Synthesis and Characterization of New Bivalent Agents as Melatonin- and Histamine H3-Ligands

Melatonin is an endogenous molecule involved in many pathophysiological processes. In addition to the control of circadian rhythms, its antioxidant and neuroprotective properties have been widely described. Thus far, different bivalent compounds composed by a melatonin molecule linked to another neuroprotective agent were synthesized and tested for their ability to block neurodegenerative processes in vitro and in vivo. To identify a novel class of potential neuroprotective compounds, we prepared a series of bivalent ligands, in which a prototypic melatonergic ligand is connected to an imidazole-based H₃ receptor antagonist through a flexible linker. Four imidazolyl-alkyloxy-anilinoethylamide derivatives, characterized by linkers of different length, were synthesized and their binding affinity for human MT₁, MT₂ and H₃ receptor subtypes was evaluated. Among the tested compounds, 14c and 14d, bearing a pentyl and a hexyl linker, respectively, were able to bind to all receptor subtypes at micromolar concentrations and represent the first bivalent melatonergic/histaminergic ligands reported so far. These preliminary results, based on binding affinity evaluation, pave the way for the future development of new dual-acting compounds targeting both melatonin and histamine receptors, which could represent promising therapeutic agents for the treatment of neurodegenerative pathologies.     

A rapid high-performance liquid chromatography with fluorescence detection method developed to analyze ochratoxin A in wine

A rapid, sensitive, reproducible, and inexpensive method of high-performance liquid chromatography with fluorescence detection (HPLC-FLD) for the analysis of ochratoxin A (OTA) in wine was developed. It is characterized by direct injection of the wine into the HPLC apparatus, with no need of extraction or cleanup. The method uses acetonitrile, water, and acetic acid (49:49:2, vol/vol/vol, respectively) as the isocratic mobile phase and a 5-microm monolithic C18 column (100 by 3 mm inside diameter). The relative standard deviation obtained in the OTA determination varied between 0.22 and 1.76%, with a mean value of 0.89%, in samples with concentrations between 0.10 and 100 ng/ml. The recovery of OTA ranged from 102% in samples spiked with 1 ng/ml OTA to 120% in samples with 0.10 ng/ml OTA. The method compared favorably with a published method based on an immunoaffinity column cleanup and a chromatographic assay with a C18 conventional HPLC column.     

Milk protein fractions strongly affect the patterns of coagulation,curd firming,and syneresis

The aim of this study was to assess the role of milk protein fractions in the coagulation, curd firming, and syneresis of bovine milk. Analyses were performed on 1,271 individual milk samples from Brown Swiss cows reared in 85 herds classified into 4 types of farming systems, from the very traditional (tied cows, feed manually distributed, summer highland pasture) to the most modern (loose cows, use of total mixed rations with or without silage). Fractions α_S1-casein (CN), α_S2-CN, β-CN, κ-CN, β-lactoglobulin (LG), and α-lactalbumin (LA) and genotypes at CSN2, CSN3, and BLG were obtained by reversed-phase HPLC. The following milk coagulation properties were measured with a lactodynamograph, with the testing time extended to 60 min: rennet coagulation time (RCT, min), curd firming time (min), and curd firmness at 30 and 45 min (mm). All the curd firmness measures recorded over time (total of 240 observations/sample) were used in a 4-parameter nonlinear model to obtain parameters of coagulation, curd firming, and syneresis: RCT estimated from the equation (min), asymptotic potential curd firmness (mm), the curd firming and syneresis instant rate constants (%/min), and the maximum curd firmness value (CF_max, mm) and the time taken to reach it (min). All the aforementioned traits were analyzed with 2 linear mixed models, which tested the effects of the protein fractions expressed in different ways: in the first, quantitative model, each protein fraction was expressed as content in milk; in the second, qualitative model, each protein fraction was expressed as a percentage of total casein content. Besides proteins, additional nuisance parameters were herd (included as a random effect), daily milk production (only for the quantitative model), casein content (only for the qualitative model), dairy system, parity, days in milk, the pendulum of the lactodynamograph, and the CSN2, CSN3, and BLG genotypes. Both α_S1-CN and β-CN showed a clear and favorable effect on CF_max, where the former effect was almost double the latter. Milk coagulation ability was favorably affected by κ-CN, which reduced both the RCT and RCT estimated from the equation, increased the curd firming and syneresis instant rate constants, and allowed a higher CF_max to be reached. In contrast, α_S2-CN delayed gelation time and β-LG worsened curd firming, both resulting in a low CF_max. The results of this study suggest that modification of the relative contents of specific protein fractions can have an enormous effect on the technological behavior of bovine milk.     

