Parameters of cutaneous microvasculature in men of working age with newly diagnosed arterial hypertension.

OBJECTIVE: To investigate structural and functional features of cutaneous microvasculature in men of working age with newly diagnosed arterial hypertension (AH). MATERIALS AND METHODS: The study included 161 apparently healthy men from 30 to 60 years, who underwent a comprehensive examination of cardiovascular system "from the heart to the capillaries". Control group (CG) included 60 normotensive men. AH group included 101 men with elevated BP. RESULTS: There is no rarefaction of the capillary bed and latent fluid retention in the interstitial space in the skin in men with AH. No data were obtained for increased endothelial, neurogenic and myogenic tone of resistive cutaneous precapillary arterioles in AH group, but a decrease in the perfusion efficiency of the endothelial and myogenic mechanisms of tissue perfusion modulation was noted. CONCLUSION: Obtained results allow making the assumption that metabolic disorders at the level of capillaries that are of a systemic nature prevail in men with the onset of AH.

[Analysis of changes in central macular thickness based on optical coherence tomography angiography findings in retinal vein occlusion]. / Izmeneniya tsentral'noi zony glaznogo dna pri retinal'nykh venoznykh okklyuziyakh po dannym opticheskoi kogerentnoi tomografii-angiografii.

AIM: To investigate the relationship between OCT angiography measurements and central fundus changes in patients with retinal vein occlusion (RVO). MATERIAL AND METHODS: The study enrolled 21 RVO patients aged from 55 to 86 years (69.9±2.28 years), including 8 patients with ischemic central RVO (I-CRVO; 73.6±3.4 years on average) and 13 patients with branch RVO (BRVO; 67.6±3.0 years on average). Of the latter, 8 cases were ischemic (I-BRVO) and 5 non-ischemic (NI-BRVO). OCT angiography (OCTA) was performed using RTVue XR Avanti (Optovue, USA) tomograph in the Angio Retina mode. RESULTS: A direct correlation was found between visual acuity and the degree of macular perfusion when assessing a scanning area of 6x6 mm. Having compared the degree of perfusion in groups, we have revealed that it changed significantly regardless of the size of the area scanned and the radius of the region of interest. Patients with ischemic CRVO demonstrated the lowest perfusion (Flow Area). As to ischemic and non-ischemic BRVO patients, the difference between them was only noticed with small scanning area (3x3 mm). Another statistically significant difference was shown for the blood flow index in the I-CRVO and NI-BRVO groups with scan area of 3x3 mm. Of 8 I-CRVO patients, 4 demonstrated areas of hypoperfusion within both superficial and deep vascular plexuses, while the other 4 - within the deep plexus only. In the I-BRVO group, 7 patients had hypoperfusion within both superficial and deep vascular plexuses and just 1 - within the deep plexus. In the NI-BRVO group all 5 patients had hypoperfusion of deep layers with no involvement of the superficial plexus. CONCLUSION: The value of information on vascular perfusion in all layers of the central retina provided by OCT angiography is very high, which makes it useful for the detection of microvascular abnormalities in patients with retinal vein occlusions.

Imaging of cationic multifunctional liposome-mediated delivery of COX-2 siRNA.

Liposomes are a useful means of delivering molecular targeting agents such as small interfering RNA (siRNA) to downregulate specific pathways important in cancer growth and progression. The ability to non-invasively image these carriers is important to ascertain their delivery within the tumor. As cyclooxygenase-2 (COX-2) is an important therapeutic target in cancer, we investigated loading COX-2-specific siRNA into cationic liposomes containing MR contrast agents for imaging delivery in cancer cells and tumors. COX-2 and GAPDH siRNA, as well as Magnevist or Feridex, were loaded directly into the liposomes. These lipoplexes were used for cell transfection of the poorly differentiated and highly metastatic breast cancer cell line MDA-MB-231. PEGylated liposomes loaded with Feridex and fluorescently labeled COX-2 siRNA were used for in vivo delivery of lipoplexes in MDA-MB-231 breast cancer xenografts in female SCID mice. Transient transfection assays demonstrated potent and specific downregulation of the COX-2 protein in cells in culture. Tail vein injections of PEGylated COX-2 lipoplexes resulted in intratumoral delivery of siRNA. Biodistribution studies showed significant localization in the lung, liver and kidney at 24 h. These data demonstrate the feasibility of liposomal-mediated delivery of COX-2-specific siRNA to downregulate COX-2 in cancer cells, and multi-modality imaging of the delivery of specific siRNA in tumors.

Cubic versus spherical magnetic nanoparticles: the role of surface anisotropy.

The magnetic properties of maghemite (gamma-Fe2O3) cubic and spherical nanoparticles of similar sizes have been experimentally and theoretically studied. The blocking temperature, T(B), of the nanoparticles depends on their shape, with the spherical ones exhibiting larger T(B). Other low temperature properties such as saturation magnetization, coercivity, loop shift or spin canting are rather similar. The experimental effective anisotropy and the Monte Carlo simulations indicate that the different random surface anisotropy of the two morphologies combined with the low magnetocrystalline anisotropy of gamma-Fe2O3 is the origin of these effects.

