Sinus venous thrombosis as a complication of COVID-19-associated hypercoagulability

Sinus venous thrombosis (SVT) is an increasingly recognised complication of not only SARS-CoV-2 infections, but also of SARS-CoV-2 vaccinations. SVT is attributed to hypercoagulability, a common complication of COVID-19, disregarding the severity of the infection. Hypercoagulability in COVID-19 is explained by direct activation of platelets, enhancing coagulation, by direct infection and indirect activation of endothelial cells by SARS-CoV-2, shifting endothelial cells from an anti-thrombotic to a pro-thrombotic state, by direct activation of complement pathways, promoting thrombin generation, or by immune thrombocytopenia, which also generates a thrombogenic state. Since SVT may occur even in anticoagulated COVID-19 patients and may have an unfavourable outcome, all efforts must be made to prevent this complication or to treat it accurately.

Possible mechanisms of action of cannabidiol in the epilepsies: a review

Background: Cannabidiol (CBD) is a compound of Cannabis Sativa plant that has been studied since the 1970s for its effectiveness in the treatment of refractory epilepsies. With the discovery of the endocannabinoid system, most recent studies have been dedicated to elucidating its mechanisms of action. Objective: To review scientific articles in order to enlightening the antiepileptic cannabidiol’s mechanisms of action. Methods: Literature review on both PubMed and Google Scholar searching for the terms: “epilepsy”, “cannabidiol” and “mechanism of action”. Results: We found that cannabidiol has a lot of mechanisms of action which can explain its effectiveness, among which stand out: endocannabinoid system facilitation, by inhibition of recaption and hydrolysis of anandamide as well as by the facilitation of its synthesis and release. These processes must result in the indirect activation of CB1 and CB2 receptors. Furthermore, CBD promotes the activation of mTOR and PI3K proteins intracellular pathway, with subsequent reduction of glutamatergic release. Conclusions: The general hypothesis is that cannabidiol has antiepileptic effectiveness, even in cases of refractory epilepsies, precisely for showing several mechanisms of action. We emphasize, however, the necessity of more researches in this area for further enlightenment of theses possible mechanisms of action and the applicability in the treatment of epilepsies.

The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved?

Bax and Bak, two functionally similar, pro-apoptotic proteins of the Bcl-2 family, are known as the gateway to apoptosis because of their requisite roles as effectors of mitochondrial outer membrane permeabilization (MOMP), a major step during mitochondria-dependent apoptosis. The mechanism of how cells turn Bax/Bak from inert molecules into fully active and lethal effectors had long been the focal point of a major debate centered around two competing, but not mutually exclusive, models: direct activation and indirect activation. After intensive research efforts for over two decades, it is now widely accepted that to initiate apoptosis, some of the BH3-only proteins, a subclass of the Bcl-2 family, directly engage Bax/Bak to trigger their conformational transformation and activation. However, a series of recent discoveries, using previously unavailable CRISPR-engineered cell systems, challenge the basic premise that undergirds the consensus and provide evidence for a novel and surprisingly simple model of Bax/Bak activation: the membrane (lipids)-mediated spontaneous model. This review will discuss the evidence, rationale, significance, and implications of this new model.

Persistent Tachycardia in a Patient on Clozapine

Tachycardia emergent from clozapine treatment is usually transient, often missed, unreported, and therefore frequently goes untreated resulting in possible premature discontinuation of an otherwise effective treatment. Clozapine-induced tachycardia results from direct effects on the sympathetic nervous system including the blockade of cardiac muscarinic M2 receptors, presynaptic α2 adrenoceptors, and indirect activation of the β adrenoceptors. Unfortunately, there are no clear guidelines for monitoring or treating tachycardia induced by clozapine. We present a case of a 55-year-old man with treatment-resistant schizophrenia initiated on clozapine who developed persistent tachycardia and right bundle branch block in the course of treatment. Tachycardia persisted despite treatment with metoprolol and necessitated a transfer to the intensive care unit. A reduction in clozapine dose with the addition of adjunctive antipsychotic(lurasidone) stabilized the patient’s heart rate. This case highlights the need for consistent physical examination and a multidisciplinary-based treatment approach for patients on clozapine. The case also suggests that clozapine dose reduction and combination antipsychotic treatments may preclude the need to discontinue clozapine in patients with persistent tachycardia.

WRKY10 transcriptional regulatory cascades in rice are involved in basal defense and Xa1-mediated resistance

WRKY proteins play essential roles as negative or positive regulators of pathogen defense. This study explored the roles of different OsWRKY proteins in basal defense and Xa1-mediated resistance to Xanthomonas oryzae pv. oryzae (Xoo) infection in rice. Assays of disease in OsWRKY10KD and OsWRKY88KD lines following infection with an incompatible Xoo race, which induced Xa1-mediated resistance in wild-type plants, showed that OsWRKY10 and OsWRKY88 were positive regulators of Xa1-mediated resistance. OsWRKY10 also acted as a positive regulator in basal defense by directly or indirectly activating transcription of defense-related genes. OsWRKY10 activated the OsPR1a promoter by binding to specific WRKY binding sites. Two transcriptional regulatory cascades of OsWRKY10 were identified in basal defense and Xa1-mediated resistance. In the first transcriptional regulatory cascade, OsWRKY47 acted downstream of OsWRKY10 whereas OsWRKY51 acted upstream. OsWRKY10 activated OsPR1a in two distinct ways: by binding to its promoter and, at the same time, by indirect activation through OsWRKY47. In the second transcriptional regulatory cascade, OsWRKY47 acted downstream of OsWRKY10, and OsWRKY88 acted upstream. These OsWRKY10 transcriptional regulatory cascades played important roles in basal defense and Xa1-mediated resistance to enable the mounting of a rapid immune response against pathogens.