Immune Modulating Brevetoxins: Monocyte Cytotoxicity,Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups

Brevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. Lower doses, in contrast, have been shown to elicit neuroregeneration. Brevetoxins have thus been proposed as a novel treatment for patients after stroke, when neuron regrowth and repair is critical to recovery. However, findings from environmental exposures indicate that brevetoxins may cause inflammation, thus, there is concern for brevetoxins as a stroke therapy given the potential for neuroinflammation. In this study, we examined the inflammatory properties of several brevetoxin analogs, including those that do and do not bind strongly to VGSCs, as binding has classically indicated toxicity. We found that several analogs are toxic to monocytes, while others are not, and the degree of toxicity is not directly related to VGSC binding. Rather, results indicate that brevetoxins containing aldehyde groups were more likely to cause immunotoxicity, regardless of binding affinity to the VGSC. Our results demonstrate that different brevetoxin family members can elicit a spectrum of apoptosis and necrosis by multiple possible mechanisms of action in monocytes. As such, care should be taken in treating “brevetoxins” as a uniform group, particularly in stroke therapy research.     

Modelling the oceanic habitats of two pelagic species using recreational fisheries data

Defining the oceanic habitats of migratory marine species is important for both single species and ecosystem‐based fisheries management, particularly when the distribution of these habitats vary temporally. This can be achieved using species distribution models that include physical environmental predictors. In the present study, species distribution models that describe the seasonal habitats of two pelagic fish (dolphinfish, Coryphaena hippurus and yellowtail kingfish, Seriola lalandi), are developed using 19 yr of presence‐only data from a recreational angler‐based catch‐and‐release fishing programme. A Poisson point process model within a generalized additive modelling framework was used to determine the species distributions off the east coast of Australia as a function of several oceanographic covariates. This modelling framework uses presence‐only data to determine the intensity of fish (fish km^?2), rather than a probability of fish presence. Sea surface temperature (SST), sea level anomaly, SST frontal index and eddy kinetic energy were significant environmental predictors for both dolphinfish and kingfish distributions. Models for both species indicate a greater fish intensity off the east Australian coast during summer and autumn in response to the regional oceanography, namely shelf incursions by the East Australian Current. This study provides a framework for using presence‐only recreational fisheries data to create species distribution models that can contribute to the future dynamic spatial management of pelagic fisheries.     

In vivo screening of subcutaneous tolerability for the development of novel excipients

To develop safe subcutaneous formulations and minimize the risk of local irritation, it is essential to optimize the composition of active pharmaceutical ingredients and excipients. Depending on the physicochemical properties of the active pharmaceutical ingredient, additional excipients may be required to improve the stability and solubility of the active pharmaceutical ingredient. However, some of these excipients may not have been previously used in injectable drugs. Owing to the lack of safety data for such excipients, especially those used in subcutaneous dosing, it is important to evaluate their potential for local irritation during the early stages of formulation development. We evaluated the tolerability of 44 formulations with 24 candidate novel excipients, such as surfactants, polymers, and lipids, in a single subcutaneous dose in rats. Excipient formulations were administered as single bolus subcutaneous injections with an injection volume of 1 mL. The injection sites were observed for 2 days, and macroscopic and microscopic examinations were conducted. Local tolerability was evaluated on the basis of severity, incidence, and pathophysiology of each finding. Formulations that caused tissue degeneration or necrosis, which is indicative of tissue injury, were determined to be irritative and poorly tolerated. A single-dose subcutaneous screening study in rats was considered effective in ranking the safety of candidate excipients during the formulation optimization phase.     

Environmental drivers of yellowtail kingfish,Seriola lalandi,activity inferred through a continental acoustic tracking network

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