Choline-Containing Compounds in Human Astrocytomas Studied by 1H NMR Spectroscopy In Vivo and In Vitro

Abstract: We have studied 14 patients with different grades of astrocytomas using ¹H NMR spectroscopy in vivo. Typically, astrocytomas exhibited a low N -acetyl-aspartate peak, a prominent signal from choline group-containing compounds, and lactate in the ¹H NMR spectra in vivo. The uncorrected choline/creatine + phosphocreatine peak area ratios were higher in tumors than in normal brain tissue. Absolute concentration of choline-containing compounds (1.74 ± 0.09 mmol/L) in the normal brain tissue was not different in any grade of astrocytoma, but total creatine concentration in healthy brain (7.49 ± 0.30 mmol/L) was higher than that in grade IV astrocytomas (4.84 ± 0.89 mmol/L). Relaxation constants of choline-containing compounds did not differ in tumors from those determined in normal brain. Perchloric acid extracts of biopsy samples from 35 astrocytomas and 13 samples of normal temporal white matter were analyzed with ¹H NMR. Total concentration of choline-containing compounds did not differ between controls and any grade of astrocytoma when the quantification was done in vitro. It is interesting that phosphorylcholine concentration was about twofold greater in grade IV astrocytomas than in controls or other grades of astrocytomas. We conclude that high phosphorylcholine in grade IV astrocytomas may be an indicator of degree of malignancy. The proportional changes within the group of choline-containing compounds observed in vitro were not reflected in the NMR properties of choline signal in vivo.     

Alternative operation models for using a feed‐in terminal as a part of the forest chip supply system for a CHP plant

The fuel supply of forest chips has to adapt to the annual fluctuations of power and heat generation. This creates inefficiency and unbalances the capacity utilization of the fuel supply fleet in the direct fuel supplies from roadside storages to power and heat generation. Terminals can offer an alternative approach for the fleet management of fuel supplies in terms of smoothing the unbalanced fleet use towards more even year‐round operations. The aim of the study was to compare the supply costs of a conventional direct forest chip supply to an alternative fuel supply with the use of a feed‐in terminal using the discrete‐event simulation method. The influences of the terminal location, terminal investment cost, outbound terminal transport method, terminal truck utilization and quality changes of terminal‐stored forest chips for the fuel supply cost were studied in the case environment. By introducing a feed‐in terminal and a shuttle truck for the transports of terminal‐stored forest chips, the total supply cost was 1.4% higher than the direct fuel supply scenario. In terminal scenarios, the supply costs increased 1–2% if the cost of the terminal investment increased 30%, the distance to the terminal increased from 5 to 30 km or the total annual use of a terminal truck decreased 1500 h. Moreover, a 1 per cent point per month increase in the dry matter loss of terminal‐stored chips increased the total supply cost 1%. The study revealed that with the relatively low additional cost, the feed‐in terminal can be introduced to the conventional forest chip supply. Cost compensation can be gained through the higher annual use of a fuel supply fleet and more secured fuel supply to power plants by decreasing the need for supplement fuel, which can be more expensive at a time of the highest fuel demand.     

Comparison of sensitivity between gas chromatography–low-resolution mass spectrometry and gas chromatography–high-resolution mass spectrometry for determining metandienone metabolites in urine

In doping control laboratories the misuse of anabolic androgenic steroids is commonly investigated in urine by gas chromatography–low-resolution mass spectrometry with selected ion monitoring (GC–LRMS–SIM). By using high-resolution mass spectrometry (HRMS) detection sensitivity is improved due to reduction of biological background. In our study HRMS and LRMS methods were compared to each other. Two different sets were measured both with HRMS and LRMS. In the first set metandienone (I) metabolites 17α-methyl-5β-androstan-3α,17β-diol (II), 17-epimetandienone (III), 17β-methyl-5β-androst-1-ene-3α,17α-diol (IV) and 6β-hydroxymetandienone (V) were spiked in urine extract prepared by solid-phase extraction, hydrolysis with β-glucuronidase from Escherichia coli and liquid–liquid extraction. In the second set the metabolites were first spiked in blank urine samples of four male persons before pretreatment. Concentration range of the spiked metabolites was 0.1–10 ng/ml in both sets. With HRMS (resolution of 5000) detection limits were 2–10 times lower than with LRMS. However, also with the HRMS method the biological background hampered detection and compounds from matrix were coeluted with some metabolites. For this reason the S/N values of the metabolites spiked had to be first compared to S/N values of coeluted matrix compounds to get any idea of detection limits. At trace concentrations selective isolation procedures should be implemented in order to confirm a positive result. The results suggest that metandienone misuse can be detected by HRMS for a prolonged period after stopping the intake of metandienone.     

