Acetohydroxamic acid salts: mild, simple and effective degradation reagents to counter Novichok nerve agents.

Novichoks is the latest known class of organophosphorus nerve agents to be developed. These highly lethal persistent agents, which exert their toxicity mainly through dermal exposure, pose new major challenges in mitigating their effect, mainly in respect to decontamination and medical countermeasures. Herein we report on the effective degradation of Novichok agents (A-230, A-232 and A-234) by hydroxamic acid salts.

"Catch-up" therapy: combining antidotal treatment with dermal application of AHA following percutaneous VX poisoning in the domestic swine.

Low-volatility organophosphorus chemical warfare agents (OP CWAs) are cholinesterase inhibitors which easily absorb into the skin, leading to the formation of a dermal depot from which they slowly enter the bloodstream. This leads to sustained cholinergic hyperstimulation, which if untreated may lead to death. However, current available countermeasures are not adequate to neutralize the agent residing in the dermal depot.

Gene Therapy for Regenerative Medicine.

The development of biological methods over the past decade has stimulated great interest in the possibility to regenerate human tissues. Advances in stem cell research, gene therapy, and tissue engineering have accelerated the technology in tissue and organ regeneration. However, despite significant progress in this area, there are still several technical issues that must be addressed, especially in the clinical use of gene therapy.

Solid lipid microspheres decorated nanoparticles as drug carriers.

While Pickering emulsions have been known since 1906, where oil droplets are dispersed in aqueous media owing to nanoparticles decorating each oil droplet, no solid lipid microparticles decorated with nanoparticles have been described. These Solid-Pickering microparticles are surfactant-free micro-scale spherical active agent carriers composed of beeswax as a natural solid lipid with chitosan and starch nanoparticles embedded in the surface. Microparticles of this type were made by dispersing molten lipid in hot aqueous media containing dispersed nanoparticles to create microdroplets.

Safety Evaluation of Nanotechnology Products.

Nanomaterials are now being used in a wide variety of biomedical applications. Medical and health-related issues, however, have raised major concerns, in view of the potential risks of these materials against tissue, cells, and/or organs and these are still poorly understood. These particles are able to interact with the body in countless ways, and they can cause unexpected and hazardous toxicities, especially at cellular levels.

Towards catch-up therapy: evaluation of nucleophilic active pharmaceutical ingredients for the treatment of percutaneous VX poisoning, in-vial and in-vitro studies.

Dermal exposure to low volatility organophosphorus chemical warfare agents (OP CWA) poses a great risk to the exposed person. Due to their lipophilic nature, these compounds rapidly absorb into the skin, leading to the formation of a "dermal reservoir" from which they slowly enter the bloodstream causing prolonged intoxication. Traditionally, strategies to counter the toxicity of such substances consist of chemical decontamination/physical removal of the residual agent from the skin surface (preferably as soon as possible following the exposure) and administration of antidotes in the case of intoxication signs.

Active and Strippable PVA/Borax/NaBO Hydrogel for Effective Containment and Decontamination of Chemical Warfare Agents.

Active gels present unique potential for the decontamination of chemical warfare agents (CWAs) as they strongly adhere to surfaces, thus allowing prolonged decontamination time. Herein, we present a decontamination hydrogel based on polyvinyl alcohol/borax, which contains sodium perborate (NaBO), as an in situ source of the active ingredient hydrogen peroxide. Developed as a binary formulation, this gel instantly forms and effectively sticks when sprayed on various matrices, including porous and vertically positioned matrices.

Recent Developments in Solid Lipid Microparticles for Food Ingredients Delivery.

Health food has become a prominent force in the market place, influencing many food industries to focus on numerous bioactive compounds to reap benefits from its properties. Use of these compounds in food matrices has several limitations. Most of the food bio-additives are sensitive compounds that may quickly decompose in both food and within the gastrointestinal tract.

Lessons Learned from a Systems Approach to Engaging Patients and Families in Patient Safety Transformation.

Background: Effective patient- and family-centered care requires a dedication to engaging patients and family members in health system redesign to improve the quality, safety, and experience of care. Provided here are lessons learned six years after establishing an infrastructure of patient and family advisory councils (PFACs) focused on improving health care quality and safety.

Context: A large regional health care system with multiple hospitals and ambulatory care delivery sites in the eastern United States adopted a systemwide approach to Patient and Family Advisory Councils on Quality and Safety (PFACQS) in 2012.

AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.

We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers.

Diadenosine and diuridine poly(borano)phosphate analogues: synthesis, chemical and enzymatic stability, and activity at P2Y1 and P2Y2 receptors.

Dinucleoside polyphosphates, NpnN', exert their physiological effects via P2 receptors. They are attractive drug targets as they offer better stability and specificity compared to nucleotides, the most common P2-receptor ligands. To further improve the properties of NpnN', which are still pharmacologically unsatisfactory, we developed novel boranophosphate isosteres of dinucleoside polyphosphates, denoted as Npn(B)N.

Molecular recognition in purinergic receptors. 2. Diastereoselectivity of the h-P2Y1-receptor.

In the companion paper, part 1, we described the construction of an improved molecular model for the h-P2Y1 receptor (h-P2Y1-R) and proposed a rational for the stereoelectronic selectivity of the receptor. Here, we extend our studies on the molecular recognition of the h-P2Y1-R to the exploration of the diastereoselectivity of this receptor. For this purpose, we implemented an integrative approach combining synthesis, spectral analysis, biochemical assays, and computational analysis.

Adenosine 5'-O-(1-boranotriphosphate) derivatives as novel P2Y(1) receptor agonists.

P2-receptors (P2-Rs) represent important targets for novel drug development. Most ATP analogues proposed as potential drug candidates have shortcomings such as limited receptor-selectivity and limited stability that justify the search for new P2-R agonists. Therefore, a novel series of nucleotides based on the adenosine 5'-O-(1-boranotriphosphate) (ATP-alpha-B) scaffold was developed and tested as P2Y(1)-R agonists.