Quantification of nitroaromatic explosives in contaminated soil using MALDI-TOF mass spectrometry.

Contamination from various sources is a global environmental and health threat, with mining and military activities in particular having spread nitroaromatic compounds, such as 2,4,6-trinitrotoluene and its degradation products and by-products, to the soil. The investigation and monitoring of large contaminated areas requires new detection methods since the established ones are expensive and time-consuming. Hence, we established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method using 1,5-diaminonaphthalene as the matrix substance and an internal standard for quantification. Analyzing standard substances, we found specific signals for radical and fragment ions of different nitrotoluenes and nitrobenzenes with good reproducibility and detection limits down to 0.25 ng/µL. The analysis of soil sample extracts from a former production site showed clear signals for 2,4,6-trinitrotoluene and the primary degradation products aminodinitrotoluenes. Furthermore, quantification gave results comparable to those obtained by conventional liquid chromatography-tandem mass spectrometry analysis. The MALDI-TOF MS method has a comparatively lower reproducibility, with relative standard deviations of 6% to 20% for multiple measurements of standard solutions and soil sample extracts. Nevertheless, a comparison of both methods revealed the advantages of MALDI-TOF MS analysis of explosive-contaminated areas with regard to costs, time, and handling. Finally, our MALDI-TOF MS method fulfills all the needs for high sample throughput and can therefore be a valuable screening tool for explosive-contaminated areas. Graphical abstract.

Brain volumetry and self-regulation of brain activity relevant for neurofeedback.

Neurofeedback is a technique to learn to control brain signals by means of real time feedback. In the present study, the individual ability to learn two EEG neurofeedback protocols - sensorimotor rhythm and gamma rhythm - was related to structural properties of the brain. The volumes in the anterior insula bilaterally, left thalamus, right frontal operculum, right putamen, right middle frontal gyrus, and right lingual gyrus predicted the outcomes of sensorimotor rhythm training. Gray matter volumes in the supplementary motor area and left middle frontal gyrus predicted the outcomes of gamma rhythm training. These findings combined with further evidence from the literature are compatible with the existence of a more general self-control network, which through self-referential and self-control processes regulates neurofeedback learning.

Changes in hemodynamic signals accompanying motor imagery and motor execution of swallowing: a near-infrared spectroscopy study.

In the present study we investigated hemodynamic changes in the brain in response to motor execution (ME) and motor imagery (MI) of swallowing using near-infrared spectroscopy (NIRS). Previous studies provide evidence that ME and MI of limb movements lead to comparable brain activation patterns indicating the potential value of MI for motor rehabilitation. In this context, identifying brain correlates of MI of swallowing may be potentially useful for the treatment of dysphagia. Fourteen healthy participants actively swallowed water (ME) and mentally imagined to swallow water (MI) in a randomized order while changes in concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) were assessed. MI and ME led to the strongest NIRS signal changes in the inferior frontal gyrus. During and after ME, oxy-Hb significantly increased, with a maximum peak around 15s after task onset. In contrast, oxy-Hb decreased during MI compared to a rest period probably because of motor inhibition mechanisms. Changes in deoxy-Hb were largely comparable between MI and ME, especially when participants used a kinesthetic motor imagery strategy during MI compared to no specific strategy. Hence, the present study provides new evidence concerning timing and topographical distribution of the hemodynamic response during ME and MI of swallowing.

Near-infrared spectroscopy based neurofeedback training increases specific motor imagery related cortical activation compared to sham feedback.

In the present study we implemented a real-time feedback system based on multichannel near-infrared spectroscopy (NIRS). Prior studies indicated that NIRS-based neurofeedback can enhance motor imagery related cortical activation. To specify these prior results and to confirm the efficacy of NIRS-based neurofeedback, we examined changes in blood oxygenation level collected in eight training sessions. One group got real feedback about their own brain activity (N=9) and one group saw a playback of another person's feedback recording (N=8). All participants performed motor imagery of a right hand movement. Real neurofeedback induced specific and focused brain activation over left motor areas. This focal brain activation became even more specific over the eight training sessions. In contrast, sham feedback led to diffuse brain activation patterns over the whole cortex. These findings can be useful when training patients with focal brain lesions to increase activity of specific brain areas for rehabilitation purpose.

