Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats

Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (n = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-Lep), and maintained on standard rat chow for 18 weeks. A second group (n = 15) was calorically-restricted to match the weight of the rAAV-Lep group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue Ucp-1 mRNA expression than rAAV-Lep rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition.     

Molecular Mechanism of the Anti-Inflammatory Action of Heparin

Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.     

Encapsulation of Synthesized Plant Growth Regulator Based on Copper(II) Complex in Chitosan/Alginate Microcapsules

A new copper complex, trans-diaqua-trans-bis [1-hydroxy-1,2-di (methoxycarbonyl) ethenato] copper (abbreviation Cu(II) complex), was synthesized and its plant growth regulation properties were investigated. The results show a sharp dependence of growth regulation activity of the Cu(II) complex on the type of culture and its concentration. New plant growth regulator accelerated the development of the corn root system (the increase in both length and weight) but showed a smaller effect on the development of the wheat and barley root systems. Stimulation of corn growth decreased with increasing Cu(II) complex concentration from 0.0001% to 0.01% (inhibition at high concentrations—0.01%). The development of corn stems was also accelerated but to a lesser extent. Chitosan-coated calcium alginate microcapsules suitable for delivery of Cu(II) complex to plants were prepared and characterized. Analysis of the FTIR spectrum showed that complex molecular interactions between functional groups of microcapsule constituents include mainly electrostatic interactions and hydrogen bonds. Microcapsules surface exhibits a soft granular surface structure with substructures consisting of abundant smaller particles with reduced surface roughness. Release profile analysis showed Fickian diffusion is the rate-controlling mechanism of Cu(II) complex releasing. The obtained results give new insights into the complexity of the interaction between the Cu(II) complex and microcapsule formulation constituents, which can be of great help in accelerating product development for the application in agriculture     

Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents

Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC₅₀ value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC₅₀ value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.     

Kinetik der polykondensation von natriumsulfidhydrat und 1,4-dichlorbenzol zu poly(thio-1,4-phenylen)

The kinetics of the polycondensation of sodium sulfide hydrate and 1,4-dichlorobenzene to poly(thio-1,4-phenylene) in 1-methyl-2-pyrrolidone as solvent was studied in a differential scanning calorimeter at temperatures between 220 and 280°C. This polycondensation shows an autocatalytic behavior and the kinetics can be modelled by a first order reaction up to complete conversion. This is explained by the low solubility of sodium sulfide in l-methyl-2-pyrrolidone. The concentration of sodium sulfide is regarded as being constant during the whole course of the reaction. The autocatalytic effect can be explained by the increase of the condensation rate constant at the beginning of polycondensation due to the higher reactivity of the oligomers compared to the monomers. The number- and the weight-average molecular weight of the products formed during the course of the polycondensation can be modelled by means of stochastic methods. A simple model with only two different rate constants of the condensation process is assumed. The concentration of sodium sulfide in the reactive phase is found to be 2–5% of the value of dichlorobenzene at the beginning of the reaction and remains constant nearly until the end of polycondensation.     

Production and Emulsifying Effect of Polyglycerol and Fatty Acid Esters with Varying Degrees of Esterification

Esters with acyl groups can be formed by the esterification of polyglycerol. The purpose of the present study was to produce fatty acid esters [hexanoic (caproic), octanoic (caprylic), decanoic (capric), dodecanoic (lauric), tetradecanoic (myristic), hexadecanoic (palmitic), octadecanoic (stearic)] and polyglycerol (average number‐of degrees of polymerization of 5) with varying degrees of esterification and to examine their emulsifying properties. A number of fundamental catalysts of polyglycerol acylation reactions by methyl esters of carboxylic acid were studied, and sodium methoxide was found to be the best choice. The temperature rate of transesterification increased from 180 to 220 °C with the fatty acid chain alkyl residue. Synthesized mono‐, di‐, tri‐, tetra‐, and heptaesters of various fatty acids and polyglycerol provided the highest hydroxyl values from 15 to 815 mg KOH g^?1 and saponification values from 82 to 321 mg KOH g^?1. The emulsifying properties were assessed for all polyglycerol and fatty acid esters, with results showing maximum emulsifying effect for tri‐ and tetraesters of capric, lauric, and caprylic acids. Regardless of the hydrophilic–lipophilic balance value (HLB) of polyglycerol esters and carboxylic acid, a 4:1 ratio of sunflower oil to water formed a water‐in‐oil type emulsion. When mixing oil and water in a 1:1 ratio, mono‐ and diesters of polyglycerol formed an oil‐in‐water type emulsion, heptaesters formed a water‐in‐oil type emulsion, and tri‐ and tetraesters formed both of types of emulsions, depending on the length of the acid hydrocarbon radicals.     

