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1H‐magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single‐voxel MRS (point‐resolved single‐voxel spectroscopy sequence, 1.5 T: echo time [TE] 23–37 ms/135–144 ms, repetition time [TR] 1500 ms; 3 T: TE 37–41 ms/135–144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann–Whitney U‐tests and Kruskal–Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours. [ABSTRACT FROM AUTHOR]

Continued increases in nitrogen and phosphorus loads in waterways cause problems with water quality, impacting human health, the economy, and the environment. To reach nutrient load reduction targets, innovative conservation strategies should be evaluated. This study used oval mesocosms (1.2 m × 0.58 m × 0.58 m) to assess the (1) potential of using woodchip‐bioditch reactors for the mitigation of nitrate (NO3−) and soluble reactive phosphorus (SRP) in agricultural waterways; (2) influence of bioditch reactor orientation (parallel, perpendicular, and hybrid) to flow direction on NO3− and SRP concentrations and loads; and (3) impact of bioditch reactor saturation (dry, intermittently wet, and wet) on NO3− and SRP loads reduction. Woodchip‐bioditch reactors successfully reduced NO3− loads compared to controls (p ⩽ 0.031), but SRP load was sometimes higher in bioditch reactor treatments. No consistent differences were identified between orientation of bioditch reactors and flow direction. The constantly wet treatment had a significantly higher NO3− load reduction than the dry treatment and control (p ⩽ 0.042). Our results indicate the promise of woodchip‐bioditch reactors as a nutrient reduction conservation strategy, although further study of nutrient and greenhouse gas dynamics is needed before widespread implementation. Core Ideas: Woodchip bioreactors can reduce nutrients in runoff.Bioditch reactor placement in differing orientations to ditch flow can slow nutrient loss.Constantly wet bioditch reactors reduce more nitrate than dry or intermittently wet bioreactors.Bioditch reactors could provide a flexible option for agricultural runoff nutrient mitigation. [ABSTRACT FROM AUTHOR]

Purpose To estimate the exchange rates of labile 1H in citrate and spermine, metabolites present in prostatic secretions, to predict the size of the citrate and spermine CEST effects in vivo. Methods CEST z-spectra were acquired at high-field [11.7 Tesla (T)] from citrate and spermine solutions at physiological pH (6.5) using saturation power 6 μT. CEST was performed at different temperatures to determine exchange regimes (slow, intermediate or fast). For low pH solutions of spermine, exchange rates were estimated from resonance line width, fitting z-spectra using the Bloch equations incorporating exchange, and using quantifying exchange using saturation time experiments (QUEST). These rates were extrapolated to physiological pH. Results Citrate showed little CEST effect at pH 6.5 and temperature (T) = 310 K (maximum 0.001% mM-1), indicating fast exchange, whereas spermine showed greater CEST effects (maximum 0.2% mM-1) indicating intermediate-to-fast exchange. Extrapolating data acquired from low pH spermine solutions predicts exchange rates at pH 6.5 and T of 310 K of at least 2 × 104s-1. Conclusion Citrate and spermine show minimal CEST effects at 11.7T even using high saturation power. These effects would be much less than 2% at clinical field-strengths due to relatively faster exchange and would be masked by CEST from proteins. Magn Reson Med 76:742-746, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical utility of the reverse gradient algorithm in correcting distortions in diffusion-weighted images of the cervix and for increasing diagnostic performance.Materials and Methods: Forty-one patients ages 25-72 years (mean 40 ± 11 years) with suspected or early stage cervical cancer were imaged at 3T using an endovaginal coil. T2 -weighted (W) and diffusion-weighted images with right and left phase-encode gradient directions were obtained coronal to the cervix (b = 0, 100, 300, 500, 800 s mm(-2) ). Differences in angle of the endocervical canal to the x-axis between T2 W and right-gradient, left-gradient, and corrected images were measured. Uncorrected and corrected images were assessed for diagnostic performance when viewed together with T2 W images by two independent observers against subsequent histology.Results: The angles of the endocervical canal relative to the x-axis were significantly different between the T2 W images and the right-gradient images (P = 0.007), approached significance for left-gradient images (P = 0.055), and were not significantly different after correction (P = 0.95). Corrected images enabled a definitive diagnosis in 34% (n = 14) of patients classified as equivocal on uncorrected images. Tumor volume in this subset was 0.18 ± 0.44 cm(3) (mean ± SD; sensitivity of detection 100% [8/8], specificity 50% [3/6] for an experienced observer). Correction did not improve diagnostic performance for the less-experienced observer.Conclusion: Distortion-corrected diffusion-weighted images improved correspondence with T2 W images and diagnostic performance in a third of cases. [ABSTRACT FROM AUTHOR]