Genetic variation in serum protein pattern and blood β-hydroxybutyrate and their relationships with udder health traits,protein profile,and cheese-making properties in Holstein cows

The aim of this study was to investigate in Holstein cows the genetic basis of blood serum metabolites [i.e., total protein, albumin, globulin, albumin:globulin ratio (A:G), and blood β-hydroxybutyrate (BHB)], a set of milk phenotypes related to udder health, milk quality technological characteristics, and genetic relationships among them. Samples of milk were collected from 498 Holstein cows belonging to 28 herds. All animal welfare and milk phenotypes were assessed using standard analytical methodology. A set of Bayesian univariate and bivariate animal models was implemented via Gibbs sampling, and statistical inference was based on the marginal posterior distributions of parameters of concern. We observed a small additive genetic influence for serum albumin concentrations, moderate heritability (≥0.20) for total proteins, globulins, and A:G, and high heritability (0.37) for blood BHB. Udder health traits (somatic cell score, milk lactose, and milk pH) showed low or moderate heritabilities (0.15–0.20), whereas variations in milk protein fraction concentrations were confirmed as mostly under genetic control (heritability: 0.21–0.71). The moderate and high heritabilities observed for milk coagulation properties and curd firming modeling parameters provided confirmation that genetic background exerts a strong influence on the cheese-making ability of milk, largely due to genetic polymorphisms in the major milk protein genes. Blood BHB showed strong negative genetic correlations with globulins (?0.619) but positive correlations with serum albumin (0.629) and A:G (0.717), which suggests that alterations in the serum protein pattern and BHB blood levels are likely to be genetically related. Strong relationships were found between albumin and fat percentages (?0.894), between globulin and α_S2-CN (?0.610), and, to a lesser extent, between serum protein pattern and milk technological characteristics. Genetic relationships between blood BHB and traits related to udder health and milk quality and technological characteristics were mostly weak. This study provides evidence that there is exploitable additive genetic variation for traits related to animal health and welfare and throws light on the shared genetic basis of these traits and the phenotypes related to the quality and cheese-making ability of milk.     

Dairy system,parity, and lactation stage affect enteric methane production,yield, and intensity per kilogram of milk and cheese predicted from gas chromatography fatty acids

Ruminants (and milk production) contribute to global climate change through enteric methane emissions (EME), and any attempt to reduce them is complicated by the fact that they are difficult and expensive to measure directly. In the case of dairy cows, a promising indirect method of estimating EME is to use the milk fatty acid profile as a proxy, as a relationship exists between microbial activity in the rumen and the molecules available for milk synthesis in the mammary gland. In the present study, we analyzed the detailed fatty acid profiles (through gas chromatography) of a large number of milk samples from 1,158 Brown Swiss cows reared on 85 farms with the aim of testing in the field 2 equations for estimating EME taken from a published meta-analysis. The average estimated methane yield (CH₄ emission per kg of dry matter intake, 21.34 ± 1.60 g/kg) and methane intensity (per kg of corrected milk, 14.17 ± 1.78 g/kg), and the derived methane production (CH₄ emissions per day per cow, 357 ± 109 g/d) were similar to those previously published. Using data from model cheese makings from individual cows, we also calculated estimated methane intensity per kilogram of fresh cheese (99.7 ± 16.4 g/kg) and cheese solids (207.5 ± 30.9 g/kg). Dairy system affected all EME estimates. Traditional dairy farms, and modern farms including corn silage in the TMR exhibited greater estimated methane intensities. We found very wide variability in estimated EME traits among different farms within dairy system (0.33 to 0.61 of total variance), suggesting the need to modify the farms' feeding regimens and management practices to mitigate emissions. Among the individual factors, parity order affected all estimated EME traits excepted methane yield, with an increase from first lactation to the following ones. Lactation stage exhibited more favorable estimated EME traits during early lactation, concomitant with the availability of nutrients from body tissue mobilization for mammary synthesis of milk. Our results showed a coherence between the EME traits estimated from the analysis of milk fatty acids and the expectations according to current knowledge. Further research is needed to validate the results obtained in this study in other breeds and populations, to assess the magnitude of the genetic variation and the potential of these phenotypes to be exploited in breeding programs with the aim to mitigate emissions.     

