Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex

The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (¹H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla ¹H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement of clinical symptoms. Sarcosine, two grams administered daily, seems to be an effective adjuvant in the pharmacotherapy of schizophrenia.     

A Combined Metabolomic and Proteomic Analysis of Gestational Diabetes Mellitus

The aim of this pilot study was to apply a novel combined metabolomic and proteomic approach in analysis of gestational diabetes mellitus. The investigation was performed with plasma samples derived from pregnant women with diagnosed gestational diabetes mellitus (n = 18) and a matched control group (n = 13). The mass spectrometry-based analyses allowed to determine 42 free amino acids and low molecular-weight peptide profiles. Different expressions of several peptides and altered amino acid profiles were observed in the analyzed groups. The combination of proteomic and metabolomic data allowed obtaining the model with a high discriminatory power, where amino acids ethanolamine, l-citrulline, l-asparagine, and peptide ions with m/z 1488.59; 4111.89 and 2913.15 had the highest contribution to the model. The sensitivity (94.44%) and specificity (84.62%), as well as the total group membership classification value (90.32%) calculated from the post hoc classification matrix of a joint model were the highest when compared with a single analysis of either amino acid levels or peptide ion intensities. The obtained results indicated a high potential of integration of proteomic and metabolomics analysis regardless the sample size. This promising approach together with clinical evaluation of the subjects can also be used in the study of other diseases.     

Sphingolipid metabolism in colorectal adenomas varies depending on histological architecture of polyps and grade of nuclear dysplasia

Incidence of colorectal cancer (CRC) is growing worldwide. Pathogenetic mechanisms responsible for its onset and progression need further clarification. Colorectal adenomatous polyps are precancerous lesions with malignant potential dependent on histological architecture and grade of nuclear dysplasia. One of the factors conditioning CRC development are abnormalities in sphingolipid metabolism. The aim of this study was to assess the levels of sphingolipids in human colorectal adenomas. The control group (C, n = 12) consisted of patients with no colonic polyps. The examined group consisted of patients with prior diagnosed colonic polyps, qualified to endoscopic polypectomy. This group was further divided due to histological architecture into tubular adenomas group (TA, n = 10), tubulovillous adenomas with low‐grade dysplasia (LGD‐TVA, n = 10), and tubulovillous adenomas group with high‐grade dysplasia (HGD‐TVA, n = 11). In tissue samples, sphingolipd metabolite contents were measured using high performance liquid chromatography (HPLC). In cases of polypoid lesions with low malignancy potential (tubular adenomas), concentration of ceramide, which is characterized by proapoptotic and anti‐proliferative properties, increases compared with control group (p < 0.05), whereas content of sphingosine‐1‐phosphate with anti‐apoptotic and stimulating cellular proliferation properties is reduced in comparison with control group (p < 0.05). On the contrary, in cases of more advanced form of adenomatous polyps (tubulovillous adenomas with high‐grade dysplasia), the ceramide level decreases compared with control group (p < 0.05) while sphingosine‐1‐phosphate concentration is elevated (p < 0.05). We found that concentrations of pro‐apoptotic ceramide are decreased and pro‐proliferative S1P levels are increased in polypoid lesions with high malignancy potential, and it was the opposite in those with low malignancy potential.     

Materials Displaying Neural Growth Factor Gradients and Applications in Neural Differentiation of Embryoid Body Cells

The critical growth factor density required to support neural lineage generation from mouse embryonic stem cells is assessed by constructing a surface density gradient of immobilized nerve growth factor (NGF) from a plasma polymer film base. A chemical surface gradient varying from high hydroxyl group density to high aldehyde group density is prepared through diffusion‐controlled plasma polymerization of two monomers (ethanol and propionaldehyde) under a moving mask. NGF density gradients are then produced by reductive amination with the aldehyde groups on the plasma polymer surface. Mouse embryoid body derived (mEB) cell differentiation on the gradient surface is evaluated by immunofluorescence staining against Nestin. mEB cell density and the percentage of Nestin‐positive cells increase with increasing NGF density up to a critical value corresponding to 52.9 ng cm^?2, above which cell attachment and differentiation do not increase further. This gradient‐based screening approach allows the growth factor surface densities to be optimized for biomaterials intended for cell differentiation or expansion, which is highly relevant to creating efficient manufacture processes for cell therapies.     