Purpose: To compare the depiction of metabolite signals in short and long echo time (TE) prostate cancer spectra at 3T, and to quantify their concentrations in tumors of different stage and grade, and tissues adjacent to tumor.Materials and Methods: First, single-voxel magnetic resonance imaging (MRI) spectra were acquired from voxels consisting entirely of tumor, as defined on T2-weighted and diffusion-weighted (DW)-MRI and from a biopsy-positive octant, at TEs of 32 msec and 100 msec in 26 prostate cancer patients. Then, in a separate cohort of 26 patients, single-voxel TE = 32 msec MR spectroscopy (MRS) was performed over a partial-tumor region and a matching, contralateral normal-appearing region, defined similarly. Metabolite depiction was compared between TEs using Cramér-Rao lower bounds (CRLB), and absolute metabolite concentrations were calculated from TE = 32 msec spectra referenced to unsuppressed water spectra.Results: Citrate and spermine resonances in tumor were better depicted (had significantly lower CRLB) at TE = 32 msec, while the choline resonance was better depicted at TE = 100 msec. Citrate and spermine concentrations were significantly lower in patients of more advanced stage, significantly lower in Gleason grade 3+4 than 3+3 tumors, and significantly lower than expected from the tumor fraction in partial-tumor voxels (by 14 mM and 4 mM, respectively, P < 0.05).Conclusion: Citrate and spermine resonances are better depicted at short TE than long TE in tumors. Reduction in these concentrations is related to increasing tumor stage and grade in vivo, while reductions in the normal-appearing tissues immediately adjacent to tumor likely reflect tumor field effects. [ABSTRACT FROM AUTHOR]

Measurement of tissue lactate using 1H MRS is often confounded by overlap with intense lipid signals at 1.3 ppm. Single-voxel localization using PRESS is also compromised by the large chemical shift displacement between voxels for the 4.1 ppm (-CH) resonance and the 1.3 ppm -CH3 resonance, leading to subvoxels with signals of opposite phase and hence partial signal cancellation. To reduce the chemical shift displacement to negligible proportions, a modified semi-LASER sequence was written ('FOCI-LASER', abbreviated as fLASER) using FOCI pulses to permit high RF bandwidth even with the limited RF amplitude characteristic of clinical MRI scanners. A further modification, MQF-fLASER, includes a selective multiple-quantum filter to detect lactate and reject lipid signals. The sequences were implemented on a Philips 3 T Achieva TX system. In a solution of brain metabolites fLASER lactate signals were 2.7 times those of PRESS. MQF-fLASER lactate was 47% of fLASER (the theoretical maximum is 50%) but still larger than PRESS lactate. In oil, the main 1.3 ppm lipid peak was suppressed to less than 1%. Enhanced suppression was possible using increased gradient durations. The minimum detectable lactate concentration was approximately 0.5 mM. Coherence selection gradients needed to be at the magic angle to avoid large water signals derived from intermolecular multiple-quantum coherences. In pilot patient measurements, lactate peaks were often observed in brain tumours, but not in cervix tumours; lipids were effectively suppressed. In summary, compared with PRESS, the fLASER sequence yields greatly superior sensitivity for direct detection of lactate (and equivalent sensitivity for other metabolites), while the single-voxel single-shot MQF-fLASER sequence surpasses PRESS for lactate detection while eliminating substantial signals from lipids. This sequence will increase the potential for in vivo lactate measurement as a biomarker in targeted anti-cancer treatments as well as in measurements of tissue hypoxia. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Back-to-back 1H MRSI scans, using an endorectal and phased-array coil combination, were performed on 18 low-risk patients with prostate cancer at 3 T, employing TEs of 32 and 100 ms in order to compare metabolite visualization at each TE. Outer-volume suppression of lipid signals was performed using regional saturation (REST) slabs and the quantification of spectra at both TEs was achieved with the quantitation using quantum estimation (QUEST) routine. Metabolite nulling experiments in an additional five patients found that there were negligible macromolecule background signals in prostate spectra at TE = 32 ms. Metabolite visibility was judged using the criterion Cramér-Rao lower bound (CRLB)/amplitude < 20%, and metabolite concentrations were corrected for relaxation effects and referenced to the data acquired in corresponding water-unsuppressed MRSI scans. For the first time, the prostate metabolites spermine and myo-inositol were quantified individually in vivo, together with citrate, choline and creatine. All five metabolite visibilities were higher in TE = 32 ms MRSI than in TE = 100 ms MRSI. At TE = 32 ms, citrate was visible in 99.0% of lipid-free spectra, whereas, at TE = 100 ms, no metabolite simulation of citrate matched the in vivo peaks. Spermine, choline and creatine were visualised separately in 30.4% more spectra at TE = 32 ms than at TE = 100 ms, and myo-inositol in 72.5% more spectra. T2 values were calculated for spermine (53 ± 16 ms), choline (62 ± 17 ms) and myo-inositol (90 ± 48 ms). Data from the TE = 32 ms spectra showed that the concentrations of citrate and spermine secretions were positively correlated in both the peripheral zone and central gland ( R2 = 0.73 and R2 = 0.43, respectively), and that the citrate content was significantly higher in the former at 64 ± 22 m m than in the latter at 32 ± 16 m m ( p = 0.01). However, lipid contamination at TE = 32 ms was substantial; therefore, to make clinical use of the greater visualisation of prostate metabolites at TE = 32 ms rather than at TE = 100 ms, three-dimensional MRSI at TE = 32 ms with effective lipid suppression must be implemented. ©2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

