Triplex metallohelices have enantiomer-dependent mechanisms of action in colon cancer cells.

Self-assembled enantiomers of an asymmetric di-iron metallohelix differ in their antiproliferative activities against HCT116 colon cancer cells such that the compound with Λ-helicity at the metals becomes more potent than the Δ compound with increasing exposure time. From concentration- and temperature-dependent 57Fe isotopic labelling studies of cellular accumulation we postulate that while the more potent Λ enantiomer undergoes carrier-mediated efflux, for Δ the process is principally equilibrative. Cell fractionation studies demonstrate that both enantiomers localise in a similar fashion; compound is observed mostly within the cytoskeleton and/or genomic DNA, with significant amounts also found in the nucleus and membrane, but with negligible concentration in the cytosol. Cell cycle analyses using flow cytometry reveal that the Δ enantiomer induces mild arrest in the G1 phase, while Λ causes a very large dose-dependent increase in the G2/M population at a concentration significantly below the relevant IC50. Correspondingly, G2-M checkpoint failure as a result of Λ-metallohelix binding to DNA is shown to be feasible by linear dichroism studies, which indicate, in contrast to the Δ compound, a quite specific mode of binding, probably in the major groove. Further, spindle assembly checkpoint (SAC) failure, which could also be responsible for the observed G2/M arrest, is established as a feasible mechanism for the Λ helix via drug combination (synergy) studies and the discovery of tubulin and actin inhibition. Here, while the Λ compound stabilizes F-actin and induces a distinct change in tubulin architecture of HCT116 cells, Δ promotes depolymerization and more subtle changes in microtubule and actin networks.

Polyfluorinated salicylic acid derivatives as analogs of known drugs: Synthesis, molecular docking and biological evaluation.

We have developed the convenient methods for synthesis of polyfluorosalicylic acids and their derivatives. For the first time the biological properties of polyfluorosalicylates were investigated in vitro (permeability through the biological membranes, COX-1 inhibitory action) and in vivo (anti-inflammatory, analgesic activities, acute toxicity). Molecular docking of polyfluorinated salicylates confirmed in vitro and in vivo experiments.

A feasibility study of awake videolaryngoscope-assisted intubation in patients with periglottic tumour using the channelled King Vision® videolaryngoscope.

Airway management in patients with periglottic tumour is a high-risk procedure with potentially serious consequences. There is no consensus on how best to secure the airway in this group of patients. We conducted a feasibility study of awake tracheal intubation using a King Vision® videolaryngoscope with a channelled blade in a cohort of 25 patients, with a periglottic tumour requiring diagnostic or radical surgery. We used 10% and 4% lidocaine to topicalise the airway and midazolam and remifentanil for sedation. We recorded the success rate, number of attempts, time to obtain glottic view, time to intubation and complications. Twenty-three of the 25 patients (92%, 95%CI 75-98%) were intubated with the awake videolaryngoscope-assisted technique, with 17/23 (74%, 95%CI 54-87%) intubations achieved at the first attempt. Five patients required two and one patient, three attempts at intubation. Two patients (8%, 95%CI 2-25%) could not tolerate the procedure due to inadequate topical anaesthesia. Median (IQR [range]) times to obtain glottic view and to intubate were 19 (17-22 [10-30]) s and 49 (42-71 [33-107]) s, respectively. Traces of blood in the airway were observed in 4/25 (16%, 95%CI 6-35%) patients. Although airway management in this group of patients was expected to be difficult, successful awake intubation with the King Vision videolaryngoscope was achieved in the majority of patients within less than a minute. This study highlights a number of potential advantages of awake videolaryngoscope-assisted intubation over other awake methods of securing the airway in patients with upper airway obstruction due to periglottic mass.

[Myocardial infarction in colon cancer].

Paraneoplastic syndromes have a variety of clinical manifestations most frequently resembling systemic diseases and phlebothrombosis. Also, hypercoagulative paraneoplasic syndrome may have some clinical features of myocardial infarction which makes difficult nosological diagnostics.