Responses of Strawberry (Fragaria × ananassa) to Supplemental UV-B Radiation and Selenium Under Field Conditions

In greenhouse experiments, selenium (Se) has been shown to defend plants against detrimental effects of heavy UV-B radiation stress. The aim of this study was to investigate whether this positive effect can be found in open-field conditions with enhancement of UV-B radiation. In the experiment, conducted with strawberry (Fragaria×ananassa, cultivars “Jonsok” and “Polka”) over two growing seasons, plants were exposed to UV-B radiation (including UV-A) and cultivated without Se or supplied with Se added at two levels (0.1 and 1.0 mg kg⁻¹). The plants were monitored for growth, flavonoids, chlorophyll fluorescence, net photosynthesis as well as tissue and cell structure. Photosystem II was observed to be sensitive to UV-B stress under field conditions. In the leaves, a decrease in F_v/F_m was seen at the end of the growing season, implying a cumulative effect of UV-B stress. Several parameters, especially cell and tissue structures, were affected by UV-B and UV-A treatments, which proves the need for UV-A control in outdoor UV-B supplementation studies. Addition of Se did not ameliorate the harmful effects of UV-B but the lower Se-increment level increased leaf growth. The effects of UV-B and Se differed during the two experimental years, indicating the need to repeat experiments during several growing seasons.     

The accuracy of several multiple sequence alignment programs for proteins

Background  

There have been many algorithms and software programs implemented for the inference of multiple sequence alignments of protein and DNA sequences. The "true" alignment is usually unknown due to the incomplete knowledge of the evolutionary history of the sequences, making it difficult to gauge the relative accuracy of the programs.     

Endotoxemia is associated with an adverse metabolic profile

Our aim was to analyze whether endotoxemia, i.e. translocation of LPS to circulation, is reflected in the serum metabolic profile in a general population and in participants with cardiometabolic disorders. We investigated three Finnish cohorts separately and in a meta-analysis (n = 7178), namely population-based FINRISK97, FinnTwin16 consisting of young adult twins, and Parogene, a random cohort of cardiac patients. Endotoxemia was determined as serum LPS activity and metabolome by an NMR platform. Potential effects of body mass index (BMI), smoking, metabolic syndrome (MetS), and coronary heart disease (CHD) status were considered. Endotoxemia was directly associated with concentrations of VLDL, IDL, LDL, and small HDL lipoproteins, VLDL particle diameter, total fatty acids (FA), glycoprotein acetyls (GlycA), aromatic and branched-chain amino acids, and Glc, and inversely associated with concentration of large HDL, diameters of LDL and HDL, as well as unsaturation degree of FAs. Some of these disadvantageous associations were significantly stronger in smokers and subjects with high BMI, but did not differ between participants with different CHD status. In participants with MetS, however, the associations of endotoxemia with FA parameters and GlycA were particularly strong. The metabolic profile in endotoxemia appears highly adverse, involving several inflammatory characters and risk factors for cardiometabolic disorders.     

Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.     

Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease

Summary Salla disease is an inherited lysosomal storage disorder caused by accumulation of free sialic acid in the lysosomes. Lamp genes, lamp A and lamp B (lysosome associated membrane proteins), are the first known genes encoding for human lysosomal membrane proteins. Absence of linkage in a large group of families shows that lamp genes are not involved in Salla disease. The lamp genes were localized, using Southern hybridization in hamster — human hybrid cell panels, to chromosomes 13 (lamp A) and X (lamp B).