31P magnetic resonance spectroscopy (31P MRS) can measure intracellular pH (pHi) using the chemical shift difference between pH-dependent inorganic phosphate (Pi) and a pH-independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using 1H MRS)] in a cohort of 10 volunteers and eight patients with non-Hodgkin's lymphoma (NHL). Well-resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct Pi-PCr method was best for those spectra with a very well-defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the Pi-αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water-based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the Pi-αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment-related changes of the order of 0.1 pH units should be detectable. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study aimed to characterize changes in lipid saturation using magnetic resonance spectroscopy of sensitive (HeLa) and resistant (C33A; Me180) cervical cancer cell lines following exposure to paclitaxel to explore lipid profiles as biomarkers of drug resistance. Spectra were acquired at 11.74 T. Flow cytometry, electron, and confocal microscopy assessed cellular morphology. Western blots assessed cytoplasmic phospholipase A2, fatty acid synthase, and acyl-CoA synthetase1 expression. After 24 h of paclitaxel exposure, >60% of cells showed mitotic arrest. At 48 h, HeLa cells showed apoptosis while C33A/Me180 cells showed normal morphology indicating resistance. MR-visible lipids increased significantly in all lines at 24 h with further increases at 48 h; resistant lines showed smaller increases than HeLa. Cytoplasmic phospholipase A2 and fatty acid synthase levels were unchanged at 24 h and dropped at 48 h in HeLa; acyl-CoA synthetase1 was higher in Me180/C33A than in HeLa controls but did not increase significantly. The percentage of cells displaying lipid droplets increased significantly at 24 and 48 h in all lines; droplet size increased only in HeLa cells. Droplet number was >3-4× greater in apoptotic compared with mitotic-arrested cells. Apoptotic cells accumulate unsaturated fatty acids in large (relative to control) droplets; resistant lines accumulated smaller droplets with less triglycerides. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the effect of experimental conditions on the visibility of polyamines. In solution the chemical shift of the three groups of peaks (at approximately 1.8, 2.1 and 3.1 ppm) were found to be pH dependent. Relaxation times in aqueous solution at pH 7.0, 298 K and 11.74 T were measured to be: putrescine (T1 = 2.49 s, T2 = 2.07 s), spermidine (T1 = 1.27 s, T2 = 1.05 s) and spermine (T1 = 1.02 s, T2 = 0.82 s). Simple spin-echo sequences could not be used to measure T2 as the spins also experience phase evolution from homonuclear coupling which imposes a modulation on the T2 decay curve. This modulation is eliminated by using CPMG sequences with an echo spacing of <500 µs. Relaxation times for spermine in solution in presence of metal ions and protein showed that metal ions had little effect on T2; however, addition of 15 mg/ml bovine serum albumin reduced T2 of spermine (0.41 s at 298 K and 0.19 s at 277 K) but was not as short as the T2 of the polyamine peak in prostatic tissue (0.03 s at 277 K). The MR visibility of polyamines in prostate cell extracts, PC-3 xenograft (intact as well as extracted) and intact human prostatic tissues were investigated. Polyamines were not detected in methanol/chloroform extracts, but were visible in perchloric acid extracts of prostate tumour cells. No polyamines were detected in the HR MAS spectra of three samples of whole PC-3 xenograft tissue studied. In summary, the chemical shift of polyamine species is pH dependent, while protein binding causes peak broadening and reduction in T2. Perchloric acid extraction improves visibility of intracellular polyamines, but whole tissue polyamines are not seen in xenografts without epithelial/ ductal structure. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Carboxypeptidase G2 (CPG2) is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene-directed enzyme prodrug therapy (GDEPT). Employing dynamic nuclear polarization (DNP) and natural abundance 13C magnetic resonance spectroscopy (MRS), we observed the CPG2-mediated conversion of a novel hyperpolarized reporter probe 3,5-difluorobenzoyl-L-glutamic acid (3,5-DFBGlu) to 3,5-difluorobenzoic acid (3,5-DFBA) and L-glutamic acid (L-Glu) in vitro. Isotopic labeling of the relevant nuclei with 13C in 3,5-DFBGlu or related substrates will yield a further factor of 100 increase in the signal-to-noise. We discuss the feasibility of translating these experiments to generate metabolic images of CPG2 activity in vivo. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Development and evaluation of new anticancer drugs are expedited when minimally invasive biomarkers of pharmacokinetic and pharmacodynamic behaviour are available. Gene-directed enzyme prodrug therapy (GDEPT) is a suicide gene therapy in which the anticancer drug is activated in the tumor by an exogenous enzyme previously targeted by a vector carrying the gene. GDEPT has been evaluated in various clinical trials using several enzyme/prodrug combinations. The key processes to be monitored in GDEPT are gene delivery and expression, as well as prodrug delivery and activation. {4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl}-L-glutamic acid, a prodrug for the GDEPT enzyme carboxypeptidase-G2 (CPG2; Km = 1.71 µM; kcat = 732 s−1), was measured with 19F magnetic resonance spectroscopy (MRS). The 1 ppm chemical shift separation found between the signals of prodrug and activated drug (4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoic acid) is sufficient for the detection of prodrug activation in vivo. However, these compounds hydrolyze rapidly, and protein binding broadens the MR signals. A new CPG2 substrate was designed with hydroxyethyl instead of chloroethyl groups ( Km = 3.5 µM, kcat = 747 s−1). This substrate is nontoxic and stable in solution, has a narrow MRS resonance in the presence of bovine and foetal bovine albumin, and exhibits a 1.1 ppm change in chemical shift upon cleavage by CPG2. In cells transfected to express CPG2 in the cytoplasm (MDA MB 361 breast carcinoma cells and WiDr colon cancer cells), well-resolved 19F MRS signals were observed from clinically relevant concentrations of the new substrate and its nontoxic product. The MRS conversion half-life (470 min) agreed with that measured by HPLC (500 min). This substrate is, therefore, suitable for evaluating gene delivery and expression prior to administration of the therapeutic agent. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Choline metabolites are widely studied in cancer research as biomarkers of malignancy and as indicators of therapeutic response. However, endogenous phosphocholine levels are determined by a number of processes that confound the interpretation of these measurements, including membrane transport rates and a series of enzyme catalysed reactions in the Kennedy pathway. Employing a dynamic 31P NMR assay that is specific to choline kinase (ChoK) we have measured the rates of this enzyme reaction in cell lysates of MDA-MB-231 breast, PC-3 prostate and HeLa cervical cancer cells and in solutions of purified human ChoK. The rates are sensitive to inhibition by hemicholinium-3 (HC-3), a competitive ChoK inhibitor, and to N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulphonamide (H-89), an agent commercialized as a specific cyclic-AMP-dependent protein kinase A (PKA) inhibitor. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). 1H HR-MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr-Purcell-Meiboom-Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). 31P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a 1H-decoupled pulse-acquire sequence ( TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and creatine (P = 0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P = 0.0001). Estimated concentrations of choline-containing metabolites increased from pre-invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To meet the metabolic demands of skeletal muscle, the vasculature supplying these vascular beds has to be connected to respond in a coordinated uniform manner, thus providing the necessary oxygen and nutrients during increased activity. The skeletal muscle microcirculation is the major resistance network controlling vascular blood supply and it is the integrity of the endothelium lining the blood vessels that is paramount in facilitating this action. Aging is a major risk factor for cardiovascular disease and is associated with significant increases in inflammatory agents that negatively impact the vasculature. Several inflammatory agents such as cytokines (tumor necrosis factor-a), advanced glycation products (AGEs), and matrix metalloproteinases (MMPs) along with storage cells for inflammatory mediators (mast cells) are associated with a chronic “low-grade inflammation” state that has been observed over the course of the aging process. Current research suggests that these age-related increases in inflammatory agents can disrupt the microvascular endothelium and thus impair blood flow. This impairment could exacerbate the common age-related disease states such as hypertension, diabetes, congestive heart failure, and sarcopenia, leading to increased mortality and morbidity. [ABSTRACT FROM AUTHOR]

