Ticlopidine and clopidogrel (SR 25990C) selectively neutralize ADP inhibition of PGE1-activated platelet adenylate cyclase in rats and rabbits

Ticlopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGE1-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase. However, the drop in cAMP levels observed after addition of ADP to PGE1-stimulated control platelets was inhibited in platelets from treated animals. In contrast, the drop in cAMP levels produced by epinephrine was not prevented by either drug in rabbit platelets. In rat platelets, thrombin inhibited the PGE1-induced cAMP elevation but this effects seems to be entirely mediated by the released ADP. Under these conditions, it was not surprising to find that clopidogrel also potently inhibited that effect of thrombin on platelet adenylate cyclase. In conclusion, ticlopidine and clopidogrel selectively neutralize the ADP inhibition of PGE1-activated platelet adenylate cyclase in rats and rabbits.     

Fate of micelles and quantum dots in cells.

Micelles and quantum dots have been used as experimental drug delivery systems and imaging tools both in vitro and in vivo. Investigations of their fate at the subcellular level require different surface-core modifications. Among the most common modifications are those with fluorescent probes, dense-core metals or radionucleids. Cellular fate of several fluorescent probes incorporated into poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles were developed to explore micelle fate by electron microscopy. More recently, we have examined quantum dots (QDs) as the next-generation-labels for cells and nanoparticulate drug carriers amenable both to confocal and electron microscopic analyses. Effects of QDs at the cellular and subcellular levels and their integrity were studied. Results from different studies suggest that size, charge and surface manipulations of QDs may play a role in their subcellular distribution. Examples of pharmacological agents incorporated into block copolymer micelles, administered or attached to QD surfaces show how the final biological outcome (e.g. cell death, proliferation or differentiation) depends on physical properties of these nanoparticles.     

Decision trees based on automatic learning and their use in cardiology

Computerized information systems, especially decision support systems, have become an increasingly important role in medical applications, particularly in those where important decision must be made effectively and reliably. But the possibility of using computers in medical decision making is limited by many difficulties, including the complexity of conventional computer languages, methodologies and tools. Thus a conceptual simple decision making model with the possibility of automating learning should be used. In this paper we introduce a cardiological knowledge-based system based on the decision tree approach supporting the mitral valve prolapse determination. Prolapse is defined as the displacement of a bodily part from its normal position. The term mitral valve prolaps (PMV), therefore, implies that the mitral leaflets are displaced relative to some structure, generally taken to be the mitral annulus. The implications of the PMV are the following: disturbed normal laminar blood flow, turbulence of the blood flow, injury of the chordae tendinae, the possibility of thrombus's composition, bacterial endocarditis, and finally hemodynamic changes defined as mitral insufficiency and mitral regurgitation. Uncertainty persists about how it should be diagnosed and about its clinical importance. It is our deep belief that the echocardiography enables properly trained experts armed with proper criteria to evaluate PMV almost 100%. But unfortunately, there are some problems concerned with the use of echocardiography. In that manner we have decided to start a research project aimed at finding new criteria and enabling the general practitioner to evaluate PMV using conventional methods and to select potential patients from the general population. To empower one to perform needed activities we have developed a computer tool called ROSE (computeRised prOlaps Syndrom dEtermination) based on algorithms of automatic learning. This tool supports the definition of new criteria and the selection of potential PMV-patients.     

Somatosensory evoked potential monitoring during intracranial surgery

In the neurosurgical approach to intracranial aneurysms which are often accompanied by arterial spasm and cortical ischaemia, monitoring procedures aim to obtain useful information on cerebral function. SEPs evoked by stimulation of the median nerve at the wrist and of the tibial nerve at the medial malleolus were registered in 45 patients with intracranial aneurysms during neurosurgical procedures. Our results show SEP abnormalities during different stages of neurosurgical procedures in 36 patients out of the monitored 45. Significant abnormalities of SEPs with respect to the control group were decrease of the amplitude of N 20-P 25 complex, lengthening of the absolute latency of the waves N 20- and P 25 and lengthening of the central conduction time (CCT) (N 13-N 20). The greatest SEP abnormalities were registered during the neurosurgical approach to aneurysm and during the clipping procedure. However, the changes were reversible in the majority of the patients. The aim of this paper was to focus on early detection of some cerebral function disturbances during the neurosurgical procedure as well as the prevention of possible brain damage.