Increased Beta-Hydroxybutyrate Level Is Not Sufficient for the Neuroprotective Effect of Long-Term Ketogenic Diet in an Animal Model of Early Parkinson’s Disease. Exploration of Brain and Liver Energy Metabolism Markers

The benefits of a ketogenic diet in childhood epilepsy steered up hope for neuroprotective effects of hyperketonemia in Parkinson’s disease (PD). There are multiple theoretical reasons but very little actual experimental proof or clinical trials. We examined the long-term effects of the ketogenic diet in an animal model of early PD. A progressive, selective dopaminergic medium size lesion was induced by 6-OHDA injection into the medial forebrain bundle. Animals were kept on the stringent ketogenic diet (1% carbohydrates, 8% protein, 70% fat) for 3 weeks prior and 4 weeks after the brain operation. Locomotor activity, neuron count, dopaminergic terminal density, dopamine level, and turnover were analyzed at three time-points post-lesion, up to 4 weeks after the operation. Energy metabolism parameters (glycogen, mitochondrial complex I and IV, lactate, beta-hydroxybutyrate, glucose) were analyzed in the brain and liver or plasma. Protein expression of enzymes essential for gluconeogenesis (PEPCK, G6PC) and glucose utilization (GCK) was analyzed in the liver. Despite long-term hyperketonemia pre- and post-lesion, the ketogenic diet did not protect against 6-OHDA-induced dopaminergic neuron lesions. The ketogenic diet only tended to improve locomotor activity and normalize DA turnover in the striatum. Rats fed 7 weeks in total with a restrictive ketogenic diet maintained normoglycemia, and neither gluconeogenesis nor glycogenolysis in the liver was responsible for this effect. Therefore, potentially, the ketogenic diet could be therapeutically helpful to support the late compensatory mechanisms active via glial cells but does not necessarily act against the oxidative stress-induced parkinsonian neurodegeneration itself. A word of caution is required as the stringent ketogenic diet itself also carries the risk of unwanted side effects, so it is important to study the long-term effects of such treatments. More detailed metabolic long-term studies using unified diet parameters are required, and human vs. animal differences should be taken under consideration.     

Synthesis and Structure of Novel Copper(II) Complexes with N,O- or N,N-Donors as Radical Scavengers and a Functional Model of the Active Sites in Metalloenzymes

To evaluate the antioxidant activity of potential synthetic enzyme mimetics, we prepared new five copper(II) complexes via a self-assembly method and named them [Cu(2-(HOCH₂)py)₃](ClO₄)₂ (1), [Cu(2-(HOCH₂)py)₂(H₂O)₂]SiF₆ (2), [Cu₂(2-(HOCH₂CH₂)py)₂(2-(OCH₂CH₂)py)₂](ClO₄)₂ (3), [Cu(pyBIm)₃](BF₄)₂·1.5H₂O (4) and [Cu(py₂C(OH)₂)₂](ClO₄)₂ (5). The synthetic protocol involved N,O- or N,N-donors: 2-(hydroxymethyl)pyridine (2-(HOCH₂)py), 2-(hydroxyethyl)pyridine (2-(HOCH₂CH₂)py), 2-(2-pyridyl)benzimidazole (pyBIm), di(2-pyridyl)ketone (py₂CO). The obtained Cu(II) complexes were fully characterised by elemental analysis, FTIR, EPR, UV-Vis, single-crystal X-ray diffraction and Hirshfeld surface analysis. Crystallographic and spectroscopic analyses confirmed chromophores of both monomeric ({CuN₃O₃} (1), {CuN₂O₄} (2), {CuN₆} (4), {CuN₄O₂} (5)) and dimeric complex ({CuN₂O₃} (3)). Most of the obtained species possessed a distorted octahedral environment, except dimer 3, which consisted of two copper centres with square pyramidal geometries. The water-soluble compounds (1, 3 and 5) were selected for biological testing. The results of the study revealed that complex 1 in solutions displayed better radical scavenging activity than complexes 3, 5 and free ligands. Therefore, complex 1 has been selected for further studies to test its activity as an enzyme mimetic. The chosen compound was tested on the erythrocyte lysate of two groups of patients after undergoing chemotherapy and chemoradiotherapy. The effect of the tested compound (1) on enzyme activity levels (TAS, SOD and CAT) suggests that the selected complex can be treated as a functional mimetic of the enzymes.     

