Myelin damage and cortical atrophy in watershed regions in patients with moyamoya angiopathy.

Background: Despite it being known that chronic ischemia results in myelin damage and gray matter atrophy, data regarding patients with moyamoya angiopathy is limited. We hypothesized that chronic ischemia in moyamoya angiopathy leads to myelin damage, especially in anterior watershed regions, as well as cortical atrophy in these areas.

Materials And Methods: Twenty adult patients with moyamoya angiopathy and 17 age- and sex-matched healthy controls were evaluated using the T1w/T2w mapping method and surface-based MR-morphometry.

[Combination treatment of cerebral arteriovenous malformations using endovascular and microsurgical techniques].

Material And Methods: The study included 40 patients with cerebral AVMs. In the study group, 14 (35%) patients underwent microsurgical resection without preliminary embolization (1st group), and 26 (65%) patients underwent combined treatment (endovascular embolization and microsurgical intervention, 2nd group). The first group included patients with S&M grade I-III AVMs, and the second group included patients with S&M grade II-V AVMs.

[The use of high-flow extracranial-intracranial artery bypass in pathology of the cerebral and brachiocephalic arteries: technical features and surgical outcomes].

Background: Poor outcomes of surgical treatment for complex cerebral aneurysms due to the development of cerebral ischemia were the cause to use cerebral revascularization surgery for this pathology.

Objective: the study objective was to master a high-flow extracranial-intracranial (EC-IC) artery bypass technique and evaluate its application in surgical treatment of complex and giant cerebral aneurysms as well as complex lesions of the brachiocephalic arteries.

Material And Methods: Fifty two patients underwent high-flow IC-EC bypass surgery; of these, 34 patients had complex cerebral aneurysms, and 18 patients had complex stenotic occlusive lesions of the brachiocephalic arteries.

[Surgical treatment of «Mirror» aneurysms of the internal carotid artery].

Background: A relatively high occurrence of "mirror" aneurysms of the anterior cerebral circulation in neurosurgical practice necessitates generalization of experience of using different surgical approaches. The choice of treatment is usually associated with the number of surgical stages.

Material And Methods: Forty nine patients (19 males and 30 females) with mirror aneurysms of the anterior circulation underwent one- and two-step surgery at the Novosibirsk Federal Center of Neurosurgery in 2013-2015.

Antiproliferative 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides, a new tubulin inhibitor chemotype.

We discovered a new chemical class of antiproliferative agents, 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides. SAR-guided optimization of the two distinct terminal fragments yielded a compound with 120 nM potency in an antiproliferative assay. Biological activity profile studies (COMPARE analysis) demonstrated that 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides act as tubulin inhibitors, and this conclusion was confirmed via biochemical assays with pure tubulin and demonstration of increased numbers of mitotic cells following treatment of a leukemia cell line.

Identification of diaryl 5-amino-1,2,4-oxadiazoles as tubulin inhibitors: the special case of 3-(2-fluorophenyl)-5-(4-methoxyphenyl)amino-1,2,4-oxadiazole.

The combination of experimental (inhibition of colchicine binding) and computational (COMPARE, docking studies) data unequivocally identified diaryl 5-amino-1,2,4-oxadiazoles as potent tubulin inhibitors. Good correlation was observed between tubulin binding and cytostatic properties for all tested compounds with the notable exception of the lead candidate, 3-(3-methoxyphenyl)-5-(4-methoxyphenyl)amino-1,2,4-oxadiazole (DCP 10500078). This compound was found to be substantially more active in our in vitro experiments than the monofluorinated title compound, 3-(2-fluorophenyl)-5-(4-methoxyphenyl)amino-1,2,4-oxadiazole (DCP 10500067/NSC 757486), which in turn demonstrated slightly better tubulin binding activity.

Trans-, cis-, and dihydro-resveratrol: a comparative study.

Background: Recent studies showed that moderate consumption of red or white wines increased the chances of breast cancer, while similar consumption of red wines, rich in trans-resveratrol (trans-R), decreased the rate of prostate cancer. This prompted us to explore the role of various forms of R in cancer proliferation.

Results: Trans-R was found to be the most potent antiproliferative agent.

Cytotoxic Activity of Peripheral Blood Mononuclear Leukocytes, Activated by Interleukin-2/β-Cyclodextrin Nanocomposition against Androgen Receptor-Negative Prostate Cancers.

Nanocomposition comprised of interleukin-2 in suboptimal noneffective concentration and β-cyclodextrin was studied in vitro. This preparation as well as interleukin-2 in optimal concentration was shown to increase natural killer activity to K-562 cells and cytotoxicity of activated peripheral blood mononuclear cells (PBMCs) against PC-3 and DU 145 cells. At the same time β-cyclodextrin or interleukin-2 in equimolar concentrations did not influence the spontaneous killer activity of PBMC.

Dihydro-resveratrol--a potent dietary polyphenol.

Dihydro-resveratrol (dihydro-R), a prominent polyphenol component of red wine, has a profound proliferative effect on hormone-sensitive tumor cell lines such as breast cancer cell line MCF7. We found a significant increase in MCF7 tumor cells growth rates in the presence of picomolar concentrations of this compound. The proliferative effect of dihydro-R was not observed in cell lines that do not express hormone receptors (MDA-MB-231, BT-474, and К-562).

Discovery and potency optimization of 2-amino-5-arylmethyl-1,3-thiazole derivatives as potential therapeutic agents for prostate cancer.

A new chemical series was identified via high-throughput screening as having antiproliferative activity on DU-145 human prostate carcinoma cell line (hit compound potency - 2.9 microM). Medicinal chemistry optimization of two peripheral diversity vectors of the hit molecule, independently, led to SAR generalizations and identification of the 'best' moieties.

Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose, and their analogs.

Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a).