The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.

Introduction: Chronic cough heavily affects patients' quality of life, and there are no effective licensed therapies available. Cough is a complication of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection, asthma, and other diseases. Patients with various diseases have a different profile of tussive responses to diverse cough triggers, thereby suggesting sundry mechanisms of neuronal dysfunctions.

Synthesis, inhibitory activity and oral dosing formulation of AV5124, the structural analogue of influenza virus endonuclease inhibitor baloxavir.

Background: The development and clinical implementation of the cap-dependent endonuclease (CEN) inhibitor baloxavir marboxil was a breakthrough in influenza therapy, but it was associated with the emergence of drug-resistant variants.

Objectives: To design and synthesize structural analogues of CEN inhibitors and evaluate their safety, pharmacokinetics and antiviral potency in vitro and in vivo.

Methods: The drug candidate AV5124 and its active metabolite AV5116 were synthesized based on pharmacophore modelling.

Higher Ca -sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity.

Aim: During early post-natal development, arterial contraction depends less on Ca -signalling pathways but more on changes in Ca -sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca -sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca -sensitivity of contraction in intact arteries of 1-week-old rats.

[Functional alterations of the arterial vessels in experimental models of type 1 diabetes mellitus].

The review analyzws the literature on the pathological alterations of endothelium, smooth muscle and vasomotor innervation of arterial vessels in animal modes of type 1 diabetes mellitus. Particular attention is paid t the analysis of mechanisms of diabetic abnormalities in the light of modern knowledge on the functioning of the main components of the vascular wall.

Trophic action of sympathetic nerves reduces arterial smooth muscle Ca(2+) sensitivity during early post-natal development in rats.

Aim: A decrease in the Ca(2+) sensitivity of smooth muscle contraction is a hallmark of functional remodelling of blood vessels during development. However, the responsible factors are largely unknown. Here, we tested the hypothesis that the post-natal decline of arterial Ca(2+) sensitivity is the result of trophic effects of sympathetic nerves.