Crystallographic orientation inhomogeneity and crystal splitting in biogenic calcite

The calcitic prismatic units forming the outer shell of the bivalve Pinctada margaritifera have been analysed using scanning electron microscopy–electron back-scatter diffraction, transmission electron microscopy and atomic force microscopy. In the initial stages of growth, the individual prismatic units are single crystals. Their crystalline orientation is not consistent but rather changes gradually during growth. The gradients in crystallographic orientation occur mainly in a direction parallel to the long axis of the prism, i.e. perpendicular to the shell surface and do not show preferential tilting along any of the calcite lattice axes. At a certain growth stage, gradients begin to spread and diverge, implying that the prismatic units split into several crystalline domains. In this way, a branched crystal, in which the ends of the branches are independent crystalline domains, is formed. At the nanometre scale, the material is composed of slightly misoriented domains, which are separated by planes approximately perpendicular to the c-axis. Orientational gradients and splitting processes are described in biocrystals for the first time and are undoubtedly related to the high content of intracrystalline organic molecules, although the way in which these act to induce the observed crystalline patterns is a matter of future research.     

Identification of diffusive transport properties of poly(vinyl alcohol) hydrogels from reservoir test

In this paper the identification of diffusion coefficient, retardation factor and surface distribution coefficient for selected salts in poly(vinyl alcohol) hydrogels is performed. The identification of the transport parameters is based on the previously developed inverse problem technique using experimental data from the reservoir test and the solution of the diffusive transport equation with linear equilibrium sorption. The estimated values of diffusion coefficient are: for physiological fluid (6.30 ± 0.10) × 10^? 10 m²/s, for 1 M NaCl (6.42 ± 0.39) × 10^? 10 m²/s, and for 1 M KCl (7.94 ± 0.38) × 10^? 10 m²/s. The retardation factor for all tested materials and salts is equal or close to one. The average value of the effective surface distribution coefficient is equal to 0.5.     

Dual nonlinear correlator based on computer controlled joint transform processor: Digital analysis and optical results

Abstract

The hybrid optoelectronic processor, presented in this paper, realizes the dual nonlinear correlation (DNC) in a set-up based on a two-step nonlinear joint transform correlator architecture. In the first step three power spectrum distributions (input scene power spectrum, reference target power spectrum, and the joint power spectrum) necessary for the nonlinear processing are captured with a CCD camera. Nonlinear modification of the joint power spectrum, which does not have to be symmetrical in the input and reference channels, is introduced digitally. In the second step, the modified joint power spectrum is Fourier transformed optically. Numerical analysis of this processor shows a crucial influence of the dynamic range and the limited number of grey levels of the CCD camera during image acquisition in the first step, on the output signal parameters and the discrimination capability of the set-up. Optical results of recognition obtained for noise-free segmented input scenes show that the set-up enables the realization of various correlation operations as CMF, POF, IF, PPC, etc. without any filters and that the discrimination capability is easy to control by a proper selection of the type of nonlinear processing.     

Selective derivatization of cytosine and methylcytosine moieties with 2-bromoacetophenone for submicrogram DNA methylation analysis by reversed phase HPLC with spectrofluorimetric detection

In eukaryotes, actual DNA methylation patterns provide biologically important information, for which both, genome-wide and locus-specific methylation at cytosine residues have been extensively studied. The original contribution of this work relies on the selective derivatization of cytosine moieties with 2-bromoacetophenone for the determination of global DNA methylation by reversed phase high performance liquid chromatography with spectrofluorimetric detection. The important features of the proposed procedure are as follows: (1) no need for the elimination of RNA, (2) detection limits for cytidine, 2'-deoxycytidine, 5-methylcytidine, and 5-methyl-2'-deoxycytidine in the range of 14.4-22.7 fmol, (3) feasibility for the detection of 0.06% of methylation in a low amount of DNA (80 ng), (4) potential viability for the evaluation of RNA methylation, and (5) relative simplicity in terms of analytical instrumentation and personnel training. The results obtained in the analysis of salmon testes DNA and nucleic acids from plant, human blood, and earthworms demonstrate the utility of the proposed procedure in biological studies and, in particular, for evaluation of the potential effect of environmental factors on actual DNA methylation in different types of living organisms.     

