Rapid multi‐echo measurement of brain metabolite T2 values at 7 T using a single‐shot spectroscopic Carr–Purcell–Meiboom–Gill sequence and prior information

We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times (T₂) from multiple spin‐echo data acquired with a single‐shot Carr–Purcell–Meiboom–Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time‐domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time‐domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and rapidly measure the T₂ values for the main singlet resonances in single‐volume MRS measurements in the brain. The proposed method can be generalized to any set of MRS experiments comprising repeated measurements of amplitude changes, e.g. as a function of an experimental parameter, such as TE, inversion time or diffusion weighting. Copyright © 2013 John Wiley & Sons, Ltd.     

The age dependence of T2 relaxation times of N‐acetyl aspartate,creatine and choline in the human brain at 3 and 4T

Knowledge of the T₂ age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T₂ values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T₂ values of N‐acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (T_E = 30–540 ms, 9 young and 11 elderly subjects) and 4T (T_E = 10–180 ms, 18 young and 14 elderly subjects) using single‐voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion‐recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different T_E range. Individual estimated T₂ values were statistically analyzed using the R programming language for the age dependence of T₂ values as well as the influence of the MM baseline handling. A significant decrease of T₂ values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T₂ values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T₂ values, we confirmed the age dependence of T₂ values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd.     

Case-Control Exploration of Relationships Between Early Rash or Liver Toxicity and Plasma Concentrations of Nevirapine and Primary Metabolites

Abstract

Objective: This investigation measured trough nevirapine and five oxidative metabolite concentrations in plasma specimens collected from patients who exhibited a rash or liver function abnormality during the first 6 weeks of treatment. Method: Patient selection came from three clinical trials, totaling 1,357 patients, from which frozen specimens had been stored and were available for assay. The control patients were matched according to trial, steroid use, CD4 cell count, gender, race, and hepatitis B/C status. Observed plasma metabolite concentrations were compared using signed rank tests. Results: A total of 49 case-control pairs were studied. Women had significantly greater exposure than men to nevirapine and four of the five metabolites at week 2, but the plasma concentrations were comparable by week 4. Steroid (prednisone) co-medication produced significantly different plasma nevirapine and metabolite concentrations for the majority of case-control comparisons at week 3, a week after cessation of steroid treatment, but only occasionally produced a measurable difference at other weeks. Conclusion: During the first 6 weeks of nevirapine therapy, the rashes and liver enzyme elevations that occurred appear to be idiosyncratic. There were no strong relationships observed between the plasma concentrations of nevirapine or any of its five metabolites to a casedefining event. The systemic exposure of the metabolite 12-hydroxynevirapine and its successor 4-carboxynevirapine, hypothesized in the skin rash female Brown Norway rat model as reactive intermediates for idiosyncratic immune-mediated adverse reactions, were comparable between case and control samples and were comparable in proportion to the precursor nevirapine exposure.     

In vitro human colonic fermentation of indigestible fraction isolated from lunch menus: impact on the gut metabolites and antioxidant capacity

The indigestible fraction (IF) isolated from three lunch menus: Modified Mexican Lunch (MM-L), Traditional Mexican Lunch (TM-L) and Alternative Mexican Lunch (AM-L), was studied in terms of antioxidant capacity (AOX) and metabolites produced through fermentation by human intestinal microbiota. IFs were isolated after withstanding in vitro gastrointestinal digestion and total soluble polyphenols (TSP), condensed tannins (CT), hydrolysable polyphenols (HP) and AOX (DPPH, FRAP) were evaluated. AOX, pH and bacterial metabolites profile changes were also monitored during in vitro colonic fermentation. Lunch menus showed differences in IF, TSP, CT and FRAP values (p<.05). TM-L had the highest TSP and CT contents (0.84 and 1.89?g/100?g DW, respectively). Changes in pH and AOX during fermentation were time-dependent and substrate-dependent (p<.05). Butyric acid production was not significantly modified by the IFs (p>.05). Fifty-seven microbiota-produced volatile compounds were detected by SPME-GC–MS. This study shows the potential effects of food habits on bacterial metabolite production.     

