multiphoton microscopy and laser materials processing. Moreover, numerical simulations on the nonlinear pulse propagation within transparent media illustrate the linear and nonlinear pulse propagation, highlighting the differences between conventional focusing and SSTF. Finally, fs-laser induced modifications in gelatine are presented to compare nonlinear side-effects caused by conventional focusing and SSTF. With conventional focusing the complex interplay of self-focusing and filamentation induces strongly inhomogeneous, elongated disruptions. In contrast, disruptions induced by SSTF are homogeneously located at the focal plane and reduced in length by a factor >2, which is in excellent agreement with the numerical simulations of the nonlinear pulse propagation and might favor SSTF for demanding applications such as intraocular fs-laser surgery.

To investigate the long-term stability and possible cataractogenesis after femtosecond laser treatment of the crystalline lens.The crystalline lenses of ten Göttingen minipigs® underwent femtosecond laser treatment. During a subsequent 1-year follow-up, the pigs were monitored by means of slit-lamp examination of the anterior segment and Scheimpflug imaging of the lens.No laser-induced cataractogenesis was observed during the 1-year follow-up. The laser pattern showed a stable appearance under all examination devices.Femtosecond laser treatment seems to be no trigger for cataract formation. Moreover, the long-term stability of the laser pattern makes it suitable for applications such as presbyopia treatment.

We analyze the temperature in air and neat N2 under high pressure using ultrabroadband, two-beam femtosecond coherent Anti-Stokes Raman scattering. The derived temperatures are compared to numerical simulations.

In der Literatur gibt es eine Reihe von Hinweisen, die auf ein unzureichendes strategisches Management in kleinen und mittelstandischen Unternehmen (KMU) im deutschen Sprachraum hindeuten. Im vorliegenden Beitrag erfolgt eine gestaltungsorientierte aktuelle Bestandsaufnahme konzeptioneller und empirischer Gegebenheiten mit Fokus auf Schweizer KMU der ICT-Branche. Ausgehend von einer Kennzeichnung von Grundorientierung, Prozess und Denkperspektiven des strategischen Managements und einem situations- und evolutionstheoretischen Zugang zur strategischen Fuhrung werden die wichtigsten Aspekte einer Umsetzung des strategischen Managements in KMU thematisiert: dessen Verbreitung und Eignung, die Rolle der Fuhrungskrafte, die Relevanz des strategischen Denkens sowie Planungsformen und Instrumente. Die empirische Bestandsaufnahme erfolgt im Kern uber eine qualitative Erhebung bei zehn Fuhrungskraften Deutschschweizer ICT-KMUs, die durch eine quantitative internetbasierte Befragung von Fuhrungskraften der Schweizer ICT-Branche rudimentar erganzt wird. Die Ergebnisse deuten auf eine derzeit noch unzureichende Umsetzung des strategischen Managements und auf situative, flexiblere Implementierungsansatze bei den untersuchten Deuschschweizer ICT-KMU hin. Vor dem Hintergrund eines erkannten Differenzierungsbedarfs werden spezifische Handlungsempfehlungen zum strategischen Management fur KMU der ICT-Branche abgeleitet.

International audience; We report new experimental and numerical results on supercontinuum generation at ultraviolet/visible wavelengths produced by the propagation of infrared femtosecond laser pulses in air. Spectral broadening is shown to similarly affect single filaments over laboratory distance scales, as well as broad beams over long-range propagation distances. Numerical simulations display evidence of the crucial role of third harmonic generation in the build-up of UV-visible wavelengths, by comparison with current single-envelope models including chromatic dispersion and self-steepening.

International audience; In recent years, femtosecond (fs)-lasers have evolved into a versatile tool for high precision micromachining of transparent materials because nonlinear absorption in the focus can result in refractive index modifications or material disruptions. However, when high pulse energies or low numerical apertures are required, nonlinear side effects such as self-focusing, filamentation or white light generation can decrease the modification quality. In this paper, we apply simultaneous spatial and temporal focusing (SSTF) to overcome these limitations. The main advantage of SSTF is that the ultrashort pulse is only formed at the focal plane, thereby confining the intensity distribution strongly to the focal volume and suppressing detrimental nonlinear side effects. Thus, we investigate the optical breakdown within a water cell by pump-probe shadowgraphy, comparing conventional focusing and SSTF under equivalent focusing conditions. The plasma formation is well confined for low pulse energies