Sol–gel-processed silica/polydimethylsiloxane/calcium xerogels as polymeric matrices for Metronidazole delivery system

Silica, silica/polydimethylsiloxane and silica/polydimethylsiloxane/calcium xerogels were examined as polymeric carriers for the controlled release of drug—Metronidazole. Characterization assays comprised analysis of the matrix by Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET) and scanning electron microscope (SEM) techniques and further monitoring in the ultraviolet and visible light regions (UV–Vis) of the in vitro release of the drug over time. Using tetramethoxysilane (TMOS) as a precursor of silica matrix and polydimethylsiloxane (PDMS) and calcium ions as additives, xerogels with different morphology and physical properties were obtained. The applied modifications diminished the porosity and hydrophilicity of the silica matrix as well as reduced the release of drug. Based on the presented results of this study, it may be stated that applied xerogel matrices, pure silica (SiO₂) and modified silica (SiO₂–CaO, SiO₂–PDMS and SiO₂–CaO–PDMS), could be promising candidates for the formulation in local delivery systems.     

Corticosterone Administration Alters White Matter Tract Structure and Reduces Gliosis in the Sub-Acute Phase of Experimental Stroke

White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been suggested to be an independent predictor of post-stroke recovery. However, the factors that influence WMT remodeling are poorly understood. Cortisol is a steroid hormone released in response to prolonged stress, and elevated levels of cortisol have been reported to interfere with brain recovery. The objective of this study was to investigate the influence of corticosterone (CORT; the rodent equivalent of cortisol) on WMT structure post-stroke. Photothrombotic stroke (or sham surgery) was induced in 8-week-old male C57BL/6 mice. At 72 h, mice were exposed to standard drinking water ± CORT (100 µg/mL). After two weeks of CORT administration, mice were euthanised and brain tissue collected for histological and biochemical analysis of WMT (particularly the corpus callosum and corticospinal tract). CORT administration was associated with increased tissue loss within the ipsilateral hemisphere, and modest and inconsistent WMT reorganization. Further, a structural and molecular analysis of the WMT components suggested that CORT exerted effects over axons and glial cells. Our findings highlight that CORT at stress-like levels can moderately influence the reorganization and microstructure of WMT post-stroke.     

The perfluoroalkyl substances (PFASs) contamination of fruits and vegetables

Fruit and vegetables play a major role in human nutrition due to richness of nutrients, dietary fibre, and phytochemicals. As dietary intake is identified as one of the dominant exposure pathways to perfluoroalkyl substances (PFASs), a cross-sectional study involving determination of their levels in food of plant origin has been conducted. Locally-grown and imported fruit and vegetable samples, collected in 2016 were inspected for 10 perfluoroalkyl acids (PFAAs) using QuEChERS as sample pre-treatment procedure followed by micro-HPLC-MS/MS. Three of 10 target analytes, perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) were quantitatively determined. The detection frequency for PFASs across the 55 samples analysed was less than 10%. The major contributor of the total PFASs concentration in the investigated group was PFBA for which the concentration, reported only for banana, apple and orange samples, was 50.740 ng g^?1 ww. The most often detected compound was PFOA. The origin and growing region are possible factors with the potential to influence PFASs distribution profile and their levels in food.     

Effect of food processing of pearl millet (Pennisetum glaucum) IKMP‐5 on the level of phenolics,phytate, iron and zinc

Pearl millet is consumed as a staple food in semi‐arid tropical regions. With a view to upgrading the micronutrient status of pearl millet‐based foods, the effects of single operations and of porridge preparation scenarios on levels and in vitro solubility (IVS) of iron and zinc and mineral complexing factors (phytates: inositol phosphates and phenolic compounds) were tested. Disc milling of grain may add significant iron but this is not necessarily IVS iron. Soaking of grains results in a 25% loss of iron, but also facilitates endogenous phytate degradation, particularly when combined with milling and cooking. Germination and lactic acid fermentation both result in partial phytate degradation. Cooking does not decompose phytates, but results in complex formation of phenolic compounds as measured by a significant reduction in reactive hydroxyl groups. Because of its different distribution in the grain, zinc is generally less affected than iron. Phytate reduction by endogenous phytases is inhibited at low pH as caused by fermentation. Kanwa (alkaline rock salt) could be a functional cooking ingredient as a source of minerals and to react with phenolic substances. The relative IVS of iron was doubled by germination of grain and increased 3‐fold by fermentation of wholemeal slurry. Zinc IVS tended to increase on cooking with kanwa, but decreased in cooked fermented flour. Copyright © 2006 Society of Chemical Industry