Distal Radiation Access as an Alternative to Conventional Radial Access for Coronary Angiography and Percutaneous Coronary Interventions (According to TENDERA Trial).

The aim of this study was to assess the immediate and medium-term (3 months) results of the safety and efficacy of distal radial access (DRA) in coronary interventions compared with conventional transradial radial access (TRA). TRA is the recommended access for coronary procedures because of increased safety: fewer local complications, large and small bleeding. Recently, DRA has emerged as a promising alternative access to minimize radial artery occlusion (RAO) risk, as well as other complications. A large-scale, international, randomized trial comparing medium-term results with TRA and DRA is lacking. An analysis of 776 patients of the prospective randomized TENDERA trial was carried out: the distal artery access group (DRA) - 391, the transradial access group (TRA) - 385. Statistically more often the crossover access was in the DRA group (5.1% and 0.8%, P < 0.001). The primary endpoint was early or late thrombosis/occlusion of the radial artery (RA). Secondary endpoints: (1) composite complications from access vessels; (2) access parameters. Statistically significant differences were obtained for the primary endpoint: DRA 2.7% (n = 10), TRA 6.8% (n = 26), P = 0.008. Occlusion of the distal radial artery (DRAt), with patent RA: DRA 1.3% (n = 5), TRA 0 (0), P = 0.023. At the secondary composite endpoint, statistically significant differences were obtained for the following groups of complications: BARC type I bleeding (DRA: 3.8% (n = 14), TRA: 21.7% (n = 83), P < 0.001); hematoma larger than 5 cm on day 1 (DRA: 10% [n = 37], TRA: 25.9% [n = 98], P < 0.001); hematoma larger than 5 cm on day 7 (DRA: 12.4% [n = 45], TRA: 34.6% [n = 132], P < 0.001). Of the access parameters, the following statistically significantly differed: puncture time DRA 19.0 (8.0; 50), TRA 13.5 (5.0; 29), P < 0.001; insertion of introducer DRA 42.0 (26.0; 84.0), TRA 35.0 (23.0; 55.0), P < 0.001, access artery hemostasis duration (min.) DRA 180.0 (120.0; 480.0), TRA 155.0 (115.0; 195.0), P < 0.001. The duration of the procedure and fluoroscopy, radiation dose, RA spasm in both groups had no statistically significant differences. In the TENDERA trail, DRA demonstrated efficacy and safety in interventional coronary interventions compared with TRA in the medium-term follow-up period: a statistically significant lower incidence of RA occlusion and local complications.

Spin Fine Structure Reveals Biexciton Geometry in an Organic Semiconductor.

In organic semiconductors, biexcitons are key intermediates in carrier multiplication and exciton annihilation. Their local geometry governs their electronic properties and yet has been challenging to determine. Here, we access the structure of the recently discovered S=2 quintet biexciton state in an organic semiconductor using broadband optically detected magnetic resonance. We correlate the experimentally extracted spin structure with the molecular crystal geometry to identify the specific molecular pairings on which biexciton states reside.

[IMMUNOLOGICAL AND NON-IMMUNOLOGICAL PATHOGENETIC MECHANISMS OF DEVELOPMENT OF COMPLICATED FORMS OF ATOPIC DERMATITIS (REVIEW)].

Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Causes of severe AD are individual in each patient (e.g. genetic, barrier function, allergies). In this review, we will examine the highly complex interplay among skin barrier abnormality, allergy, immune dysregulation and antimicrobial peptide as a trinity in the development of AD. Studying of pathogenesis of formation of the complicated current the AD is a key problem of successful control as contamination of skin, and allergic inflammation.

Postsynaptic protein phosphorylation and LTP.