Development of a multifunctional coating system for laser-induced material transport

The aim of our research is to develop a novel surface coating for the use in laser microdissection and laser pressure catapulting (LMPC). LMPC is a contact- and contamination-free technique to separate histologic material and living cells for further proteomic and genomic analysis. Several physico-chemical functions must be included within the optimum coating system designed for this purpose, like optical absorption at the laser wavelength, combined with optical transparency in the visible region, a control of the laser ablation process, mechanical stability and biocompability for the adhesion of the histologic material.To achieve the optimum system the combination of several layers is required. The optical absorbance to capture the radiation energy from a frequency-tripled Nd:YAG laser (λ = 355 nm) is reached by a thin layer of zinc oxide (ZnO), deposited by hollow cathode gas flow sputtering. The laser ablation process is controlled by a polyelectrolyte multilayer, consisting of poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium 4-styrenesulfonate) (PSS). The evaporation of chemisorbed water from the film is used to promote the catapulting process. For the mechanically stable, laser-dissectible layer organic coatings, like photoresists or lacquers, are suitable. Silica-containing polyacrylate nanocomposites were employed for this purpose.The investigation of the coating system included LMPC experiments with varying compositions of the layer system. The best results were obtained using a system consisting of ZnO, a polyelectrolyte multilayer deposited from 0.1 M Na₂SO₄ containing polymer solutions, and a 1.5-μm thick layer of the polyacrylate nanocomposite.To check the quality of the developed system, experiments with the commonly used poly(ethylene naphthalate) (PEN) foil were performed simultaneously. In addition to the determination of the parameters required for LMPC, quantitative real-time Polymerase Chain Reaction (rt-PCR) of the dissected material verified the benefit of the new system.     

The development and evaluation of the Harm Reduction Self-Efficacy Questionnaire.

The authors recruited 99 injection drug users to assess the psychometric properties of a new self-report questionnaire--the Harm Reduction Self-Efficacy Questionnaire (HRSEQ)--designed to measure injection drug users' confidence to employ 15 specific health-preserving coping skills in different types of high-risk situations (experiencing withdrawal, feeling depressed, and feeling social pressure to use drugs unsafely). Scores for each high-risk situation had good internal consistency (αs = .89 -.92) and good 1-week test-retest reliability (rs = .70 -.85). Comparison with measures of drug-related problems, use of coping skills, and health self-efficacy supported both construct and discriminant validity of the HRSEQ. Exploratory factor analyses revealed 3 major themes (cleanliness precautions, overdose precautions, and safer injection practices) that summarized most, but not all, of the 15 items. Mean differences among the 3 situations suggest that harm reduction self-efficacy should be assessed in the context of specific high-risk situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in liquid‐holding capacity,water distribution and microstructure during chill storage of smoked salmon

BACKGROUND: During recent years, increases in liquid loss and soft texture in cold smoked salmon have been reported, possibly due to increased lipid content and a change in muscle structure. These problems can lead to downgrading of the product. This study aimed to investigate the influence of raw material composition and chill storage on quality parameters of cold smoked salmon. RESULTS: Initial smoked fish had a higher liquid‐holding capacity (LHC) than samples stored for 20 days. Large fish lost more liquid than small fish. The difference in LHC was consistent with a change in water distribution, which could indicate denaturation of muscle protein. Studies of the microstructure showed the influence of both processing and chill storage. An indication of lipid released from the cells was seen after 20 days of chill storage, which could be related to the reduced LHC at that time. CONCLUSION: Both raw material composition and chill storage affected the quality parameters of smoked salmon. This study has improved knowledge about the relationships between muscle structure, liquid‐holding properties and water distribution in smoked salmon. Copyright © 2007 Society of Chemical Industry