Zebrafish behavioral response to ivermectin: Insights into potential neurological risk

Ivermectin is a well‐known and widely used anti‐parasitic drug. Recently, in vitro data suggest anti‐viral effi- cacy of the drug, albeit at much higher concentrations than currently approved. Despite warnings by several governing bodies, the (uncontrolled) human use of ivermectin has significantly increased during the COVID‐ 19 epidemic. This study thus aimed to elucidate potential neurological risk of particularly the veterinary for- mulation of ivermectin in comparison to pure ivermectin. Zebrafish eggs (1hpf) and larvae (4dpf) were exposed to a range of concentrations of either pure ivermectin (IVM) or a veterinary formulation (V‐IVM) for a period of 24 hours. Behavioral responses to both treatments were assessed at various timepoints using the pentylenete- trazol assay, the light–dark assay and a 5‐day teratogenesis protocol. In addition, dissolution rates were calcu- lated for both treatments

Social media and COVID-19 – perceptions and public deceptions regarding colchicine, hydroxychloroquine and ivermectin and resultant lessons for future pandemics

Background: The capacity for social media to influence the consumption of re-purposed medicines to manage COVID-19 despite limited safety and efficacy data at the start of the pandemic is cause for concern. Objective: To ascertain links between social media reports and utilization for three re-purposed medicines (hydroxychloroquine (HCQ), ivermectin and colchicine) to direct future activities. Methods: A combined retrospective analysis of social media posts for these re-purposed medicines was performed in South Africa between January and June 2021 together with utilization and clinical trials data. Utilisation data from IQVIA from three different platforms included private and public markets. Clinical trials data was obtained from various databases. Chloroquine data was analysed in South Africa (HCQ was not available). Results: 77257 posts were collected across key social media platforms during the study period of which 6884 were relevant. Ivermectin had the highest number of posts (55%) followed by HCQ (44%), with limited posts for colchicine (1%). The spike in ivermectin utilisation was closely correlated with social media posts. Similarly, with chloroquine social media interest was enhanced by comments from local politicians. Sentiment analysis showed that the posts regarding the effectiveness of particularly ivermectin and HCQ were positive. Of concern is that the origin of the majority of reporters in social media (85%) was unidentifiable. Conclusion: This is the first study of its kind in South Africa providing evidence that social media is a driver of re-purposed medicine use. Healthcare professionals have a key role to provide evidence-based advice especially with unidentifiable posts

Social media and COVID-19 – perceptions and public deceptions of ivermectin, colchicine and hydroxychloroquine : lessons for future pandemics

The capacity for social media to influence the utilization of re-purposed medicines to manage COVID-19, despite limited availability of safety and efficacy data, is a cause for concern within health care systems. This study sought to ascertain links between social media reports and utili-zation for three re-purposed medicines: hydroxychloroquine (HCQ), ivermectin and colchicine. A combined retrospective analysis of social media posts for these three re-purposed medicines was undertaken, along with utilization and clinical trials data, in South Africa, between January 2020 and June 2021. In total, 77,257 posts were collected across key social media platforms, of which 6884 were relevant. Ivermectin had the highest number of posts (55%) followed by HCQ (44%). The spike in ivermectin use was closely correlated to social media posts. Similarly, regarding chlo-roquine (as HCQ is not available in South Africa), social media interest was enhanced by local politicians. Sentiment analysis revealed that posts regarding the effectiveness of these repurposed medicines were positive. This was different for colchicine, which contributed only a small number of mentions (1%). Of concern is that the majority of reporters in social media (85%) were uniden-tifiable. This study provides evidence of social media as a driver of re-purposed medicines. Healthcare professionals have a key role in providing evidence-based advice especially with unidentifiable post

How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting

The cytotoxicity of the venom of 25 species of Old World elapid snake was tested and compared with the morphological and behavioural adaptations of hooding and spitting. We determined that, contrary to previous assumptions, the venoms of spitting species are not consistently more cytotoxic than those of closely related non-spitting species. While this correlation between spitting and non-spitting was found among African cobras, it was not present among Asian cobras. On the other hand, a consistent positive correlation was observed between cytotoxicity and utilisation of the defensive hooding display that cobras are famous for. Hooding and spitting are widely regarded as defensive adaptations, but it has hitherto been uncertain whether cytotoxicity serves a defensive purpose or is somehow useful in prey subjugation. The results of this study suggest that cytotoxicity evolved primarily as a defensive innovation and that it has co-evolved twice alongside hooding behavior: once in the Hemachatus + Naja and again independently in the king cobras (Ophiophagus). There was a significant increase of cytotoxicity in the Asian Naja linked to the evolution of bold aposematic hood markings, reinforcing the link between hooding and the evolution of defensive cytotoxic venoms. In parallel, lineages with increased cytotoxicity but lacking bold hood patterns evolved aposematic markers in the form of high contrast body banding. The results also indicate that, secondary to the evolution of venom rich in cytotoxins, spitting has evolved three times independently: once within the African Naja, once within the Asian Naja, and once in the Hemachatus genus. The evolution of cytotoxic venom thus appears to facilitate the evolution of defensive spitting behaviour. In contrast, a secondary loss of cytotoxicity and reduction of the hood occurred in the water cobra Naja annulata, which possesses streamlined neurotoxic venom similar to that of other aquatic elapid snakes (e.g., hydrophiine sea snakes). The results of this study make an important contribution to our growing understanding of the selection pressures shaping the evolution of snake venom and its constituent toxins. The data also aid in elucidating the relationship between these selection pressures and the medical impact of human snakebite in the developing world, as cytotoxic cobras cause considerable morbidity including loss-of-function injuries that result in economic and social burdens in the tropics of Asia and sub-Saharan Africa

Bioavailability of resveratrol : possibilities for enhancement

Resveratrol is a naturally occurring polyphenol that has been shown to elicit a variety of beneficial effects in vitro. Translating these gains to in vivo and clinical settings has proven to be a major challenge, because of its poor oral bioavailability. This caveat was confirmed after reviewing clinical trials conducted on this investigational product over the past two years. This review provides alternative methods of administration of resveratrol which may enhance its bioavailability. However, these methods remain to be validated.http://www.elsevier.com/locate/hermed2019-03-01hj2017Pharmacolog