Beneficial Effect of Melatonin Alone or in Combination with Glatiramer Acetate and Interferon ß-1b on Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon ß-1b (IFNß-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNß-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNß-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.

Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson's Disease.

Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson's disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.

Heats of combustion of the main carbohydrates contained in plant-source foods.

In a previous review, the experiments of American chemist W.O. Atwater were critically examined, with the findings demonstrating certain weaknesses that could compromise the validity of the values currently used for metabolizable energy. An examination of published works on the heat of combustion of carbohydrates reveals 2 types of weaknesses: the inaccuracy and imprecision of the calorimetric data used, and the averaging procedure employed to estimate such representative values. The present review focuses on the first type of weakness, namely the inaccuracy and imprecision of the calorimetric data used in previous studies. An exhaustive bibliographic search yielded almost 100 heat of combustion values for some of the 6 main carbohydrates contained in plant-source foods (glucose, fructose, sucrose, maltose, starch, and cellulose). These heats of combustion were subjected to rigorous statistical analysis to propose the following for each carbohydrate: (1) an interval (termed a bibliographic interval) that very likely includes the actual heat of combustion value and (2) a "representative value" (calculated to produce the minimum level of inaccuracy). In addition, an estimation of the maximum level of inaccuracy that could be expected when using such a representative value is reported.

Heats of combustion representative of the carbohydrate mass contained in fruits, vegetables, or cereals.

The obtainment of suitable values for metabolizable energy requires the previous knowledge of accurate and precise values of the heat of combustion of the different macronutrients. Thus, in this work, the heats of combustion of six carbohydrates (glucose, fructose, sucrose, maltose, starch, and cellulose) were experimentally measured, and such values were statistically compared with equivalent bibliographic values collected in a parallel work (Heats of combustion of the main carbohydrates in vegetable foods: a bibliographic approach, 2019), proposing, for each carbohydrate, an "overall interval" and an actualized representative value, which were estimated considering jointly the bibliographic and experimental information. Besides, a numerical methodology that used such parameters and the relative content of the different carbohydrates in selected foods was proposed, to estimate the global heat of combustion producible by the carbohydrate mass contained in such foods. The results estimated for 68 foods were globalized to propose the following generalized heats of combustion: (a) for fruits: 3.88 kcal/g, (b) for vegetables: 3.98 kcal/g and, and (c) for cereals: 4.13 kcal/g. These results demonstrated that the use of the Atwater's value (4.2 kcal/g of carbohydrate of vegetable source) involves a clear overestimation of the heat of combustion of the carbohydrate mass contained in vegetable source foods.

Two-Dimensional Thin Layer Chromatography-Bioautography Designed to Separate and Locate Metabolites with Antioxidant Activity Contained on Spirulina platensis.

Spirulina platensis contains several biologically active compounds, some of them with antioxidant activity. Nevertheless, not all of these compounds have been identified to date. As a first step to achieving such identification, a methodology to perform two-dimensional thin layer chromatography bioautographies on silica gel thin layer chromatography plates was proposed. Starting with a reference binary system, 5 other binary systems were tested, in which the relative polarity was systematically increased. To further improve the separation behavior, a phase modifier (NH4OH) was used. The best separation results were obtained with the isopropyl alcohol/ethyl acetate/NH4OH ternary system. This experimental system allowed four well-resolved spots showing antioxidant activity as well as two additional areas with mixtures containing antioxidant compounds. Although the proposed methodology was designed with a specific application, it would be predictable that its field of use could be considerably greater, making the convenient modifications on the solvent polarity and "masking level" produced by the ammonium derivatives.

Tailoring Copolymer Properties by Gradual Changes in the Distribution of the Chains Composition Using Semicontinuous Emulsion Polymerization.

To design the properties of a copolymer using free radical polymerization, a semicontinuous process can be applied to vary the instantaneous copolymer composition along the conversion searching for a specific composition spectrum of copolymer chains, which can be termed as weight composition distribution (WCD) of copolymer chains. Here, the styrene-n-butyl acrylate (S/BA) system was polymerized by means of a semicontinuous emulsion process, varying the composition of the comonomer feed to obtain forced composition copolymers (FCCs). Five different feeding profiles were used, searching for a scheme to obtain chains rich in S (looking for considerable modulus), and chains rich in BA (looking for large deformation) as a technique to achieve synergy in copolymer properties; the mechanostatic and dynamic characterization discloses the correspondence between WCD and the bulk properties. ¹H-nuclear magnetic resonance (¹H-NMR) analysis enabled the determination of the cumulative copolymer composition characterization, required to estimate the WCD. The static test (stress-strain) and dynamic mechanical analysis (DMA) were performed following normed procedures. This is the first report that shows very diverse mechanostatic performances of copolymers obtained using the same chemical system and global comonomer composition, forming a comprehensive failure envelope, even though the tests were carried out at the same temperature and cross head speed. The principles for synergic performance can be applied to controlled radical copolymerization, designing the composition variation in individual molecules along the conversion.