Plasma Colloid Osmotic Pressure During Open-Heart Surgery Using Non-Colloid or Colloid Priming Solution in the Extracorporeal Circuit

Two different priming solutions for the heart-lung machine were compared in 14 patients during aortic valve replacement. Colloid osmotic pressure (COP), and albumin in plasma, blood erythrocyte volume fraction (B-EVF) and arterial oxygen tension (PaO₂) (FIO₂ = 1.0) were followed before, during and after perfusion. The two priming solutions were 2000 ml Ringerdex^® (7 patients) or 1800 ml Ringerdex + 200 ml 20% albumin^® (7 patients). COP and B-EVF were normal before bypass. After 10 min on bypass, when about 1 000 ml of crystalloid cardioplegic solution had been given, COP was reduced by about 50% and B-EVF fell to 23%, indicating a small loss of water from the circulation when compared with in vitro dilution curves. COP was slightly lower in the non-colloid group (p < 0.02). Both COP and B-EVF remained unchanged during perfusion, despite transfusica from the heart-lung machine of a mixture of blood and crystalloid solution with a calculated very low COP (6 mmHg) and B-EVF (15 %). After perfusion the restitution of COP and B-EVF was rapid and parallel. Both returned to normal levels after 2 hours. There was a good correlation between COP and albumin measured in the same plasma samples (r = 0.83, p < 0.001). At one hour after bypass PaO₂ (FIO₂ = 1.0) tended to decrease in the non-colloid group, compared with the preperfusion level. 40 g of albumin was a too small amount of colloid to diminish substantially the reduction of COP during perfusion. The unchanged levels of COP and B-EVF during perfusion, despite further dilution as well as the parallel normalization after perfusion, can only be explained by loss of water from the circulation.     

Electrochemistry of calcium precipitating bacteria in orthodontic wire

BackgroundCalculus composed of inorganic and organic components with bacteria formed on teeth gets deposited on orthodontic wires. The reason for calculus formation and impact of calcium precipitating bacteria (CPB) on orthodontic wire were studied. A pilot study on electrochemical characterization of CPB on orthodontic wires was done.MethodsCPB were isolated from orthodontic patients and identified by molecular techniques. The electrochemical behavior of two isolates (CPB-1 and CPB-3) on orthodontic wires was studied by employing polarization and impedance techniques. The CPB morphology by scanning electron microscopy and chemical characterization of CPB and tooth pulp stone were studied by Fourier transform infrared (FTIR) and X-ray diffraction (XRD).ResultsThe two isolates Bacillus megaterium (CPB-1) and Paenibacillus sp. (CPB-3) identified with 16S rRNA sequencing method increased pH of B4 medium from 5.32 to 8.3. The carboxylic acid and phosphate groups identified in FTIR analysis acted as nucleation sites for calcium deposition. The biogenic crystal phases identified in teeth pulp stone by XRD were similar to bacterial isolates cultured in the laboratory. The electrochemical studies with two CPB species revealed that biogenic calcium phosphate species act as cathodic inhibitors on orthodontic wire.ConclusionThe present study concluded that teeth pulp stone formation is due to CPB and high pH determines the mineralization process. Diffusion process and dispersive capacitive behavior indicate that the chloride ions may penetrate through calcium deposits and initiate pitting corrosion on orthodontic wire which may enhance the leaching of toxic elements in saliva.     

Comparative analysis of different methods used for molecular characterization of Burkholderia cepacia complex isolated from noncystic fibrosis conditions

PurposeBurkholderia is a Gram-negative opportunistic bacterium capable of causing severe nosocomial infections. The aim of this study was to characterize Burkholderia cepacia complex and to compare different molecular methods used in its characterization.MethodsIn this study, 45 isolates of Burkholderia cepacia complex (Bcc) isolated from clinical cases were subjected to RAPD (Random amplified polymorphic DNA), recA-RFLP (Restriction fragment length polymorphism), 16SrDNA-RFLP, whole-cell protein analysis, recA DNA sequencing and biofilm assay.ResultsOf the 45 isolates tested, 97.7% were sensitive to ceftazidime, 82.2% were sensitive to Cotrimoxazole, 73.3% were sensitive to meropenem, 55.5% were sensitive to minocycline and 42.2% were sensitive to levofloxacin. Majority of the isolates harbored all the tested virulence genes except bpeA and cblA. The RAPD generated 11 groups (R1-R11), recA-RFLP 10 groups (A1-A10), 16SrRNA-RFLP 5 groups (S1–S5) and SDS-PAGE (Sodium Dodecyl Sulphate-Polyacrylamide gel electrophoresis) whole cell protein analysis revealed 12 groups (C1–C12). recA sequencing revealed that most of the isolates belonging to the genomovar III Burkholderia cenocepacia. Though all the methods are found to be efficient in differentiating Burkholderia spp., recA-RFLP was highly discriminatory at 96% similarity value. The study also identified a new strain Burkholderia pseudomultivorans for the first time in the country. Further, recA sequencing could identify the strains to species level. Majority of the multidrug-resistant strains also showed moderate to strong biofilm-forming ability, which further contributes to the virulence characteristics of the pathogens.ConclusionsThe study highlights the importance of combination of molecular methods to characterize Burkholderia cepacia complex. Molecular typing of these human pathogens yields important information for the clinicians in order to initiate the most appropriate therapy in the case of severe infections and to implement preventive measures for the effective control of transmission of Burkholderia spp.