Prolonged changes in synaptic strength, such as those that occur in LTP and LTD, are thought to contribute to learning and memory processes. These complex phenomena occur in diverse brain structures and use multiple, temporally staged and spatially resolved mechanisms, such as changes in neurotransmitter release, modulation of transmitter receptors, alterations in synaptic structure, and regulation of gene expression and protein synthesis. In the CA1 region of the hippocampus, the combined activation of SRC family tyrosine kinases, protein kinase A, protein kinase C and, in particular, Ca2+/calmodulin-dependent protein kinase II results in phosphorylation of glutamate-receptor-gated ion channels and the enhancement of subsequent postsynaptic current. Crosstalk between these complex biochemical pathways can account for most characteristics of early-phase LTP in this region.

Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors.

The ability of central glutamatergic synapses to change their strength in response to the intensity of synaptic input, which occurs, for example, in long-term potentiation (LTP), is thought to provide a cellular basis for memory formation and learning. LTP in the CA1 field of the hippocampus requires activation of Ca2+/calmodulin-kinase II (CaM-KII), which phosphorylates Ser-831 in the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor (AMPA-R), and this activation/phosphorylation is thought to be a postsynaptic mechanism in LTP. In this study, we have identified a molecular mechanism by which CaM-KII potentiates AMPA-Rs. Coexpression in HEK-293 cells of activated CaM-KII with GluR1 did not affect the glutamate affinity of the receptor, the kinetics of desensitization and recovery, channel rectification, open probability, or gating. Single-channel recordings identified multiple conductance states for GluR1, and coexpression with CaM-KII or a mutation of Ser-831 to Asp increased the contribution of the higher conductance states. These results indicate that CaM-KII can mediate plasticity at glutamatergic synapses by increasing single-channel conductance of existing functional AMPA-Rs or by recruiting new high-conductance-state AMPA-Rs.

[The effect of radiation factors on cerebrovascular diseases in the region of northern Bukovina]. / Vplyv radiatsiïnykh chynnykiv na tserebrovaskuliarni zakhvoriuvannia v rehioni Pivnichnoï Bukovyny.

Correlation was studied between indices for prevalence and incidence of cerebrovascular diseases (CVD) and level of radioactive contamination in the region of northern Bukovina. As far as CVD formation, prevalence, and incidence rate is concerned, long-term exposure to small doses of ionizing radiation (cesium and strontium) makes for augmentation or lowering of CVD levels depending on their form, age, and place of residence of those having become victims of the Chernobyl accident.

Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation.

Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.

Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor.

Ca2+/CaM-dependent protein kinase II (CaM-KII) can phosphorylate and potentiate responses of alpha-amino3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptors in a number of systems, and recent studies implicate this mechanism in long term potentiation, a cellular model of learning and memory. In this study we have identified this CaM-KII regulatory site using deletion and site-specific mutants of glutamate receptor 1 (GluR1). Only mutations affecting Ser831 altered the 32P peptide maps of GluR1 from HEK-293 cells co-expressing an activated CaM-KII. Likewise, when CaM-KII was infused into cells expressing GluR1, the Ser831 to Ala mutant failed to show potentiation of the GluR1 current. The Ser831 site is specific to GluR1, and CaM-KII did not phosphorylate or potentiate current in cells expressing GluR2, emphasizing the importance of the GluR1 subunit in this regulatory mechanism. Because Ser831 has previously been identified as a protein kinase C phosphorylation site (Roche, K. W., O'Brien, R. J., Mammen, A. L., Bernhardt, J., and Huganir, R. L. (1996) Neuron 16, 1179-1188), this raises the possibility of synergistic interactions between CaM-KII and protein kinase C in regulating synaptic plasticity.

Identification of a Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in non-N-methyl-D-aspartate glutamate receptors.

Glutamate receptor ion channels are colocalized in postsynaptic densities with Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II), which can phosphorylate and strongly enhance non-N-methyl-D-aspartate (NMDA) glutamate receptor current. In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. A synthetic peptide corresponding to residues 620-638 in GluR1 was phosphorylated in vitro by CaM-kinase II but not by cAMP-dependent protein kinase or protein kinase C. The 32P-labeled peptide map of this synthetic peptide appears to be the same as the two-dimensional peptide map of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors phosphorylated in cultured hippocampal neurons by CaM-kinase II described elsewhere. This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.