[Dynamics of fatty acid composition of total lipids during embryonic development of Atlantic salmon Salmo salar L].

Dynamics of fatty acid composition of total lipids was studied for freshwater salmon Salmo salar L. during its embryonic development from blastula (3 hours) up to hatching (108 days) as well as in unfertilized eggs. Stable amount of total and some saturated, monounsaturated and polyunsaturated fatty acids (PUFA) of total lipids was observed during embryonic development. Considerable changes in fatty acid composition were observed at the stage of prelarvae hatching, i.e., significant decrease of (n-6) PUFA (18:2(n-6) and 20:4(n-6)) and (n-3) PUFA and increase of total and some saturated and monounsaturated fatty acids was registered. Change in saturation ratio of membrane lipids justifies the presence of the biochemical mechanism forwarded on regulation of cell membrane enzymes in accordance with the changes of internal physiological processes taking place in the organism and fluctuations of external environmental conditions or the preparation period (as reproduction). Data on peculiarities of transformation and utilization of fatty acids during salmon embryonic development may be used for understanding of their functional role in the developing organism as well as for assessing the quality of the caviar.

[Combined low-dose antihypertensive therapy in pregnant women with hypertension and preeclampsia].

The effect of low-dose combination antihypertensive therapy in fixed form, containing 2.5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide, the clinical condition, the daily profile of blood pressure, body adrenoreactivity structural and functional parameters of the left ventricle in 28 pregnant women with preeclampsia in the background chronic hypertension (hypertension stage II, 2 nd degree) and 28 pregnant women with preeclampsia and mild to moderate severity in terms of 22-28 weeks of pregnancy. After 16 weeks of receiving a fixed form, containing 2.5 mg of bisoprolol and 6.25 mg hydrochlorothiazide, the target BP level reached 76% of pregnant women with preeclampsia with chronic hypertension and 81% - with preeclampsia. In both groups, the parameters are optimized daily profile of blood pressure, the value of the total peripheral vascular resistance.

[Docosahexaenoyl dopamine in freshwater hydra: effects on regeneration and metabolic changes].

The effects of docosahexaenoyl dopamine and docosahexaenoic acid on the regeneration of hydra gastric and basal fragments are studied. Docosahexaenoyl dopamine induced morphogenetic abnormalities such as single ectopic tentacles in the gastric region and projections in the gastric and basal regions. Docosahexaenoic acid had no effect on the morphogenesis except for a mild slowing of the regeneration rate. Since no hydrolysis of docosahexaenoyl dopamine was detected in hydra extract, it was assumed that the morphogenetic effect could be associated with the dopamine component of this complex.

[Hypertensive disease and metabolic syndrome: application of metoprolol].

The aim of this work was to study effects of metoprolol on structural and functional characteristics of left ventricle (LV), cerebral circulation (CC), microcirculation (MC), lipid spectrum, rheologic and viscous properties of blood in patients with grade II-III hypertensive disease (HD) and metabolic syndrome. 65 patients in this condition (ESH/ESC, 2007) were given metoprolol (100-150 mg/d) and indapamide (1.5 mg/d) for 6 months. Daily AP profile, structural and functional characteristics of left ventricle were evaluated before and after therapy by echocardiography, cerebral dopplerography, conjunctival biomicroscopy, measurement of MC, hemorheologic parameters, blood lipid spectrum and glucose level. The target AP level and normalization of AP daily profile were achieved in 65% of the patients. The treatment improved myocardial contractility and diastolic function, decreased LV mass, corrected autoregulation of cerebral blood flow and MC. Metoprolol was shown to be metabolically inert. The study confirmed benefits of its application to the treatment of HD with metabolic syndrome.

[N-arachidonoyl dopamine is a possible factor of the rate of tentacle formation in freshwater hydra].