Double resonance techniques such as INEPT (insensitive nuclei enhanced by polarization transfer) and JCP ( J cross-polarization) have previously been applied in vitro to enhance the SNR of low-sensitivity nuclei and detect altered metabolism, for example, with 13C magnetic resonance spectroscopy (MRS), where the 1H-13C scalar couplings are of the order of 130 Hz. The aim of the present study was to investigate the potential advantage of using JCP for the detection of phosphomonoesters (PME) and phosphodiesters (PDE) with 31P MRS in vivo. These metabolites are involved in membrane metabolism and their concentration is altered in tumors and other pathologies. JCP has been implemented and compared with INEPT and pulse-and-acquire in vivo both in unlocalized and in localized spectra in order to select the optimum method for in vivo applications for PME and PDE detection. The results suggest that JCP can give up to 20% more signal in the PME region and up to 70% more signal in the PDE region, with 20 to 70% lower power deposition than INEPT. Such enhancement could be used to reduce the measurement times for equivalent signal-to-noise ratios. The JCP sequence is, however, slightly more sensitive than INEPT to RF field inhomogeneities, as predicted from theory. Magn Reson Med, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

To measure hepatic concentrations of the fluorine-containing antimicrobial, sitafloxacin, usingin vivo19F magnetic resonance spectroscopy (MRS).Data were acquired from eight healthy subjects at 2, 5, 8 and 24 h following doses of 500 mg day−1 for 5 days using a1H/19F surface coil in a 1.5T clinical MR system. Tissue water was used as a reference.Estimated liver concentrations at 2 h were 15.0 ± 4.0 µg ml−1 (mean ± 95% CI), compared with 3.54 ± 0.58 µg ml−1 in plasma (n = 6), and fell below threshold concentrations (2 µg ml−1) by 24 h.19F MRS is able to detect and quantify sitafloxacin in the liver. There was no evidence for the hepatic retention of the drug. [ABSTRACT FROM AUTHOR]