Mechanism of long-lasting block of ganglion nicotinic receptors by mono-ammonium compounds with long aliphatic chain.

The effect of long-chain mono-ammonium compounds (long-chain MACs), t-butyldecylammonium (IEM-1078), 2,2,6,6-tetramethyldecylpiperidine (IEM-1559), and diisopropyldecylammonium (IEM-1194), on nicotinic acetylcholine receptors (nAChRs) was studied in sympathetic ganglion neurons using the patch clamp method. Long-chain MACs (1-10 microM) strongly inhibited acetylcholine (ACh)-induced current (ACh-current); the block persisted for hours after washing the drugs out. Short-chain MACs had a much weaker and completely reversible blocking effect. Suppression of ACh-current by MACs was dose- and voltage-dependent; it was absent at low ACh doses or at potentials > or = 60 mV and increased with higher ACh doses or hyperpolarization. The second of two ACh-currents induced by paired application of ACh was inhibited by long-chain MACs more strongly than the first. This use-dependent block also persisted for hours after washing the drugs out. Additional inhibition of the second ACh-current was reduced by lengthening the time interval between ACh applications in the pair. Time constants of the recovery of the second ACh-current in the presence and after washing out of long-chain MACs were similar, ranging from 45 to 140 s at -50 mV for different long-chain MACs, and decreased with de- or hyperpolarization. The use-dependent block produced by long-chain MACs could be prevented by another long-chain MAC with a small ammonium head (IEM-1195, 75-100 microM) or trimethaphan (30 microM), a competitive antagonist of ACh in ganglia. Neither the short-chain MAC (IEM-1405, 100 microM) nor ACh (100 microM) could exert this protective effect. Long-chain MACs did not exert any use-, dose- or voltage-dependent suppression of ACh-current when applied intracellularly. Single-channel conductance was not affected by IEM-1194 (3-10 microM). We suggest that inhibition of ACh-current by long-chain MACs is accounted for by (i) a long-lasting, apparently irreversible, binding of the drug near the channel of nAChR via its long aliphatic chain and (ii) a slow reversible block of the nAChR channel with the MAC's ammonium head.

ATP mediates fast synaptic transmission in mammalian neurons.

In addition to its diverse functions inside cells, ATP can act at several types of cell-surface receptor. One of these (P2X-purinoceptor) is believed to be a ligand-gated cation channel. The presence of P2X receptors on autonomic, sensory and central neurons suggests that ATP might be released to act as a fast excitatory synaptic transmitter. Here we record excitatory synaptic potentials and currents from cultured coeliac ganglion neurons which are mimicked by ATP, blocked by the P2-purinoceptor antagonist suramin, desensitized by alpha,beta-methylene-ATP and unaffected by antagonists acting at nicotine, 5-hydroxytryptamine, N-methyl-D-aspartate (NMDA), non-NMDA glutamate, gamma-aminobutyric acid (GABA), noradrenaline or adenosine receptors. We conclude that ATP is the neurotransmitter at this neuroneuronal synapse.

[Embolization of the hepatic artery in the treatment of malignant tumors of the liver]. / Embolizatsiia pechenochnoi arterii v lechenii zlokachestvennykh opukholei pecheni.

The results of therapeutic hepatic artery embolization (HAE) in 25 patients with malignant unresectable tumors of the liver are discussed. The proximal segments of the hepatic artery were occluded by metal spirals. Thrombosis of the portal vein was accepted as an absolute contraindication for HAE, and a tumor involving more than 50% of the volume of the liver and chronic hepatic insufficiency were considered relative contraindications. After the intervention signs of subjective improvement were noted in 73.9% and signs of objective improvement in 65.2% of cases. The mortality after HAE was 4.2%. The obtained results are evidence of the efficacy of proximal HAE as a method for the treatment of inoperable malignant tumors of the liver.