Objective: In this feasibility study, we investigate possible femtosecond laser thrombolysis. Background data: Because of low pulse energies, femtosecond laser surgery inherently minimizes side effects on the surrounding tissue. Moreover, current femtosecond laser sources as well as fiber technology allow consideration of catheter-based treatments. Methods: Two femtosecond laser systems (?=800 nm, ?=1030 nm) along with a three dimensional (3D) scanner system (NA 0.1) were used in this study. In vitro experiments were performed on porcine thrombi and blood vessels. Ablation thresholds were determined in air, by determining the pulse energy at which single shot ablation was visible under the optical microscope. Ablation rates were determined in physiological saline. Additionally, ablation of thrombi and blood vessels was monitored by means of a fiber spectrometer. Results: Depending upon the scan velocity, typical ablation rates for thrombi were 0.04 mm3/sec. Ablation thresholds of thrombi and blood vessels differ by factors of 3 and 1.5 at laser wavelengths of 800 and 1030 nm, respectively. At a distance of 5 mm above the surface, second harmonic generation was observed in blood vessels, but not within thrombi. Conclusions: The results show that a typical thrombus volume can be destroyed within a reasonable time frame. Because of the higher threshold difference of thrombi and blood vessels, the use of a laser wavelength of 800 nm is preferable. Furthermore, the detection of the second harmonic could provide a feedback mechanism to protect the vascular wall from mechanical and laser damage.

To investigate femtosecond (fs)-laser patterns within ocular media for ophthalmic surgery.Vitreous and crystalline lens tissue from porcine eyes were treated with 2-dimensional fs-laser patterns and inspected under the optical microscope. Time resolved pump-probe experiments were conducted on vitreous tissue and gelatin, which should act as a model for crystalline lens tissue.Within crystalline lens tissue, pulse overlap leads to the formation of large bubbles, which is caused by subsequent energy input from the surrounding plasma channel. This effect can be used for bubble size control. Vitreous tissue behaves similar to water under fs-laser treatment, but it still allows fs-laser cutting.Bubble size control by laser bursts may reduce optical side-effects of fs-laser treatment. Furthermore, fs-laser treatment could be used for vitreoretinal applications.

Femtosecond lasers are a versatile tool to process transparent materials like glasses, polymers or ophthalmic tissue. However, when focusing pulses of several μJ into the material, the high intensity near the laser focus leads to undesired nonlinear side effects like self-focusing and filamentation, resulting in an increased length of the induced plasma or the fragmentation of the breakdown volume. To overcome this limitation, we studied the influence of simultaneous spatial and temporal focusing (SSTF) on the laser induced optical breakdown (LIOB) in water. For this purpose, the incoming laser pulse is spectrally separated by a grating stretcher setup and recompressed by the focusing optics. Due to the increased pulse duration outside of the laser focus, the nonlinear laser-material interaction is confined to the focal region. We investigated the formation of the plasma and the resulting disruption in water by shadow imaging. With conventional focusing (τ = 70 fs, NA = 0.1) self-focusing, filamentation and breakup of the disruption volume was observed for pulse energies > 2 μJ, leading to a breakdown length of ~ 800 μm at a pulse energy of 8 μJ. With SSTF the axial length of the breakdown is significantly reduced by a factor of ~ 2. Plasma formation and the resulting disruption stay within the focal region. No self-focusing could be observed for pulse energies up to 8 μJ. Therefore, SSTF appears to be a promising tool to induce photodisruptions in transparent materials even with low numerical aperture, e.g. for precise fs-laser surgery within the posterior segment of the eye.

We show that two-beam femtosecond coherent anti-Stokes Raman scattering can be effectively used for thermometry on CO2 for temperatures between ∼100 °C and ∼600 °C at a maximum pressure of 8.5 bar. The temperature measurement is based on probing the vibrationally excited states of CO2, using a ∼7 fs pump/Stokes pulse and a narrowband (∼0.3 nm) probe pulse. The temperatures can be derived from a single spectrum, obviating the need for a delay scan or a chirped probe pulse.

Purpose To investigate porcine lenses in a lens stretcher with regard to presbyopia corrective procedures. Methods A lens stretching device was designed, which allows to simultaneously determine all relevant geometrical and optical parameters at each stretch position. The setup was used to compare the optical and geometrical lens properties of young slaughter pigs (n = 5) with older sows (n = 7). Results The change of optical power with stretching is about five times larger for young porcine lenses than for sows. For young pigs, the gradient index profile of the crystalline lens significantly contributes to the induced accommodation amplitude. Conclusions We have shown that sow lenses are a suitable model for in vitro experiments on possible treatments for presbyopia. The rapid decrease in the induced accommodation amplitude with age may be explained by a reduced change of all geometrical lens parameters, which in turn leads to a smaller contribution of the gradient index profile to accommodation.