Advanced methods for time-varying effective connectivity estimation in memory processes.

Memory processes are based on large cortical networks characterized by non-stationary properties and time scales which represent a limitation to the traditional connectivity estimation methods. The recent development of connectivity approaches able to consistently describe the temporal evolution of large dimension connectivity networks, in a fully multivariate way, represents a tool that can be used to extract novel information about the processes at the basis of memory functions. In this paper, we applied such advanced approach in combination with the use of state-of-the-art graph theory indexes, computed on the connectivity networks estimated from high density electroencephalographic (EEG) data recorded in a group of healthy adults during the Sternberg Task. The results show how this approach is able to return a characterization of the main phases of the investigated memory task which is also sensitive to the increased length of the numerical string to be memorized.

Non-steady-state photoelectromotive force effect under linear and periodical phase modulation: application to detection of Doppler frequency shift.

Non-steady-state photoelectromotive force effect in the presence of periodical and linear phase shift was investigated both theoretically and experimentally. It was shown that superposition of oscillating and linear movements of the interference pattern leads to the appearance of the sharp peak in the frequency dependence of the photoelectromotive force output current when the frequency of periodical modulation matches the frequency of the linear phase shift. We demonstrated experimentally that this effect can be used for determination of a Doppler frequency shift between signal and reference beam.

Three-dimensional holographic imaging of living tissue using a highly sensitive photorefractive polymer device.

Photorefractive materials are dynamic holographic storage media that are highly sensitive to coherent light fields and relatively insensitive to a uniform light background. This can be exploited to effectively separate ballistic light from multiply-scattered light when imaging through turbid media. We developed a highly sensitive photorefractive polymer composite and incorporated it into a holographic optical coherence imaging system. This approach combines the advantages of coherence-domain imaging with the benefits of holography to form a high-speed wide-field imaging technique. By using coherence-gated holography, image-bearing ballistic light can be captured in real-time without computed tomography. We analyzed the implications of Fourier-domain and image-domain holography on the field of view and image resolution for a transmission recording geometry, and demonstrate holographic depth-resolved imaging of tumor spheroids with 12 microm axial and 10 microm lateral resolution, achieving a data acquisition speed of 8 x 10(5) voxels/s.

Rate-limiting biotransformation of triamterene is mediated by CYP1A2.

OBJECTIVE: Triamterene (TA), a potassium-sparing diuretic, is extensively metabolized by hydroxylation in 4'-position and subsequent conjugation by cytosolic sulfotransferases. To identify the cytochrome P450 enzyme(s) catalyzing hydroxylation of triamterene (the rate-limiting step in the formation of the sulfate ester (STA)), in vitro incubation studies were performed with human liver microsomes. METHODS: Initial rates of TA hydroxylation (0 - 300 microM) were determined during a ten-minute-incubation period with liver microsomes of two donors. The role of individual CYP enzymes was determined by pre-incubation with selective inhibitors/alternative substrates. Vice versa, the effect of TA (0 - 500 microM) on 3-demethylation of caffeine (0 - 1,000 microM) was assessed. Metabolite concentrations were estimated by reversed-phase HPLC methods. RESULTS: TA Km values without inhibitors were 60 and 142 microM, Vmax was 177 and 220 pmol/min/mg protein, respectively. Mean inhibitor induced changes of 4'-hydroxy-TA formation were as follows: Furafylline 25 microM (CYP1A2), complete inhibition (-100%); omeprazole 250 microM (CYP1A2 inhibitor/CYP2C 19 substrate), -30%; coumarin 25 microM (CYP2A6), -11%; quinidine 25 microM (CYP2D6), -9%; ketoconazole 25 microM (CYP3A), -18%; and erythromycin 250 microM (CYP3A), -8%. In the reverse inhibition studies, TA competitively inhibited caffeine 3-demethylation with Ki values of 65 and 111 microM, respectively. CONCLUSION: 4'-hydroxylation of TA in humans appears to be mediated exclusively by CYP1A2. Inhibition or induction of CYP1A2 will change the time course of both TA and its active phase-II metabolite. The net pharmacodynamic effect of such changes is difficult to predict and needs to be evaluated in clinical studies.

