[Patogenetic therapy of patients with diabetes mellitus type 2 and cerebral vascular insufficiency].

Effectiveness of halidor preparation was assessed in a randomized open 8-weeks study in 44 patients with diabetes mellitus type 2 and chronic cerebral blood circulation disorders. A control group included 15 patients with the same pathologies who did not receive halidor. Administration of halidor in doses 100 mg 3 times daily led to the improvement of clinical state in 32 (72,7%) patients that was confirmed by statistically better performance (p<0,05) on the neuropsychological tests: MMSE by 14,7%, clock-drawing test by 16,8%, the Schult test by 23,5%.

The promise and perils of CNS drug delivery: a video debate.

Neurodegenerative and infectious disorders related to host genetics, aging, and environment are rapidly increasing. Drugs, vaccines, or regenerative proteins offer "real" possibilities for positively affecting disease outcomes but are limited by access across the blood-brain barrier. New developments in nanomedicine and cell based drug delivery are becoming available.

Novel nanomaterials for clinical neuroscience.

Neurodegenerative disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population ages. The field of nanomedicine is rapidly expanding and promises revolutionary advances to the diagnosis and treatment of devastating human diseases. This paper provides an overview of novel nanomaterials that have potential to improve diagnosis and therapy of neurodegenerative disorders.

A macrophage-nanozyme delivery system for Parkinson's disease.

Selective delivery of antioxidants to the substantia nigra pars compacta (SNpc) during Parkinson's disease (PD) can potentially attenuate oxidative stress and as such increase survival of dopaminergic neurons. To this end, we developed a bone-marrow-derived macrophage (BMM) system to deliver catalase to PD-affected brain regions in an animal model of human disease. To preclude BMM-mediated enzyme degradation, catalase was packaged into a block ionomer complex with a cationic block copolymer, polyethyleneimine-poly(ethylene glycol) (PEI-PEG).

[Helix-forming conformers in structural organization of methylamides of N-acetyl-alpha-L-amino acids. Quantum-chemical study].

Based on the results of quantum-chemical PM3 calculations, some common structural and thermodynamic properties of low-energy monopeptide conformers have been revealed that may be responsible for the initiation of alpha- or beta-like forms in polypeptide structures.

[Torsion lability of the O=C-N-H fragment in single dipeptide molecules of L-amino acids].

On the basis of ab initio MP2 and semi-empirical PM3 quantum-chemical calculations the bistability of the nonplanar O=C-N-H fragment in the structure of simple amides and dipeptides is discussed. The influence of the nature of amino acids on the structural polymorphism of the peptide group in dipeptides is shown.

Polyion complex nanomaterials from block polyelectrolyte micelles and linear polyelectrolytes of opposite charge: 1. Solution behavior.

The present study investigates whether block polyelectrolyte micelles can form soluble complexes upon interaction with oppositely charged linear polyelectrolytes. The phase behavior and molecular characteristics of the complexes were examined by turbidimetry, phase analysis, dynamic light scattering, and sedimentation velocity techniques. At an excess of polyelectrolyte micelles, soluble complexes were formed either independently on the route of preparation or, for select linear polyelectrolytes, through routes that avoided macrophase separation.

The current content of artificial radionuclides in the water of the Tobol-Irtysh river system (from the mouth of the Iset River to the confluence with the Ob River).

Data on content of (90)Sr, (137)Cs, (239,240)Pu and (3)H in water of the Tobol-Irtysh part of the Techa-Iset-Tobol-Irtysh-Ob river system (through which the "Mayak" PA radioactive wastes are transported) are presented and discussed. The data were received in 2004-2005 under the ISTC project on radioecological monitoring of the Tobol and Irtysh rivers. Monthly observations of (137)Cs, (90)Sr and (3)H content in water in the area of the Tobol and Irtysh confluence have been conducted starting from May 2004.

Block polyelectrolyte networks from poly(acrylic acid) and poly(ethylene oxide): sorption and release of cytochrome C.

A new family of block polyelectrolyte networks containing cross-linked poly(acrylic acid) (PAA) and poly(ethylene oxide) (PEO) was synthesized by copolymerization of acrylic acid and bisacrylated PEO (10 kDa). Two materials with different PEO/PAA ratios were compared with a weakly cross-linked PAA homopolymer network. The networks bound a cationic protein, cytochrome C, due to the polyion coupling, leading to the network contraction.

Nanomaterials from ionic block copolymers and single-, double-, and triple-tail surfactants.

Block ionomer complexes (BICs) are prepared from anionic block copolymers and cationic surfactants of different structure or from their mixtures. Drastic changes in the morphology and stability of BIC nanoparticles caused by changes in the composition of the surfactant mixture are demonstrated. Single-tail and double-tail surfactants appear to mix within the BIC, resulting in the formation of rather uniform BIC particles.

