Assessment of flow-mediated dilatation in the superficial femoral artery using a sustained shear stress stimulus via calf plantar-flexion exercise.

NEW FINDINGS: What is the central question of this study? The aim was to establish the ability of a newly designed leg exercise technique to produce sustained elevations in shear rate that stimulate flow-mediated dilatation (FMD) in the superficial femoral artery and to determine the repeat trial stability of the FMD response. What is the main finding and its importance? Calf plantar-flexion exercise can be used to increase shear stress and stimulate FMD in the superficial femoral artery. However, the magnitude of FMD varied systematically when multiple trials were repeated in short succession. The superficial femoral artery (SFA) is susceptible to vascular disease, and a technique to assess flow-mediated dilatation (FMD) in this vessel in response to a sustained shear stress stimulus could provide important information about endothelial function. The aim of this study was to establish the ability of a newly designed SFA leg exercise-FMD (LEX-FMD) technique to produce sustained elevations in shear rate, which stimulate FMD, and to determine the repeat trial stability of the FMD response. The SFA FMD stimulated by reactive hyperaemia (RH) and calf plantar-flexion exercise (LEX) was assessed via ultrasound in 19 healthy men (n = 10) and women (n = 9). The two experimental visits included either four trials of LEX-FMD or four trials of RH-FMD. The shear stress stimulus was estimated as the shear rate (blood velocity/SFA diameter). Results are expressed as the means ± SD. The LEX steady-state shear rate was consistent between trials (P = 0.176), whereas the RH shear rate area under the curve was higher in trial 1 versus trials 2-4 (P < 0.05). The %RH-FMD (four-trial mean 4.9 ± 2.5%) and absolute RH-FMD were not significantly different between trials (P = 0.465 and P = 0.359, respectively). Both %LEX-FMD and absolute LEX-FMD were higher during trial 3 (4.8 ± 3.4%) than trial 1 (3.6 ± 2.7%; P = 0.026 and P = 0.026, respectively). The magnitude of RH-FMD and LEX-FMD did not differ (P = 0.241). These results indicate that calf plantar-flexion exercise can be used to increase shear stress and stimulate FMD in the SFA. However, although SFA RH-FMD was stable across four trials, LEX-FMD varied systematically when multiple trials were repeated in rapid succession.

Escalation of methamphetamine-related crime and fatalities in the Dresden region, Germany, between 2005 and 2011.

Methamphetamine (MA), a central nervous system stimulating recreational drug, is a worldwide problem related to crime as well as forensic and health aspects. The data, exemplarily presented in this study for the Dresden region, Saxony, Germany, demonstrate the escalation of MA-related crime and fatalities between 2005 and 2011. Easy availability and an attractive price of MA in the Czech Republic are responsible for both the increase of the occurrence of MA in relation to the entire drug crime as well as the increase of the occurrence of MA-positive cases of driving under influence (DUI). Higher percentage of very pure MA on the Saxon drug market since 2010 seems to be the reason for the fatalities directly caused by MA in 2010 and 2011.

Simultaneous bilateral hip joint imaging at 7 Tesla using fast transmit B1 shimming methods and multichannel transmission - a feasibility study.

