Intestinal Disorder in Zebrafish Larvae (Danio rerio): The Protective Action of N-Palmitoylethanolamide-oxazoline

IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to induce enterocolitis and study the protective action of PEAOXA. After repetitive exposure with 0.25% DSS, larvae presented gut alteration with an increase in mucus production. Furthermore, DSS exposure induced an increase in the inflammatory pathway in the intestine, related to an increase in the Endoplasmic-reticulum (ER) stress genes. PEAOXA exposure at a concentration of 10 mg/L decreased the DSS-induced gut damage and mucus production, as well as being able to reduce the inflammatory and ER stress-related genes expression. In conclusion, our results demonstrate that the alterations induced by repeated exposure to DSS were counteracted by PEAOXA action that was able to inhibit the increase in inflammation and ER stress involved in the progression of enterocolitis.

Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc−/−) and their wild type (Hdc+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc−/−and Hdc+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc+/+ mice as histamine deficiency prevented almost all of the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.

Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom

Varespladib (VPL) was primarily developed to treat inflammatory disturbances associated with high levels of serum phospholipase A2 (PLA2). VPL has also demonstrated to be a potential antivenom support agent to prevent PLA2-dependent effects produced by snake venoms. In this study, we examined the action of VPL on the coagulant, haemorrhagic and enzymatic activities of Lachesis muta rhombeata (South-American bushmaster) venom. Conventional colorimetric enzymatic assays were performed for PLA2, caseinolytic and esterasic activities; in vitro coagulant activities for prothrombin time (PT) and activated partial thromboplastin time (aPTT) were performed in rat citrated plasma through a quick timer coagulometer, whereas the dimensions of haemorrhagic haloes obtained after i.d. injections of venom in Wistar rats were determined using ImageJ software. Venom (1 mg/ml) exhibited accentuated enzymatic activities for proteases and PLA2in vitro, with VPL abolishing the PLA2 activity from 0.01 mM; VPL did not affect caseinolytic and esterasic activities at any tested concentrations (0.001–1 mM). In rat citrated plasma in vitro, VPL (1 mM) alone efficiently prevented the venom (1 mg/ml)-induced procoagulant disorder associated to extrinsic (PT) pathway, whereas its association with a commercial antivenom successfully prevented changes in both intrinsic (aPTT) and extrinsic (PT) pathways; commercial antivenom by itself failed to avoid the procoagulant disorders by this venom. Venom (0.5 mg/kg)-induced hemorrhagic activity was slightly reduced by VPL (1 mM) alone or combined with antivenom (antivenom:venom ratio 1:3 ‘v/w’) in rats, with antivenom alone producing no protective action on this parameter. In conclusion, VPL does not inhibit other major enzymatic groups of L. m. rhombeata venom, with its high PLA2 antagonize activity efficaciously preventing the venom-induced coagulation disturbances.

BML-257, a small molecule that protects against drug induced liver injury in zebrafish

The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug induced liver injury (DILI) would be valuable in such situations. We used hepatocyte-specific expression of bacterial nitroreductase in zebrafish to cause temporally controlled liver damage. This transgenic line was used to run a whole organism based chemical screen in zebrafish larvae. In this screen we identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 also showed remarkable protective action in two independent toxicological models of liver injury caused by acetaminophen and Isoniazid. This suggests that BML-257 may have the potential to protect against multiple kinds of drug induced liver injury.

Hypolipidemia activity testing protocol or Guizotia Abyssinica Cass. seed oil: An Experimental study report

Hyperlipidemia is characterized by increased level of cholesterol in the form of low-density lipoprotein (LDL), chylomicrons, VLDL. Guizotia abyssinica Cass (Ramtil) seeds are one among the sources for the edible oil, which are low in saturated fat, cultivated commonly in Northern part of Karnataka. Materials and Methods: Guizotia abyssinica Cass (Ramtil) seeds were collected authenticated seed oil extracted by Cold compression method. The experiment carried out in Wistar albino rats, inducing Hyperlipidemia by HFD, along with administration of test drugs (Guizotia abyssinica Cass. seed oil Single and double dose) and Standard Atorvastatin. Results & Discussion: G. abyssinica Cass seed oil found to decrease total cholesterol and LDL. Even not showed significant increase in HDL. Protective action over the Liver, Kidney and heart through histopathological study exhibit its safety aspect. Conclusion: G. abyssinica Cass seed oil in HFD induced Hyperlipidemia found effective and safe.

Efficacy and Usefulness of an Independent Public Earthquake Early Warning System: A Case Study—The Earthquake Network Initiative in Peru

Public earthquake early warning (PEEW) systems are intended to reduce individual risk by warning people ahead of shaking and allowing them to take protective action. Yet very few studies have assessed their actual efficacy from a risk-reduction perspective. Moreover, according to these studies, a majority of people do not undertake safety actions when receiving the warning. The spectrum of PEEW systems has expanded, with a greater diversity of actors (from citizens to private companies), increased independence from national authorities, and greater internationality. Beyond differences in warning and messaging strategies, systems’ characteristics may impact the way the public perceive, trust, understand, and respond to these warnings, which in turn will influence PEEW systems’ efficacy and perceived usefulness, enhancing the need for additional research. We take the example of earthquake network, an independent, voluntary, community-based and free system that offers a PEEW service. Through a quantitative survey (n = 2625), we studied users’ perception and reaction to a warning sent related to an M 8.0 earthquake in Peru (where no national system existed). We observed that even though only a minority of users actually took protective action, the system was appreciated and perceived as useful by the majority because it enabled mental preparation before the shaking. We found evidence for a tolerance for perceived late, missed, and false alerts. However, because it is a voluntary and independent system, the social dimension of the warning was incomplete because only a fringe of the population benefited from the warning. Therefore, many users’ first reaction was to warn their relatives. We discuss the need for partnerships between PEEW operators and national authorities to guarantee universal access to the service and maximize PEEW system efficacy.

Investigation of the influence of operational factors on the heat-protective characteristics of a package of materials for firefighter combat clothing

The article is devoted to the assessment of the impact of operational factors on the heat-protective performance of a package of materials of firefighter's combat clothing. The paper considers the influence of high humidity, compression of a package of materials, the presence of reflective elements in a package of clothing materials. The operational factors of influence on the heat-protective indicators of the package of materials of the firefighter's combat clothing, which reduce the protective action time by more than 3 times, are determined. The paper notes that it is the humidity and compression of the package of materials that change the nature of heating, which is due to an increase in the thermal conductivity of the layers when these factors affect the porous material.