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders.

Neurodegenerative and infectious disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population's age. Alzheimer's disease alone currently affects 4.5 million Americans, and more than $100 billion is spent per year on medical and institutional care for affected people.

Polymer genomics: an insight into pharmacology and toxicology of nanomedicines.

Synthetic polymers and nanomaterials display selective phenotypic effects in cells and in the body signal transduction mechanisms involved in inflammation, differentiation, proliferation, and apoptosis. When physically mixed or covalently conjugated with cytotoxic agents, bacterial DNA or antigens, polymers can drastically alter specific genetically controlled responses to these agents. These effects, in part, result from cooperative interactions of polymers and nanomaterials with plasma cell membranes and trafficking of polymers and nanomaterials to intracellular organelles.

Template-assisted synthesis of nanogels from Pluronic-modified poly(acrylic acid).

A series of novel polymeric nanogels with core-shell morphology was developed. Block ionomer complexes of comb-graft poly(ethylene oxide)-b-poly(polypropylene oxide)-b-poly(ethylene oxide)-g-poly(acrylic acid) copolymers (Pluronic-PAA) and divalent metal cations were utilized as micellar templates for the synthesis of nanogels with sizes ranging from 100 to 200 nm in diameter. The Pluronic-PAA nanogels were confirmed to possess ionic cross-linked PAA cores and flexible hydrophilic shells from the Pluronic copolymer chains.

Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis.

Most potent antiretroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier.

Side chain dynamics and alternative hydrogen bonding in the mechanism of protein thermostabilization.

To elucidate the mechanism of protein thermostabilization, the thermodynamic properties of small monomeric proteins from mesophilic and thermophilic organisms have been analyzed. Molecular dynamics simulations were employed in the study of dynamic features of charged and polar side chains of amino acid residues. The basic conclusion has been made: surface charged and polar side chains with high conformational mobility can form alternative hydrogen bonded (H-bonded) donor-acceptor pairs.

Nanotools for megaproblems: probing protein misfolding diseases using nanomedicine modus operandi.

Misfolding and self-assembly of proteins in nanoaggregates of different sizes and morphologies (nanoensembles, primary nanofilaments, nanorings, filaments, protofibrils, fibrils, etc.) is a common theme unifying a number of human pathologies termed protein misfolding diseases. Recent studies highlight increasing recognition of the public health importance of protein misfolding diseases, including various neurodegenerative disorders and amyloidoses.

Block ionomer complexes as prospective nanocontainers for drug delivery.

Nanosized environmentally responsive materials are of special interest for various applications, including drug delivery. Block ionomer complexes (BIC) composed of graft-comb copolymers of Pluronic and poly(acrylic acid) (Pluronic-PAA) and a model cationic surfactant, hexadecyltrimethylammonium bromide (HTAB), were synthesized by mixing the polymer and surfactant in aqueous media. According to TEM, the resulting BIC represented spherical particles of nanoscale size (50 to 100 nm).

Polymer micelles with cross-linked ionic cores for delivery of anticancer drugs.

This work reports the design of polymer micelles with cross-linked ionic cores that display high stability. Block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) copolymer and divalent metal cations were utilized as micellar templates for the synthesis of the cross-linked micelles. Such micelles represent hydrophilic nanospheres of core-shell morphology.

Fluorescence anisotropy study of aqueous dispersions of block ionomer complexes.

Block ionomer complexes (BIC) of "dual hydrophilic" block copolymers containing ionic and nonionic blocks and oppositely charged surfactants spontaneously form colloidal particles of ca. 80 nm in diameter stable in aqueous dispersions at every composition of the mixture. Packing and dynamics of aliphatic groups of the surfactant in BIC were examined by using the quenching-resolved fluorescence anisotropy (QRFA) method with 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe.

Alteration of genomic responses to doxorubicin and prevention of MDR in breast cancer cells by a polymer excipient: pluronic P85.

Polymer therapeutics has emerged as a new clinical option for the treatment of human diseases. However, little is known about pharmacogenetic responses to drugs formulated with polymers. In this study, we demonstrate that a formulation containing the block copolymer Pluronic P85 and antineoplastic drug doxorubicin (Dox) prevents the development of multidrug resistance in the human breast carcinoma cell line, MCF7.

Pluronic Block Copolymers for Gene Delivery.

Amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide) called Pluronic or poloxamer are commercially available pharmaceutical excipients. They recently attracted considerable attention in gene delivery applications. First, they were shown to increase the transfection with adenovirus and lentivirus vectors.