The objective of this study was to demonstrate the feasibility of simultaneous bilateral hip imaging at 7 Tesla. Hip joint MRI becomes clinically critical since recent advances have made hip arthroscopy an efficacious approach to treat a variety of early hip diseases. The success of these treatments requires a reliable and accurate diagnosis of intraarticular abnormalities at an early stage. Articular cartilage assessment is especially important to guide surgical decisions but is difficult to achieve with current MR methods. Because of gains in tissue contrast and spatial resolution reported at ultra high magnetic fields, there are strong expectations that imaging the hip joint at 7 Tesla will improve diagnostic accuracy. Furthermore, there is growing evidence that the majority of these hip abnormalities occur bilaterally, emphasizing the need for bilateral imaging. However, obtaining high quality images in the human torso, in particular of both hips simultaneously, must overcome a major challenge arising from the damped traveling wave behaviour of RF waves at 7 Tesla that leads to severe inhomogeneities in transmit B1 (B(1) (+) ) phase and magnitude, typically resulting in areas of low signal and contrast, and consequently impairing use for clinical applications. To overcome this problem, a 16-channel stripline transceiver RF coil was used, together with a B1 shimming algorithm aiming at maximizing B(1) (+) in six regions of interest over the hips that were identified on axial scout images. Our successful results demonstrate that this approach effectively reduces inhomogeneities observed before B1 shimming and provides high joint tissue contrast in both hips while reducing the required RF power. Critical to this success was a fast small flip angle B(1) (+) calibration scan that permitted the computation of subject-specific B1 shimming solutions, a necessary step to account for large spatial variations in B(1) (+) phase observed in different subjects.

Acoustic noise-optimized VERSE pulses.

Variable-rate selective excitation RF pulses modulate the slice selection gradients during RF transmission, especially to reduce the total RF power. Amplitude-modulated slice selection gradients can lead to increased gradient noise, in particular in high-field MRI where variable-rate selective excitation techniques are often used. In this work, an algorithm is presented that calculates a variable-rate selective excitation pulse modulation from given RF pulses with constant slice selection gradient. The algorithm avoids the known acoustic resonance frequencies of the gradient system to minimize sound pressure levels. It was tested with four different slice-selective RF pulse shapes (Sinc, Gaussian, and two Shinnar-LeRoux). Sound measurements revealed a reduction of the mean sound pressure level by up to 13 dB, and simultaneously, the specific absorption rate was reduced by 55%.

Silent echo-planar imaging for auditory FMRI.

INTRODUCTION: The effect of the acoustic scanner noise produced by gradient coil switching on the auditory evoked BOLD signal represents a well-known problem in auditory functional MRI (FMRI). In this paper, a new low-noise echo-planar imaging (EPI) sequence is presented that is optimized for auditory FMRI measurements. METHODS: The sequence produces a narrow-band acoustic frequency spectrum by using a sinusoidal readout echo train and a constant phase encoding gradient. This narrow band is adapted to the frequency response function of the MR scanner by varying the switching frequency of the sinusoidal readout gradient. RESULTS: Compared to a manufacturer-provided standard EPI sequence, the acoustic noise reduction amounts to up to 20 dBA. Using a simple block design paradigm contrasting presentation of a pure tone during ON blocks and "silence" (absence of the tone) during OFF blocks, the new low-noise sequence was evaluated and compared to the standard EPI sequence. Statistical parametric mapping (SPM) resulted in higher levels of significance of auditory activation for the low-noise sequence. DISCUSSION: These findings strongly suggest that the low-noise sequence may generate enhanced BOLD contrasts compared to the standard EPI sequences commonly used in FMRI.

Novel design of a compact "cylindrical mirror analyzer" array.

The design of a compact multiangle electron analyzer array for simultaneous detection of scattered and ejected electrons at nine different angles is described. It consists of eight slim "simulated" cylindrical mirror analyzers (CMAs) providing electron detection for scattering/ejected angles of 14 degrees apart from each other. A ninth analyzer is arranged to a scattering angle on the opposite side. A single analyzer has cylindrical symmetry equipotential lines in the region of the beam trajectories, whereas its electrodes are noncylindrical, except for the inner cylinder. The new spectrometer is easy to build because only a few electrodes of simple shape are needed for each of the analyzers. The electron optical properties of the new device are very close to those of a true CMA. Its geometric width, however, is only less than one-fifth of that of a conventional CMA, which allows one to arrange several analyzers close to each other. Example results with the new device are presented.

Bilirubin toxicity and differentiation of cultured astrocytes.