Physical diminishes with ageing, but little is known of how the microvascular supply to skeletal muscle fibres is affected. To test the hypothesis that ageing alters blood flow control, we investigated network architecture and vasomotor responses of arterioles in the gluteus maximus muscle of young (2–3 months), adult (12–14 months) and old (18–20 months) C57BL6 male mice(Young, Adult and Old, respectively). Microvascular casts revealed that the total number, length and surface area of arteriolar segments (diameter, 10–50μm) were not significantly different across age-groups. However, for arterioles with diameter of 30μm, tortuosity and branch angles increased with age. In anaesthetized mice, second-order (2A) distributing arterioles had similar resting (17± 1μm) and maximal (37± 1μm) diameters and similar responsiveness to cumulative (10−10−10−4m) superfusion of acetylcholine or phenylephrine. With superfusate oxygen level raised from 0 to 21%, 2A arteriolar constriction in Young (11± 1μm) was greaterthan Adult and Old (5± 1μm). Observed 1 mm upstream from microiontophoresis of ACh (1μA, 1 s), conducted vasodilatation was 10± 1μm in Young, 17± 1μm in Adult and 6± 1μm in Old. With muscle contractions (2, 4 and 8 Hz; 30 s) arteriolar diameter increased similarly across age-groups (6± 1, 11± 1 and 18± 1μm, respectively). Muscle mass and active tension were similar across age-groups yet postcontraction vasodilatation recovered more rapidly in OldversusAdult and Young. With arteriolar network architecture maintained during ageing, the impairment in conducted vasodilatation and attenuation of postcontraction vasodilatation may compromise exercise tolerance. [ABSTRACT FROM AUTHOR]

Conducted vasodilation along arterioles manifests the spread of hyperpolarization through gap junction channels along endothelium. Whereas histamine increases the permeability of capillary and venular endothelium, its effect on the integrity of arteriolar endothelium is unknown. We tested whether histamine could inhibit conducted vasodilation. In second-order arterioles (2A) supplying the cremaster muscle of C57BL6, PECAM-1-/-, and eNOS-/- mice (8-12 wk), neither resting (16 ± 2 µm) nor maximal (38 ± 2 µm) diameters were different. Acetylcholine (ACh) microiontophoresis (1 µA, 500 ms pulse) triggered vasodilation that was conducted > 1400 µm along arterioles. Neither local (14 ± 2 µm) nor conducted vasodilation (10 ± 2 µm) was different among mice. Histamine (5 µM) had no effect on resting diameter or local vasodilation to ACh yet inhibited conduction by > 50% in C57BL6 and PECAM-1-/- mice (P < 0.05); this effect was abolished after blockade of NO synthase or of soluble guanylate cyclase. Washout of histamine restored conduction, though recovery was longer (P < 0.05) in PECAM-1-/- mice vs. C57BL6 mice. Remarkably, conducted vasodilation in eNOS-/- mice was insensitive to histamine. These findings indicate that histamine inhibits cell-to-cell coupling through an NO-dependent mechanism and suggests a dynamic interaction among intercellular adhesion molecules and gap junction channels along arteriolar endothelium. [ABSTRACT FROM AUTHOR]

Microvascular structure and function are key aspects of tissue and organ health. At approximately 40% of total body mass, skeletal muscle contains more microvessels than any other organ system in the body. Moreover, skeletal muscle is the most dynamic tissue in the body with the capacity to increase blood flow and metabolic rate 30- to 50- fold. Aging is associated with decrements in microvascular function and exercise tolerance that are poorly understood. Here, experts in their respective fields of microvascular structure and function are brought together to review the current state of knowledge regarding microvascular adaptations to aging. Reviews are drawn from human and animal studies and focus on age-related changes in sympathetic nervous system control of microvessels, capillary hemodynamics and oxygen pressure, microvascular network structure and functional integration, microvascular reactivity, whole muscle perfusion, and cellular contacts and inflammation. [ABSTRACT FROM AUTHOR]

Aims: To measure hepatic concentrations of the fluorine-containing antimicrobial, sitafloxacin, using in vivo(19)F magnetic resonance spectroscopy (MRS)., Methods: Data were acquired from eight healthy subjects at 2, 5, 8 and 24 h following doses of 500 mg day(-1) for 5 days using a (1)H/(19)F surface coil in a 1.5T clinical MR system. Tissue water was used as a reference., Results: Estimated liver concentrations at 2 h were 15.0 +/- 4.0 microg ml(-1) (mean +/- 95% CI), compared with 3.54 +/- 0.58 microg ml(-1) in plasma (n = 6), and fell below threshold concentrations (2 microg ml(-1)) by 24 h., Conclusions: (19)F MRS is able to detect and quantify sitafloxacin in the liver. There was no evidence for the hepatic retention of the drug.