A comparison of the synaptic proteome in human chronic schizophrenia and rat ketamine psychosis suggest that prohibitin is involved in the synaptic pathology of schizophrenia.

Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a hypofunction of N-methyl-D-aspartate receptor-mediated signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse. We have employed two-dimensional gel electrophoresis in conjunction with mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine. We found consistent changes in the synaptic proteomes of human schizophrenics and in rats with induced ketamine psychosis compared to controls. However, commonly regulated proteins between both groups were very limited and only prohibitin was found upregulated in both chronic schizophrenia and the rat ketamine model. Prohibitin, however, could be a new potential marker for the synaptic pathology of schizophrenia and might be causally involved in the disease process.

The effects of ladasten on dopaminergic neurotransmission and hippocampal synaptic plasticity in rats.

Derivatives of adamantane, like memantine, are potentially neuroprotective drugs for the favourable care of Alzheimer's and Parkinson's diseases. A further adamantane derivate is N-(2-adamantyl)-N-(para-bromophenyl)-amine (ladasten) which is capable to modulate animal performance in different learning paradigms. To clarify if some of those behavioural alterations are mediated by modulation of catecholamine syntheses we studied the effects of single administration of ladasten (50 mg/kg, per os) on catecholamines' biosynthesis in the ventral tegmental area, nucleus accumbens, hypothalamus, striatum and hippocampus. We found that ladasten differentially regulates tyrosine hydroxylase mRNA and protein as well as dopamine and L-DOPA content. We then investigated the effects of ladasten on activity-dependent hippocampal synaptic plasticity in vitro and found that application of 10 microM ladasten transforms short-term potentiation of synaptic transmission to a long-lasting form. A transformation of short-term into long-term potentiation was also observed, when ladasten was applied 40 min after a single 100 Hz 200 ms tetanization. This reinforcement was blocked by the protein synthesis inhibitor anisomycin and could be attenuated by the D1/D5 receptor antagonist SCH23390. These results suggest that ladasten induces reinforcement of short-term potentiation via protein synthesis and dopamine dependent mechanisms.

The enzymatic hydrolysis of 6-acylamino-4-methylumbelliferyl-beta-D-glucosides: identification of a novel human acid beta-glucosidase.

Fluorogenic 6-acylamino-4-methylumbelliferyl-beta-D-glucosides were found to be poor substrates for the three known human beta-glucosidases, i.e., lysosomal and non-lysosomal glucocerebrosidases and cytosolic broad-specificity beta-glucosidase. However, homogenates of human tissues and human cell types showed significant enzymatic hydrolysis of 6-ethanoylamino-4-methylumbelliferyl-beta-D-glucoside (EMGlc) due to the activity of a hitherto undescribed beta-glucosidase, called here EMGlc-ase. It was shown that the isozyme is hardly active towards 4-methylumbelliferyl-beta-D-glucoside or glucosylceramide. EMGlc-ase exhibits maximal activity at pH 4.5 and 5.0 in the absence and presence of sodium taurocholate respectively. It is a soluble lysosomal enzyme with a discrete isoelectric point of about 5.0. EMGlc-ase is not inhibited by conduritol B-epoxide, is activated by sodium taurocholate and binds strongly to Concanavalin A. This enzyme is not deficient in relation to Gaucher disease.

The use of glycosides of 6- and 8-acylamino-4-methylumbelliferone in studies of the specificity and properties of human lysosomal glycolipid hydrolases.

A series of 6- and 8-acylamino-4-methylumbelliferyl beta-D-galactopyranosides, beta-D-glucopyranosides, and alpha-L-fucopyranosides having various fatty acid residues were synthesized; 6-(9) and 8-hexadecanoylamino-4-methylumbelliferyl beta-D-galactopyranoside (10) were shown to be substrates for human galactocerebrosidase. Analogs of 9 with shorter acyl residues (octanoyl and butanoyl) were substrates for another type of beta-D-galactosidase, i.e., GM1-ganglioside-beta-D-galactosidase. The specificity of various beta-D-galactosidases for synthetic D-galactopyranosides, differing in the length and position of their acylamide residue, tested with enzyme preparations from patients with two types of glycolipidosis, Krabbe's disease (galactocerebrosidase deficiency) and GM1-beta-galactosidase deficiency), suggested that 9 is a specific substrate for galactocerebrosidase in biochemical tests for Krabbe's disease. Fluorogenic 6-octanoyl- and 6-hexadecanoyl-amino-4-methylumbelliferyl beta-D-glucopyranoside were much less readily hydrolyzed by both human and animal glucocerebrosidase than chromogenic 2-hexadecanoylamino-4-nitrophenyl beta-D-glucopyranoside. Comparison of the hydrolysis of 4-methylumbelliferyl alpha-L-fucopyranoside with that of 6-hexadecanoylamino-4-methylumbelliferyl alpha-L-fucopyranoside by multiple forms of human alpha-L-fucosidase showed that the enzyme is capable of hydrolyzing not only hydrophilic but also synthetic, lipid-like substrates.