Time course and extent of angiotensin II antagonism after irbesartan, losartan, and valsartan in humans assessed by angiotensin II dose response and radioligand receptor assay.

OBJECTIVES: To compare the angiotensin II antagonistic properties of the usual recommended oral starting doses of various angiotensin II receptor antagonists-150 mg irbesartan, 80 mg valsartan, and 50 mg losartan-in humans. SUBJECTS AND METHODS: Eighteen healthy men were enrolled in a double-blind, randomized crossover study. Angiotensin II dose-effect curves of diastolic blood pressure and radioreceptor assay were performed before and up to 47 hours after single and multiple doses of the antagonists. The rightward shift of the angiotensin II dose-effect curves (dose ratio-1) assessed the antagonistic effects in vivo. The degree of receptor occupancy in plasma was detected by a rat lung radioreceptor assay ex vivo in vitro. RESULTS: All of the drugs clearly showed antagonistic effects to angiotensin II in vivo (dose ratio-1) and in vitro (radioreceptor assay). Within the given doses the dose ratio-1 for irbesartan was greater than for valsartan and losartan after single and repetitive dosing, reaching statistical significance at various time points up to 36 hours versus valsartan and up to 47 hours versus losartan. The apparent half-lives of the decay of the effects were approximately 8 hours for valsartan and losartan, whereas 15 to 18 hours were obtained with irbesartan. These findings were supported by the radioreceptor assay data: the percentage of receptor occupancy for irbesartan was significantly greater than for valsartan and losartan up to 47 hours. CONCLUSION: Angiotensin II antagonistic effects of irbesartan, valsartan, and losartan were compared. Irbesartan showed the slowest decay and longest duration of its antagonistic effects. With the recommended initial doses used in this study, the following rank order of antagonistic intensity was obtained: irbesartan > valsartan > losartan. The findings of this study, specifically the longer-lasting effects of irbesartan, may have clinical implications.

Oxygen transport during hemodilution in normoxic and hypoxic dogs treated with verapamil.

In order to determine the possible limitations of acute isovolemic hemodilution in patients taking verapamil, the various factors determining oxygen availability were analyzed in an animal experiment. Twenty-four anaesthetized dogs were subjected to a gradual isovolemic hemodilution. Six dogs received a bolus injection of 0.1 mg kg-1 of verapamil followed by 0.01 mg kg-1 min-1. In 12 dogs, mild hypoxic hypoxia was induced by ventilation with 16-17% oxygen; six of them also received verapamil. Six dogs served as a control group. In the latter, due to an increase in heart rate and stroke volume, oxygen availability in the clinically relevant range of hemodilution between HC 25 and 25% was maintained at 81% of its control value. In normoxic animals treated with verapamil, oxygen availability decreased more rapidly and was below the level of the control group once HC reached 25%. Mild hypoxic hypoxia alone did not reduce oxygen availability as much as its combination with verapamil. Even though the verapamil-induced reduction in oxygen availability was similar during normoxia and hypoxia, the sharp rise in serum lactate at HC levels below 35-30% in the hypoxic verapamil group was a sign of impairment of tissue oxygenation. Hematocrit levels below 35-30% and even moderate hypoxemia should be avoided whenever the cardiovascular response to hemodilution is influenced by verapamil.