Non‐Celiac Gluten Sensitivity: How Its Gut Immune Activation and Potential Dietary Management Differ from Celiac Disease

Non‐celiac gluten sensitivity (NCGS) is a clinical entity triggered by the ingestion of gluten‐containing grains leading to intestinal and/or extraintestinal symptoms that resolve once the gluten‐containing foodstuff is eliminated from the diet, and it is diagnosed when celiac disease (CD) and wheat allergy (WA) have been ruled out. The limited knowledge about the pathophysiology of NCGS and the lack of validated biomarkers are still major limitations for clinical studies, making it difficult to differentiate NCGS from other gluten‐related disorders (GRD). In the absence of clear‐cut diagnostic criteria, NCGS is still mainly a diagnosis of exclusion. Several studies suggest that NCGS is an immune‐mediated disease that likely activates an innate immune response. Moreover, it has recently been hypothesized that in addition to gluten, other components of wheat may be responsible for the symptoms observed in individuals without CD. This review aims at discussing available evidence related to the histological and immunological features in the gut mucosa of patients with NCGS and at outlining new dietary opportunities for these patients.     

Parenting and antisocial behavior: A model of the relationship between adolescent self-disclosure, parental closeness, parental control, and adolescent antisocial behavior.

This study used data collected from a sample of 840 Italian adolescents (418 boys; M age = 12.58) and their parents (657 mothers; M age = 43.78) to explore the relations between parenting, adolescent self-disclosure, and antisocial behavior. In the hypothesized model, parenting practices (e.g., parental monitoring and control) have direct effects on parental knowledge and antisocial behavior. Parenting style (e.g., parent–child closeness), on the other hand, is directly related to adolescent self-disclosure, which in turn is positively related to parental knowledge and negatively related to adolescents’ antisocial behavior. A structural equation model, which incorporated data from parents and adolescents, largely supported the hypothesized model. Gender-specific models also found some gender differences among adolescents and parents, as the hypothesized model adequately fit the subsample of mothers but not fathers. Mothers’ closeness to girls predicted their knowledge of their daughters’ behavior; mothers’ control predicted boys’ antisocial behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Kinetic modeling study of ethanol and dimethyl ether addition to premixed low-pressure propene–oxygen–argon flames

The chemical composition of flames of mixed hydrocarbon–oxygenate fuels was examined systematically for a series of laminar, premixed low-pressure propene–oxygen–argon flames blended with ethanol or dimethyl ether (DME). All flames were established at a carbon-to-oxygen ratio of C/O = 0.5 at 40 mbar. Propene was replaced incrementally by either additive, so that the entire range from pure propene to pure ethanol or pure DME was accessible. Experimental results have been reported previously (J. Wang et al., J. Chem. Phys. A 112 (2008) 9255–9265), including temperature profiles measured with laser-induced fluorescence (LIF) and quantitative mole fraction profiles for a large number of species obtained from molecular-beam mass spectrometry (MBMS), using electron ionization (EI) and vacuum-ultraviolet (VUV) photoionization (PI). The effects of oxygenate addition to the propene base flame were seen to result in interesting differences, especially regarding trends to form aldehydes. The entire flame series is now analyzed with a comprehensive kinetic model that combines the chemistries of propene, ethanol, and DME combustion. The flames of pure fuels are also compared with the predictions of different detailed mechanisms taken from the literature. Quantitative comparison of C₁- to C₆-species from this model with the measurements is provided. Major trends of propene replacement by the oxygenates are reproduced in quantitative agreement with the experiments, enabling a more detailed understanding of the combined reaction sequences in such fuel blends.