The effect of N-arachidonoyl dopamine, haloperidol, and their mixture on the rate of tentacle formation was studied during regeneration of the gastral and basal fragments of freshwater hydra. Some concentrations of haloperidol inhibited the tentacle formation, which was more pronounced in the basal fragment. N-arachidonoyl dopamine accelerated the tentacle formation in both fragments, particularly, in the basal one (an inversion of the natural difference in the rate of tentacle formation between the gastral and basal fragments). After the exposure to the mixture of these drugs, the effects of each of them were observed. Mass spectrometry assay has demonstrated endogenous N-arachidonoyl dopamine in the intact hydra homogenate. The possible involvement of this acyl-neurotransmitter in the regulation of the rate of tentacle formation in regenerating hydra is discussed.

[Structural organization of neurons of spinal ganglia innervating the colon].

The localization and morphological features of viscerosensory neurons of sacral spinal ganglia (SSG), innervating the colon, were investigated. In urethane anaesthetized cats, the solution of horseradish peroxidase was injected under the serosa of ascending and descending parts of the colon as well as of the rectum. After 48 hours animals were repeatedly anesthetized and transcardially perfused. Sections of SSG were stained according to Mezulam protocol (1978). All the regions of the colon studied were shown to receive afferent innervation from neurons of SSG SI, SII and SIII. Maximum number of the labeled cells was detected in SSG SII. The intensity of afferent innervation of the colon by the neurons of SSG was found to increase along its length in cranio-caudal direction.

[Effect of aluminum and iron on lipid metabolism in aquatic invertebrates].

Methods of thin-layer, gas-liquid, and liquid chromatography were applied to the study of the effect of various concentrations of aluminum and iron salts on the contents of phospholipids, cholesterol, and fatty acids in the aquatic invertebrate Hydropsyche contubernalis L. (Trichoptera). It was found that the effect of the metals under study on lipid contents in living organisms depended on the composition of the aqueous medium and concentrations of the metals. Aluminum and iron altered the value of the cholesterol-to-phospholipid molar ratio. In the absence of lethal effects, this was indicative of attempts to switch adaptational biochemical mechanisms to stabilize cellular structures.

[Effects of arachidonoyl dopamine, haloperidol, and their mixtures on regeneration of freshwater Hydra attenuata]. / Vliianie arakhidonoildofamina, galoperidola i ikh smesei na regeneratsiiu presnovodnoi gidry Hydra attenuata.

Arachidonoyl dopamine and haloperidol, both separately and in different combinations, inhibit regeneration of the gastral and basal regions of hydra. In addition, both substances induce stable anomalies of morphogenesis in the form of outgrowths and additional tentacles in gastral regenerates. In the presence of both substances at different combinations, anomalies either do not appear altogether, or exist for a short time, thus suggesting the normalization of morphogenesis. Possible mechanisms underlying the effects of these substances are discussed.

[Effect of gamma irradiation on the preference behavior and lipid metabolism in grey garden slug Deroceras reticulatum Mull]. / Viianie gamma-oblucheniia na preferntnoe povedenie i lipidnyi obmen u sliznia setchatogo Deroceras reticulatum Mull.

We studied the preference behavior of slugs Deroceras reticulatum in experimental light, thermal, and salt gradients. The zone of each gradients preferred by the majority of individuals had the lowest contents of total lipids and total fatty acids in the tissues as compared to animals in any other zones. Hard gamma irradiation of slugs D. reticulatum proved to induce qualitative changes in salt preference, to decrease photoresponse in light gradients, and to increase lipid content in tissues.

[Effect of eprosartan on microcirculation and blood rheology in patients with hypertensive disease]. / Vliianie éprosartana na mikrotsirkuliatsiiu i reologiiu krovi u bol'nykh gipertonicheskoi bolezn'iu.

The use of eprosartan (600-1200 mg/day for 4 weeks) in 28 patients with stage II hypertensive disease was associated with improvement of parameters of microcirculation and blood rheology.