We demonstrate a femtosecond fiber laser system delivering >5-μJ, sub-400-fs pulses at a pulse repetition rate of 200 kHz. At constant average power the pulse repetition rate of this Watt-level femtosecond laser can be adjusted up to several MHz. The laser is monolithically integrated from the oscillator to the booster amplifier stage. The system was applied for structuring metallic as well as transparent media as e.g. biological tissues in ophthalmology.

International audience; Lightning research needs on-demand lightning strikes, because of the random character of natural lightning. Lasers have been proposed as alternatives to the current technique using rocket-pulled wires, because they would expectedly provide more flexibility. However, high-energy, nanosecond lasers cannot provide long connected plasma channels. In contrast, we recently reported the triggering of electric events in thunderclouds using ultrashort laser pulses. Further improvements of the laser pulse sequence and experiment geometry are discussed.

International audience; We investigated the possibility to trigger real-scale lightning using ionized filaments generated by ultrashort laser pulses in the atmosphere. Under conditions of high electric field during two thunderstorms, we observed a statistically significant number of electric events synchronized with the laser pulses, at the location of the filaments. This observation suggests that corona discharges may have been triggered by filaments.

The pharmacokinetics and pharmacodynamics of a single oral dose benazepril.HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19-32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20-40% greater. The elimination half-life of benazeprilat during the first 24 h after dosing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml.min-1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

We show that laser filamentation can be initiated and propagate through strong extended turbulence well above the typical atmospheric values. We suggest that the effect of turbulence on filamentation is characterized by the product of the structure parameter for the refractive index Cn2 and the length L of the turbulence region. Half of the filaments are transmitted for Cn2L⩽4.4×10−10m1∕3. Moreover, the surviving filaments keep their key spectral properties including correlations inside the white-light continuum.

Due to potential of applications, self-trapping of a peak-power laser pulse in a so called filament became an intensively investigated phenomenon. In this paper we demonstrate experimentally advantages of using filaments for the remote laser induced plasma spectroscopy (LIBS). This novel approach can increase effective range of conventional LIBS system up to single kilometers. We also show that Fourier-limited pulse does not optimize LIBS signal, opening the perspective for the pulse shaping techniques in a break-down spectroscopy.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In this paper, ultrashort laser pulses while propagating in air undergo filamentation which results from a dynamic balance between Kerr lens focusing and defocusing on laser-induced micro plasma. Such equilibrium leads to a self-guided ionized channel, or filament, with a diameter on the order of 100 /spl mu/m, extending over long distances up to several hundreds of meters. Using the Teramobile laser system providing 250 mJ pulses of 100 fs duration, centered at 800 nm, we have shown that the beam propagation for multi-TW pulses is driven by the interplay between random nucleation of small-scale cells and relaxation to long waveguides. We compare experimental results with simulations. Also, a white-light supercontinuum is generated by self-phase modulation, and mixing with the generated third harmonic generation (THG) extends the spectrum down to 230 nm in the infrared, providing a promising light source for multiparameter remote sensing by Lidar.

International audience; We demonstrate that the capacity of ultrashort high-power laser pulses to trigger and guide high-voltage discharges can be significantly enhanced by a subsequent visible nanosecond laser pulse. The femtosecond pulse induces a bundle of filaments, which creates a conducting channel of low density and cold plasma connecting the electrodes. The subsequent laser pulse photodetaches electrons from O2- ions in the electrode leader. The resulting electrons allow efficient heating by Joule effect in a retroaction loop, resulting in a 5% reduction of the breakdown voltage.

Fluctuations of the white-light supercontinuum produced by ultrashort laser pulses in selfguided filaments (spatio-temporal solitons) in air are investigated. We demonstrate that correlations exist within the white-light supercontinuum, and that they can be used to significantly reduce the laser intensity noise by filtering the spectrum. More precisely, the fundamental wavelength is anticorrelated with the wings of the continuum, while conjugated wavelength pairs on both sides of the continuum are strongly correlated. Spectral filtering of the continuum reduces the laser intensity noise by 1.2 dB, showing that fluctuations are rejected to the edges of the spectrum., 8 pages

We report experimental and numerical results on supercontinuum generation at ultraviolet/visible wavelengths produced by the long-range propagation of infrared femtosecond laser pulses in air.

International audience; We demonstrate remote elemental analysis at distances up to 90 m, using a laser-induced breakdown spectroscopy scheme based on filamentation induced by the nonlinear propagation of unfocused ultrashort laser pulses. A detailed signal analysis suggests that this technique, remote filament-induced breakdown spectroscopy, can be extended up to the kilometer range.

