Design and preparation of pH-sensitive cytotoxic liposomal formulations containing antitumor colchicine analogues for target release.

Herein, we describe the synthesis of pH-sensitive lipophilic colchicine prodrugs for liposomal bilayer inclusion, as well as preparation and characterization of presumably stealth PEGylated liposomes with above-mentioned prodrugs. These formulations liberate strongly cytotoxic colchicinoid derivatives selectively under slightly acidic tumor-associated conditions, ensuring tumor-targeted delivery of the compounds. The design of the prodrugs is addressed to pH-triggered release of active compounds in the slight acidic media, that corresponds to tumor microenvironment, while keeping sufficient stability of the whole formulation at physiological pH.

Proprioceptive Modulation of Pallidal Physiology in Cervical Dystonia.

Background: There is a growing body of evidence suggesting that botulinum toxin can alter proprioceptive feedback and modulate the muscle-spindle output for the treatment of dystonia. However, the mechanism for this modulation remains unclear.

Methods: We conducted a study involving 17 patients with cervical dystonia (CD), seven of whom had prominent CD and 10 with generalized dystonia (GD) along with CD.

DYT1 dystonia: Neurophysiological properties of the pallidal activity.

Objectives: The aim of this paper is to find the differences in the physiology of the pallidal neurons in DYT1 and non-DYT1 dystonia.

Methods: We performed microelectrode recording of the single unit activity in both segments of the globus pallidus during stereotactic implantation of electrodes for deep brain stimulation (DBS).

Results: We found a reduced firing rate, reduced burst rate, and increased pause index in both pallidal segments in DYT1.

Assessment of Safety and Prophylactic Efficacy of the EpiVacCorona Peptide Vaccine for COVID-19 Prevention (Phase III).

The State Research Center of Virology and Biotechnology "VECTOR" of the Federal Service for the Oversight of Consumer Protection and Welfare (Rospotrebnadzor) has developed the peptide-based EpiVacCorona vaccine, which is the first synthetic peptide-based antiviral vaccine for mass immunization in international vaccinology. An early clinical trial (Phase I-II) demonstrated that the EpiVacCorona vaccine is a safe product. The "Multicenter double-blind, placebo-controlled, comparative, randomized trial to assess the tolerability, safety, immunogenicity and prophylactic efficacy of the EpiVacCorona COVID-19 vaccine based on peptide antigens in 3000 volunteers aged 18 years and older" was performed regarding vaccine safety.

Effects of neck proprioceptive modulation on pallidal network connectivity in dystonia.

Cervical dystonia (CD) is the third most common movement disorder affecting 1 million people worldwide. Proprioceptive modulation is the hallmark of contemporary therapies for dystonia, but the mechanism for this intervention is unclear. We studied proprioceptive influence on CD by measuring the spontaneous single-neuron responses and local field potentials (LFP) from the globus pallidus interna (GPi) in 17 CD patients (9 isolated CD and 8 with CD as a feature of generalized dystonia).