Regular structural organization of intrahemisphere interzonal connections in the visual cortex of the cat.

The aim of the present work was to conduct a morphometric analysis of the cluster organization of neurons forming interzonal corticocortical connections in the visual cortex. The investigations used a method based on retrograde transport of horseradish peroxidase and mathematical analysis of the spatial distribution of labeled cells. Measurements yielded the following quantitative characteristics of the cell distribution--the volume and linear sizes of clusters, the distance between the centers of gravity of clusters, and the periodicity in the distribution of clusters along the cortical surface. Age-related features of the distribution of cells giving rise to cortical interzonal connections were identified. The experiments showed that the pattern of the cluster organization typical of adult cats was formed by the end of the second month of life. Quantitative differences in the spatial organization of neuron groups in the cortex of visual fields 17 and 18 were demonstrated.

[Lisinopril effects on cerebral blood flow and blood rheology in hypertensive patients]. / Vliianie lizinoprila na mozgovoi krovotok i reologicheskie svoistva krovi u bol'nykh arterial'noi gipertoniei.

AIM: To access the effect of lisinopril (diroton) on cerebral circulation and blood rheology in patients with arterial hypertension stage II. MATERIAL AND METHODS: The trial included 37 patients (16 males, 21 females) with a mean arterial hypertension (AH) history 15.9 +/- 5.6 years. Diroton was given in a dose 10-40 mg/day for 6 months. Cerebral circulation (total cerebral circulation and venous outflow--TCC and VOF) was accessed by means of doppler ultrasonography. Blood and plasm rheology was determined using a rotational viscozymeter ACP-2. Instrumental tests were performed at baseline and at the end of the study. RESULTS: Rheology tests showed that diroton-treated patients achieved a significant decrease in blood viscosity in high, moderate and low shear stress and plasma viscosity, a decrease in platelet aggregation index and an increase in the index of erythrocytic deformability. All these changes were accompanied with a significant fall in fibrinogen and hematocrit. Doppler ultrasound revealed an insignificant increase in TCC and VOF. CONCLUSION: Diroton significantly improved impaired blood rheology and viscosity in AH patients as well as cerebral hemodynamics in patients with subnormal cerebral circulation and venous outflow at baseline.

[The state of hemodynamics and microcirculation in patients with hypertensive disease during long term controlled therapy with lisinopril]. / Sostoianie gemodinamiki i mikrotsirkuliatsii u bol'nykh gipertonicheskoi bolezn'iu pri dlitel'nom kontroliruemom lechenii lizinoprilom.

Lisinopril (Diroton, 10-40 mg/day) was given for 6 months to 30 patients (mean age 57.2+/-0.64 years) with stage II hypertension (WHO, 1999). Left ventricular diastolic function and microcirculation were assessed by echocardiography and biomicroscopy, respectively. Treatment with lisinopril was associated with improvements of impaired left ventricular diastolic function, structural and functional state of the heart. Parameters of microcirculatory vascular bed also improved.

[Orderly structural organization of intrahemispheric interzonal connections in the cat visual cortex]. / Uporiadochennaia strukturnaia organizatsiia vnutripolusharnykh mezhzonal'nykh sviazei v zritel'noi kore koshki.

The study was aimed at morphometric analysis of cluster organization of neurons, forming interzonal cortico-cortical connections within the visual cortex. The study employed the technique based on horseradish peroxidase retrograde transport and methods of mathematical analysis of spatial distribution of labeled cells. The quantitative characteristics of cell distribution were obtained including cluster volume and linear dimensions, distances between their centers of gravity, periodicity and distribution along cortical surface. Age-related peculiarities in the distribution of initial cells of cortical interzonal connections were found. It was demonstrated that adult cluster organization pattern was established by the end of the second postnatal month. Quantitative differences in the spatial distribution of neuronal groups in the visual cortical areas 17 and 18 were determined.