Effect of intra-aortic balloon counterpulsation on thrombocyte ultrastructure and functional properties

Ultrastructure and function of blood platelets have been examined after intraaortic balloon counterpulsation in 9 dogs. Intraaortic balloons made of "polyurethane" (Experiment I) or "biomer" plastic (Experiment II) were used. An increase in the number of platelet microforms due to the fragmentation of the normal-sized platelets has been noted along with the ultrastructural signs of platelet activation, degranulation and alterations of plasma membrane structure. The above changes were less pronounced in experiment II.     

A model of constant color perception for continuous spectral functions

A trichromatic model is proposed of constant pattern of colour perception (MCCP) for scenes with a single illumination source. In MCCP functions of the source emission, surface reflection, photoacceptor sensitivity are approximated by the normal distribution curves. MCCP characteristics "colour tone", "cleanness", and "lightness" organize its output colour metric by the human's pattern, and in a wide range of spectral composition of illumination they are invariant under these changes. Special colorimetric regime of MCCP work which estimates the colour of visual stimulus permits a comparison between the efficiencies of two proposed algorithms of visual information processing for MCCP.     

The structural and dynamic model of the serotonin 5-HT3 receptor. Comparative analysis of the structure of the channel domain of pentameric ligand-gated ion channels

The three-dimensional structure of the 5-HT3 receptor is currently unknown. An available structure of the nicotinic acetylcholine receptor closely related by homology to the 5-HT3 receptor was used as a template for the computer-based homology modeling of the 5-HT3 receptor. The study of the ion migration through the channel by the steered molecular dynamics method has shown that the steric factor in the region of residue Thr279 and the region of Glu272, Asp293 influences the ion transmission. The characteristic of the close interaction between the ion and the amino acid substitutions of the 5-HT3 channel was studied by computing the energy profile using constraint force molecular dynamic simulations. The amino acid sequence responsible for selective ion transmission has been investigated. The structure of the channel domain of the serotonin 5-HT3 receptor as a universal functional unit of the ligand-gated ion channels was discussed.     

Serious adverse events following treatment with ivermectin for onchocerciasis control: a review of reported cases

This paper presents a summary of reported cases of Serious Adverse Events (SAEs) following treatment with Mectizan^® (ivermectin, Merck, Sharpe &; Dohme) in onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001 through a passive surveillance system. A total of 207 SAE cases were reported out of approximately 165 million reported treatments delivered during the period under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000 reported treatments. The mean age was 40 years and 70% of the cases were males. The mean time between ivermectin intake and onset of illness was 1 day. For 57% of the cases (n = 118), that was their first exposure to ivermectin. The majority of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence of SAE reporting in 1989–1991 and 1994–1995 when the program expanded to ivermectin-naïve populations. Fifty-five percent of the cases from Cameroon (i.e. 97 out of 176 cases) were encephalopathic and were reported from the central-southern region of the country; two-thirds of these cases were 'probable' or 'possible' cases of Loa loa encephalopathy temporally related to ivermectin treatment. Reporting bias may explain some but not all of the differences in SAE reporting between the 34 onchocerciasis-endemic countries that have, or have had, mass treatment programs. Further research is needed to understand the apparent clustering of encephalopathy cases in central-southern Cameroon since L. loa infection alone probably does not explain the increased incidence of this type of SAE from this region.     

Role of Membrane Microdomains in Compartmentation of cAMP Signaling

Spatially restricting cAMP production to discrete subcellular locations permits selective regulation of specific functional responses. But exactly where and how cAMP signaling is confined is not fully understood. Different receptors and adenylyl cyclase isoforms responsible for cAMP production are not uniformly distributed between lipid raft and non-lipid raft domains of the plasma membrane. We sought to determine the role that these membrane domains play in organizing cAMP responses in HEK293 cells. The freely diffusible FRET-based biosensor Epac2-camps was used to measure global cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. Disruption of lipid rafts by cholesterol depletion selectively altered cAMP responses produced by raft-associated receptors. The results indicate that receptors associated with lipid raft as well as non-lipid raft domains can contribute to global cAMP responses. In addition, basal cAMP activity was found to be significantly higher in non-raft domains. This was supported by the fact that pharmacologic inhibition of adenylyl cyclase activity reduced basal cAMP activity detected by Epac2-CAAX but not Epac2-MyrPalm or Epac2-camps. Responses detected by Epac2-CAAX were also more sensitive to direct stimulation of adenylyl cyclase activity, but less sensitive to inhibition of phosphodiesterase activity. Quantitative modeling was used to demonstrate that differences in adenylyl cyclase and phosphodiesterase activities are necessary but not sufficient to explain compartmentation of cAMP associated with different microdomains of the plasma membrane.     

Attachment of trivaline changes the specificity of binding of netropsin analogs with DNA

In the present communication, synthesis and DNA binding activities of three analogs of the antibiotic netropsin are reported. Each analog contains two N-propylpyrrolecarboxamide units linked covalently to either Dns-Gly-Val-Val-Val-Gly-Gly- (I), Val-Val-Val-Gly-Gly (II) or Gly-Gly (III). It is shown that analogs I and II can self-associate in aqueous solution and methanol as revealed from the fact that UV absorbance and circular dichroism spectra obtained for these analogs are concentration-dependent. By contrast, analogs III exists as a monomer, even at concentration levels of the order of 1.10(-3) M. Determination of the apparent sizes of intramolecular aggregates by gel-filtration shows that analog I in aqueous solution at concentration levels of the order of 1.10(-3) M forms a series of aggregates containing from 2 to 12 monomers. Analog II exhibits a lower tendency to form intermolecular aggregates as compared with that of analog I. Dimerization constants are determined for analogs I and II in aqueous solution and methanol. The binding of N-propylpyrrolecarboxamide units and peptide fragments of analog I to DNA can be independently monitored by circular dichroism and fluorescence methods. If self-associated species of analog I (or II) are present in solution, the ligand exhibits a markedly different order of base pair sequence preferencies as compared with that of analog III. The results obtained are consistent with the inference that analogs I and II in a beta-associated form recognizes base pair sequences containing two runs of 3 AT pairs separated by two GC pairs.