The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats

Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.     

The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats

A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.     

Effect of natural biostimulants on yield and nutritional quality: an example of sweet yellow pepper (Capsicum annuum L.) plants

BACKGROUND: Modifications in growing techniques can affect the yield and nutritional quality of various cultivated plant species. Owing to its high nutritional value, pepper (Capsicum annuum L.) was used in this study as a model plant to investigate the effect of natural biostimulants on yield and fruit quality parameters under conditions of reduced fertilisation. RESULTS: A positive influence of biostimulant treatment on yield parameters was observed. The overall increase in the pigment content of leaves after biostimulant application agreed well with the higher total and commercial yields of treated pepper cultivars compared with their controls. The results showed that natural biostimulants had a positive effect on the vitamin C and total phenolic contents in pepper fruits during the hot summer season. The 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonate) (ABTS) antioxidant activities were also significantly higher (P < 0.05) in treated plants and correlated strongly with all measured quality parameters except total phenolic content. CONCLUSION: Generally, biostimulants improved the antioxidant activity, vitamin C and phenolic contents in fruits as well as the pigment content in leaves of treated compared with non‐treated pepper plants grown hydroponically. Thus the application of biostimulants could be considered as a good production strategy for obtaining high yields of nutritionally valuable vegetables with lower impact on the environment. Copyright © 2011 Society of Chemical Industry     

Mechanism of action of tubulysin, an antimitotic peptide from myxobacteria

Tubulysin A is a highly cytotoxic peptide with antimitotic activity that induces depletion of cell microtubules and triggers the apoptotic process. Treated cells accumulated in the G2/M phase. Tubulysin A inhibited tubulin polymerization more efficiently than vinblastine and induced depolymerization of isolated microtubule preparations. Microtubule depolymerization could not be prevented by preincubation with epothilone B and paclitaxel, neither in cell-free systems nor in cell lines. In competition experiments, tubulysin A strongly interfered with the binding of vinblastine to tubulin in a noncompetitive way; the apparent Ki was 3 microM. Electron microscopy investigations showed that tubulysin A induced the formation of rings, double rings, and pinwheel structures. The mode of action of tubulysin A resembled that of peptide antimitotics dolastatin 10, phomopsin A, and hemiasterlin. Efforts are underway to develop this new group of compounds as anticancer drugs.     

Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection

Canine babesiosis is an important tick-borne disease worldwide, caused by parasites of the Babesia genus. Although the disease process primarily affects erythrocytes, it may also have multisystemic consequences. The goal of this study was to explore and characterize the serum metabolome, by identifying potential metabolites and metabolic pathways in dogs naturally infected with Babesia canis using liquid and gas chromatography coupled to mass spectrometry. The study included 12 dogs naturally infected with B. canis and 12 healthy dogs. By combining three different analytical platforms using untargeted and targeted approaches, 295 metabolites were detected. The untargeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) metabolomics approach identified 64 metabolites, the targeted UHPLC-MS/MS metabolomics approach identified 205 metabolites, and the GC-MS metabolomics approach identified 26 metabolites. Biological functions of differentially abundant metabolites indicate the involvement of various pathways in canine babesiosis including the following: glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis. This study confirmed that host–pathogen interactions could be studied by metabolomics to assess chemical changes in the host, such that the differences in serum metabolome between dogs with B. canis infection and healthy dogs can be detected with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Our study provides novel insight into pathophysiological mechanisms of B. canis infection.     

Comparison of 2-D and 3-D computer models for the M. Salta rock fall, Vajont Valley, northern Italy

A rock fall occurs when a fragment of rock is detached from a cliff and travels down-slope at high speed. Rock falls are a constant hazard in mountainous regions and pose a significant threat to the population. In this paper, a comparison of software designed to model rock falls is presented. The computer codes selected for the experiment are STONE and RocFall®. STONE is a research code for the 3-dimensional simulation of rock falls. RocFall® is commercial software widely used for the 2-dimensional simulation of rock falls along user defined topographic profiles. The two computer programs require similar input and provide comparable outputs, allowing for a quantitative evaluation of their modelling results. To compare the software, the Monte Salta rock fall, in northern Italy, was selected. Specific tests were designed to compare the ability of the software to predict the maximum travel distance of the falling boulders, and the distance from the ground of the computed rock fall trajectories. Results indicate that the two rock fall modelling codes provide similar—but not identical—results. In general, STONE computes higher and longer rock fall trajectories than RocFall®, and allows identifying a larger area as potentially affected by falling boulders.     

Small convolution kernels for high-fidelity image restoration

An algorithm is developed for computing the mean-square-optimal values for small, image-restoration kernels. The algorithm is based on a comprehensive, end-to-end imaging system model that accounts for the important components of the imaging process: the statistics of the scene, the point-spread function of the image-gathering device, sampling effects, noise, and display reconstruction. Subject to constraints on the spatial support of the kernel, the algorithm generates the kernel values that restore the image with maximum fidelity, that is, the kernel minimizes the expected mean-square restoration error. The algorithm is consistent with the derivation of the spatially unconstrained Wiener filter, but leads to a small, spatially constrained kernel that, unlike the unconstrained filter, can be efficiently implemented by convolution. Simulation experiments demonstrate that for a wide range of imaging systems these small kernels can restore images with fidelity comparable to images restored with the unconstrained Wiener filter     

Multi-objective optimization of steel AISI 1040 dry turning using genetic algorithm

Neural Computing and Applications - This study investigated the AISI 1040 steel turning in dry environment with four cutting inserts of different corner radii coated by CVD method. Experimental...     

5G Emerging and Mission Critical Framework with Ultra‐Reliable Low Delay

Wireless Personal Communications - This paper presents a new user-centric approach in establishing reliable communication for mission and time-critical data, being able to use multiple available...