Role of disulphide bonds in burst-like activity of nicotinic acetylcholine receptor channels in rat sympathetic neurones.

1. The effects of reduction of disulphide bonds in nicotinic acetylcholine receptors (nicotinic AChRs) with dithiothreitol (DTT) were studied in rat superior cervical ganglion neurones using the patch-clamp method in whole-cell and cell-attached recording modes. 2. Dithiothreitol (1 mM) markedly reduced the ACh-induced membrane current, while the action of ACh remained reversible. Conversely, bromoacetylcholine (BrACh), if applied after the treatment with DTT, caused irreversible activation of nicotinic AChRs manifested in the appearance of a non-declined steady-state component in BrACh-induced currents accompanied by increased membrane current fluctuations. The successive reoxidation of sulphydryl groups by potassium ferricyanide (1 mM-ferricyanide) restored the response to ACh. Ferricyanide itself had a weaker inhibitory effect on the ACh-induced current, compared to the effect of DTT. 3. As a result of the action of DTT (1 mM), the spectrum of BrACh-induced current noise shifted to a higher frequency range. 4. The distributions of durations of the gaps (closed states) and the bursts (the states identified as open states after the shortest gaps were ignored) in single-channel activity of native (non-treated with DTT) nicotinic AChRs caused by ACh (30 microM) and BrACh (30 microM) were similar and both revealed four to five and two to three components for gap intervals and burst durations respectively. 5. Single-channel behaviour of reduced nicotinic AChRs was similar for both ACh and BrACh as agonists, but significantly differed from that in the native one. The first difference was the marked increase in the frequency of the appearance of long closed states of the channel that was presumably due to enhanced receptor desensitization. The second difference was an almost complete disappearance of long bursts associated with disappearance of the fastest component in gap interval distribution. 6. Mean conductance of single nicotinic AChR channels decreased by approximately 20% in the reduced receptor compared with that in the native one, for both agonists. 7. The results suggest a critical role of disulphide bonds for the functioning of native neuronal nicotinic AChRs: the disruption of disulphide bonds leads to the loss of burst-like kinetics of the nicotinic AChR ionic channel.

[Methods of creating a lymphovenous anastomosis in the neck in the treatment of lymphostasis in liver cirrhosis]. / Sposoby formirovaniia limfovenoznogo anastomoza na shee po povodu limfostaza pri tsirroze pecheni.

Certain technical moments of forming lymphovenous anastomoses in patients with cirrhosis of the liver are described. An experience with 97 operations has shown that the technical means proposed allow postoperative complications to be avoided.

5-HT3 receptors are membrane ion channels.

The neurohormone 5-hydroxytryptamine (5HT or serotonin) exerts its effects by binding to several distinct receptors. One of these is the M-receptor of Gaddum and Picarelli, now called the 5-HT3 receptor, through which 5-HT acts to excite enteric neurons. Ligand-binding and functional studies have shown that the 5-HT3 receptor is widely distributed in peripheral and central nervous tissue and evidence suggests that the receptor might incorporate an ion channel permeable to cations. We now report the first recordings of currents through single ion channels activated by 5-HT3 receptors, in excised (outside-out) membrane patches from neurons of the guinea pig submucous plexus. Whereas application of acetylcholine activated predominantly a 40-pS channel, 5-HT caused unitary currents apparently through two channels of conductances of 15 and 9 pS, which were reversibly blocked by antagonists of the 5-HT3 receptor. Receptors for amine neurotransmitters, including 5-HT1 and 5-HT2, have previously been thought to transduce their effects through GTP-binding proteins: the direct demonstration that 5-HT3 receptors are ligand-gated ion channels implies a role for 5-HT, and perhaps other amines, as a 'fast' synaptic transmitter.

[The "trap"--a modification of the block of neuronal nicotinic cholinoceptors]. / "Lovushka"--raznovidnost' bloka neironnykh nikotinovykh kholinoretseptorov.