OBJECTIVE: To study the toxicity of bilirubin in primary cultures of newborn rat cerebral cortical astrocytes. STUDY DESIGN: Primary cultures of newborn rat astrocytes were incubated at bilirubin concentrations of 0, 1, 5, 10, 25, 50, 100, 200, and 2000 microM, at a bilirubin:albumin molar ratio of 1.7. Bilirubin toxicity was determined by changes in cellular morphology, trypan blue staining, and lactate dehydrogenase (LDH) release into the culture medium at various times of incubation. To determine if differentiation of astrocytes affects bilirubin toxicity, cultures were treated with dibutyryl cyclic adenosine monophosphate. RESULTS: All three indices of toxicity showed a bilirubin concentration dependence. LDH release in experimental cultures was significantly elevated (p < 0.05) above that of control cultures by 24 hours at bilirubin concentrations of > or = 100 microM. The absolute amount of LDH release differed significantly between the 200 and 2000 microM cultures from 1.5 to 24 hours, after which duration of exposure appeared to take over and all cultures approached maximum. LDH release for the lower concentrations all reached maximum by 120 hours, except for the 1 microM cultures, which showed no significant elevation above control throughout the study period. At 100 and 200 microM bilirubin, LDH release by untreated cells was significantly higher (p < 0.05) than release by treated cells by 36 hours. CONCLUSION: Undifferentiated astrocytes appeared to be more sensitive to bilirubin toxicity, which may correlate with the greater susceptibility of newborns to kernicteric injury. Studies with primary astrocyte culture may provide insight into how bilirubin sensitivity changes with brain development as well as the cellular and biochemical mechanisms of bilirubin encephalopathy.

Substitution of aromatic and nonaromatic amino acids for the Phe3 residue in the delta-selective opioid peptide deltorphin I: effects on binding affinity and selectivity.

Deltorphins I and II (Tyr-D-Ala-Phe-Asp-Val-Val-Gly NH2 and Tyr-D-Ala-Phe-Glu-Val-Val-Gly NH2) display a high degree of delta-opioid receptor selectivity. Since they lack the intervening Gly3 residue found between the Tyr and Phe aromatic moieties in pentapeptide enkephalins, deltorphins I and II resemble a previously described series of cyclic tetrapeptides based on Tyr-c[D-Cys-Phe-D-Pen] (JOM-13). With the goal of development of structure-activity relationships for deltorphins and comparison with that of the cyclic tetrapeptides, ten analogs of deltorphin I were synthesized in which Phe3 was replaced with specific aromatic and nonaromatic amino acids with varying physicochemical properties. Results indicated that analogs containing the bicyclic aromatic amino acids 3-(1-naphthyl)-L-alanine [1-Nal; Ki(mu) = 767 nM, Ki(delta) = 7.70 nM], 3-(2-naphthyl)-L-alanine [2-Nal; Ki(mu) = 1910 nM, Ki(delta) = 49.2 nM], tryptophan [Ki(mu) = 1250 nM, Ki(delta) = 23.9 nM], and 3-(3-benzothienyl)-L-alanine [Bth; Ki(mu) = 112 nM, Ki(delta) = 3.36 nM] were fairly well tolerated at mu- and delta-receptors, though affinity was compromised to varying degrees relative to deltorphin I. Shortening the Phe side chain by incorporation of phenylglycine (Pgl) was detrimental to both mu (Ki = 4710 nM) and delta (Ki = 15.6 nM) binding, while extension of the side chain with homophenylalanine (Hfe) enhanced mu binding (Ki = 67.8 nM), leaving delta affinity unaffected (Ki = 2.64 nM). Substitution with nonaromatic amino acids valine and isoleucine led expectedly to poor opioid binding [Ki(mu) = > or = 10,000 nM for each, Ki(delta) = 160 and 94.7 nM, respectively], while peptides containing cyclohexylalanine (Cha) and leucine surprisingly retained affinity at both mu (Ki = 322 and 1240 nM, respectively) and delta (Ki = 10.5 and 12.4 nM, respectively) sites. In general, these trends mirror those observed for similar modification in Tyr-c[D-Cys-Phe-D-Pen].