The effects of Aphis fabae infestation on the antioxidant response and heavy metal content in field grown Philadelphus coronarius plants

The purpose of this study was to explore a possible relationship between the soil availability of metals and their concentrations in various parts of Philadelphuscoronarius plants. Moreover, the possible impact of an aphid infestation on the contamination and antioxidant response of plants from the urban environment of Kraków and the reference rural area of Zagaje Stradowskie (southern Poland) was analyzed. The contents of the glutathione, proline, non-protein − SH groups, antioxidants, and phosphorous and the levels of guaiacol peroxidase and catalase activity in leaves and shoots either infested or not by the aphid Aphis fabae Scop., were measured. The potential bioavailability of metals (Cd; Cu; Ni; Pb; Zn) in the soil and their concentrations in P. coronarius plants originating from both sites were compared.The antioxidant responses were generally elevated in the plants in the polluted area. Such reactions were additionally changed by aphid infestation. Generally, the concentrations of metals in the HNO₃ and CaCl₂ extractants of the soils from two layers at the 0-20 and 20-40 cm depths from the polluted area were higher than in those from the reference area. Such differences were found for nickel and lead (in all examined extractants), zinc (in soil extractants from the layer at 20-40 cm) and cadmium (in HNO₃ extractants). Significant positive relationships between the lead concentrations in the soil and in the plants were found. In the parts of plants from the polluted area, higher concentrations of Pb and Zn (leaves and shoots) and Cd (shoots) were recorded. The shoots and leaves of plants infested with aphids had higher concentrations of Zn but lower Pb. Moreover, their leaves had higher contaminations of Cu and Ni. In conclusion, aphids affected not only the antioxidant response of the plants but also their contamination with metals, especially contamination of the leaves.     

Biodegradation of plastified starch obtained by corotation twin‐screw extrusion

The potato starch has been subjected to plastification with glycerol using twin‐screw extruder in different conditions. The structure of obtained samples has been determined by Fourier transform infrared spectroscopy with attenuated total reflectance methods. The average molecular weights by chromatographic method and solubility in water have also been determined. Next, the susceptibility of all samples to activity of microorganisms such as bacteria, fungi, and actinomycetes has been checked. It has been stated that increasing rotation speed of extruder screws causes the degradation of starch slightly, influencing the later bio‐decomposition. The actinomycetes are the most effective in this process. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers     

Subsampling inference for the autocovariances and autocorrelations of long‐memory heavy‐ tailed linear time series

We provide a self‐normalization for the sample autocovariances and autocorrelations of a linear, long‐memory time series with innovations that have either finite fourth moment or are heavy‐tailed with tail index 2 < α < 4. In the asymptotic distribution of the sample autocovariance there are three rates of convergence that depend on the interplay between the memory parameter d and α, and which consequently lead to three different limit distributions; for the sample autocorrelation the limit distribution only depends on d. We introduce a self‐normalized sample autocovariance statistic, which is computable without knowledge of α or d (or their relationship), and which converges to a non‐degenerate distribution. We also treat self‐normalization of the autocorrelations. The sampling distributions can then be approximated non‐parametrically by subsampling, as the corresponding asymptotic distribution is still parameter‐dependent. The subsampling‐based confidence intervals for the process autocovariances and autocorrelations are shown to have satisfactory empirical coverage rates in a simulation study. The impact of subsampling block size on the coverage is assessed. The methodology is further applied to the log‐squared returns of Merck stock.     

The influence of calcination parameters on free calcium oxide content in natural hydroxyapatite

Effect of calcining temperature and time on the content of free CaO in hydroxyapatite of natural origin is presented. Hydroxyapatite was obtained from pork bones in the course of a three-stage process: hydrolysis with the application of lactic acid, pre-calcination at 600 °C and main calcination stage within the temperature range of 750-950 °C. Calcination was conducted in an electrically heated stationary chamber oven in air atmosphere and in a laboratory scale rotary kiln equipped with a gas burner. The FT-IR spectra confirmed that all organic substances were removed during the calcination process. An increase in free calcium oxide content in hydroxyapatite from 0.003% to 0.023% was caused by the increase of calcining temperature from 750 °C to 950 °C respectively. Calcining time at 950 °C gave a distinct impact upon free CaO content ranging from 0.014% (2 h) to 0.023% (3 h). Hydroxyapatite calcined in the rotary kiln contained the lowest amount of free calcium oxide: 0.002% (750 °C) and 0.003% (950 °C). A method of neutralizing of free calcium oxide, present in calcined hydroxyapatite powders of natural origin, through CaO transformation into hydroxyapatite by application of diluted thermic phosphoric acid has been developed.     

Nanostructured systems based on SBS epoxidized triblock copolymers and well-dispersed alumina/epoxy matrix composites

In the present research, the effect of addition of (1 wt.% and 3 wt.%) alumina nanoparticles (Al₂O₃) to epoxy modified by poly(styrene-b-butadiene-b-styrene) (SBS) epoxidized triblock copolymer was studied. The microstructure of final hybrid composites was studied with atomic force microscopy (AFM). Composites showed homogeneously dispersed Al₂O₃ nanoparticles in the epoxy matrix containing polystyrene (PS) microphase separated nanodomains. Dynamic mechanical analyses (DMA), flexural and fracture toughness investigations were carried out. The glass transition temperature of epoxy matrix has been retained unchanged by the addition of Al₂O₃ nanoparticles. The nanostructured epoxy systems based on SBS epoxidized triblock copolymer and well-dispersed Al₂O₃ nanoparticles allowed an increase in fracture toughness maintaining the transparency and stiffness of neat epoxy.