The effect of IEM-1742, a pentaethonium derivative, on the currents induced by iontophoretic applications of acetylcholine was studied in rat superior cervical ganglion neurons using patch-clamp method in the whole-cell modification. Blocking action increased with membrane hyperpolarization and was removed by strong membrane depolarization. Apparent dissociation constant for the receptor-blocker reaction was found to be (2.9 +/- 0.6) 10(-6) M (n = 6) at -50 mV and 20-23 degrees C. IEM-1742 blocks the nicotinic acetylcholine receptor in its activated form. The dissociation of IEM-1742 from the receptor was drastically accelerated during its activation by agonist (trap-block). Trapped receptor was not released from the blocker only by membrane depolarization to the level at which any blocking effect is absent. The data obtained show that IEM-1742 in rat sympathetic ganglion neurons acts in the potential-dependent manner and displays a trap-effect.

[Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats]. / Mekhanizm deistviia tubokurarina na nikotinovye kholinoretseptory neironov simpaticheskogo gangliia krysy.

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.

[The potential dependence of acetylcholine-activated membrane conductance in sympathetic ganglion neurons]. / Potentsialozavisimost' aktiviruemoi atsetilkholinom provodimosti membran v neironakh simpaticheskogo gangliia.

Membrane conductance activated by acetylcholine (ACh-conductance) was studied in rat isolated superior cervical ganglion neurons by means of the patch-clamp method in the whole-cell recording mode. It was found that ACh-conductance was increased or decreased with membrane hyper- or depolarization, respectively. The decrease in ACh-conductance was not associated with the reversal of ACh-current or with the presence of Ca2+ ions in external solution. The time constant of voltage-jump relaxation of ACh-current revealed e-fold increase with membrane hyperpolarization by 70 mV, which corresponded to the voltage dependence of ACh-conductance. Basing upon these results it was concluded that the voltage dependence of ACh-conductance is mostly determined by the voltage dependence of nicotinic receptor channel gating kinetics.

Single channels activated by acetylcholine in rat superior cervical ganglion.

1. The elementary currents flowing through single channels opened by acetylcholine were recorded in rat superior cervical ganglion neurones using patch-clamp methods. Acetylcholine (30 microM) was included in the patch electrode (cell-attached recordings) or applied by ionophoresis (outside-out configuration). All measurements were made at 23-25 degrees C and mostly at -110 mV. 2. Channel openings appeared both as single events and as bursts of events. One population of the currents observed had a conductance of 20.0 +/- 0.2 pS (mean +/- S.E. of mean, n = 4). A second population had a conductance of about 50 pS, occurred more rarely, and was not included in further analysis. 3. Four channel closed time periods and two channel open time periods were found from the distributions of closed and open times. It was found that shorter channel openings (about 0.2 ms) appeared in isolation, whereas longer openings (duration 1.3 +/- 0.2 ms, n = 4) appeared as bursts of openings separated by the shortest channel closed time periods (about 0.15 ms). The next shortest closed time (about 2 ms) apparently corresponds to the lifetime of the channel not activated by acetylcholine. The two longer closed times (about 80 ms and 1 s) may reflect desensitization. The mean burst duration was 8.5 +/- 1.2 ms (n = 4), giving about six openings per burst. 4. Because the time constant of decay of the excitatory post-synaptic current is more similar to the burst duration than to the duration of individual single openings, it is suggested that acetylcholine released from presynaptic nerves may result in a burst of openings rather than a single opening. 5. On the basis of the above assumption, the rate constants were calculated for a sequential model in which acetylcholine binds to the receptor (forward rate k + 1 = 2.3 X 10(7) M-1 s-1; reverse rate k-1 = 1235 s-1) which then undergoes a conformational change to an open state (forward rate beta = 6293 s-1; reverse rate alpha = 894 s-1). 6. When heptamethonium (30 microM) was added to the solution in the patch electrode, the burst duration was markedly shortened, but there was no change in the closed time between two openings within the burst. This effect was voltage-dependent, which suggests that heptamethonium binds to the channel after it is opened by acetylcholine.