Optical side-effects of fs-laser treatment in refractive surgery are investigated by means of a model eye. We show that rainbow glare is the predominant perturbation, which can be avoided by randomly distributing laser spots within the lens. For corneal applications such as fs-LASIK, even a regular grid with spot-to-spot distances of ~3 µm is sufficient to minimize rainbow glare perception. Contrast sensitivity is affected, when the lens is treated with large 3D-patterns.

To investigate the pharmacokinetics and the disposition of levoprotiline after i.v. and p.o. administration and to assess the absolute bioavailability, 12 healthy volunteers (11 women, 1 man) were given a 10 min i.v. infusion of 15 mg and a p.o. dose of 75 mg in a two-way crossover study. Blood and urine samples were collected after each dose. Unchanged levoprotiline and the sum of unchanged and glucuronidated levoprotiline (=total levoprotiline) were determined by a specific gas chromatographic-mass spectrometric method. Intravenous levoprotiline was rapidly and extensively distributed into extravascular sites of the body; the steady-state volume of distribution was 18·81 kg−1. The elimination of levoprotiline from blood was independent of the dosing route, the half-life being 18·8h. Only 1·8 and 0·6 per cent of the i.v. and p.o. dose, respectively, were excreted unchanged in the urine, whereas 57 per cent of each dose were renally excreted as total levoprotiline. The absolute bioavailability of p.o. levoprotiline was 40 per cent. About 60 per cent of the dose was subject to a first-pass effect in the liver. The systemic blood clearance of levoprotiline, determined after i.v. dosing, was 885 ml min−1, the renal blood clearance after i.v. and p.o. dosing was only 16·0 and 14·2 ml min−1, respectively. Presystemic and systemic clearance of levoprotiline occurred predominantly by direct glucuronidation.

A specific and sensitive gas chromatographic/mass spectrometric method was developed and validated for the determination of the antidepressant levoprotiline in blood, plasma and urine and the simultaneous determination of levoprotiline and its desmethyl metabolite in urine. Deuterium-labelled analogues were used as internal standards. The compounds were isolated from the biological fluids by liquid-liquid extraction under basic conditions. Following derivatization with perfluoropropionic anhydride, the samples were analysed by capillary column gas chromatography/electron impact mass spectrometry with selected ion monitoring. The analysis of spiked samples demonstrated the high accuracy and precision of the method. Blood concentrations of levoprotiline down to 0.7 nmol l-1 (1 ml used for analysis) could be quantified with a coefficient of variation of 10% or less. The method is suitable for use in pharmacokinetic and bioavailability studies of levoprotiline in humans.

The influence of hepatic disease on the pharmacokinetics of the new ACE inhibitor, benazepril hydrochloride, was evaluated in 12 male patients suffering from liver cirrhosis. The patients received a single oral 20 mg dose. The plasma concentrations and urinary excretion of unchanged benazepril and its active metabolite benazeprilat were determined. Compared with a historical control group of healthy volunteers treated with the same benazepril. HC1 dose, the plasma concentrations of benazepril were doubled in the cirrhotic patients. However, the time to reach maximum concentration (0.5 h) was not affected. The plasma kinetics and the urinary excretion of the metabolite benazeprilat were not significantly altered: Area under the curve and maximum concentration as well as time to maximum concentration (1.5 h) were comparable with those in the healthy subjects. There was also no significant difference between the two populations for the total urinary excretion and the renal clearance of benazeprilat. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 94 per cent, respectively). In conclusion, the rate and the amount of bioactivation of the inactive prodrug benazepril to the active benazeprilat were virtually unaffected by hepatic cirrhosis. Thus, there seems to be no need for dosage adjustment of benazepril hydrochloride in patients suffering from cirrhosis of the liver.

The authors demonstrate optimal control of the propagation of ultrashort, ultraintense (multiterawatt) laser pulses in air over distances up to 36m in a closed-loop scheme. They optimized three spectral ranges within the white-light continuum as well as the ionization efficiency. Optimization results in signal enhancements by typical factors of 2 and 1.4 for the target parameters. The optimization results in shorter pulses by reducing their chirp in the case of white-light continuum generation, while they correct the pulse from its defects and set the filamentation onset near the detector as far as air ionization is concerned.

Mit ultrakurzen Laserpulsen konnen meterlange Plasmen erzeugt werden, die die Luft elektrisch leitend machen. Dies hat zur Idee eines Laser-Blitzableiters gefuhrt.