ABSTRACT
BACKGROUND: The consensus thrombin aptamer C15-mer is a single-stranded DNA of 15 nucleotides [d(GGTTGGTGTGGTTGG)] that was identified by the selection of thrombin-binding molecules from a large combinatorial library of oligonucleotides. It is capable of inhibiting thrombin at nanomolar concentrations through binding to a specific region within thrombin exosite 1. As has been shown in our earlier studies, the 4-thio-deoxyuridylate (s4dU)-containing oligonucleotides have high affinity for a number of proteins, due to the reduced hydrophilic character of the modified oligonucleotide. METHODS: Three different analogs of the original thrombin-inhibiting sequence, in which some of the thymidylate residues were replaced by 4-thio-deoxyuridylates, were synthesized. The inhibitory effect of modified aptamers was tested on thrombin-catalyzed fibrin clot formation and fibrinopeptide A release from fibrinogen, thrombin-induced platelet aggregation/secretion, and the formation of thrombus on coverslips coated with human collagen type III, thrombin-treated fibrinogen or subendothelial matrix of human microvascular endothelial cells. RESULTS: As compared with the C15-mer, the analog with the sequence GG(s4dU)TGG(s4dU)G(s4dU)GGT(s4dU)GG (UC15-mer) showed a 2-fold increased inhibition of thrombin-catalyzed fibrin clot formation, fibrinopeptide A release, platelet aggregation and secretion in human plasma and thrombus formation on thrombin-treated fibrinogen surfaces under flow conditions. Concerning the inhibition of thrombin-induced fibrin formation from purified fibrinogen and activation of washed platelets, UC15-mer was 3-fold and twelve-fold more effective than C15-mer, respectively. CONCLUSION: The replacement of four thymidylate residues in C15-mer by 4-thio-deoxyuridylate resulted in a new thrombin aptamer with increased anticoagulant and antithrombotic properties.
Subject(s)
Aptamers, Nucleotide/pharmacology , Blood Coagulation/drug effects , Platelet Aggregation/drug effects , Thrombosis/prevention & control , Aptamers, Nucleotide/chemical synthesis , Base Sequence , Deoxyuracil Nucleotides , Drug Evaluation, Preclinical , Endothelial Cells , Endothelium, Vascular/cytology , Fibrinopeptide A/metabolism , Humans , Perfusion , Structure-Activity Relationship , ThionucleotidesABSTRACT
This matched control group study assesses primary visual memory of stroke patients using the GEMAT visual-memory test. Primary visual memory of 29 stroke patients who scored 24 or more on the MMSE was compared with that of 33 age and sex-matched controls. Patients were recruited from physiotherapy outpatient clinics. Measured variables were the total time needed to complete the test (GTT) and the number of correct answers (GCA). Patients were slower (p < 0.01) and made more mistakes (p < 0.01) than controls. 'Young' (60-71) subjects made fewer mistakes (p < 0.01) than old subjects (72-89) and patients who scored 24-26 on MMSE were slower than patients who scored 27-30. It should be taken into consideration that stroke patients whose cognitive function is within a normal range of the MMSE might have impaired primary visual memory.
Subject(s)
Cerebrovascular Disorders/psychology , Memory , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Cerebrovascular Disorders/physiopathology , Educational Status , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychomotor Performance , Vision, OcularABSTRACT
The level and quality of concentration were tested before and after each lesson in one class session. Two of the four classes participated in physical education activities, and the other two studied science. Each subject matter was studied the beginning and at the end of the school day. The research design was 2 x 2 x 2 factorial (two subject matters, two times of the school day, and as a repeated measure two times of test for each group at the beginning and end of each lesson). The level and the quality of concentration found at the end of each lesson were significantly higher than at the beginning. The subject matters did not influence concentration. It may be concluded that the time of day was the main influence on concentration, so teachers' claims against physical education activity lessons can be rejected. The increase in concentration toward the end of the lesson implies the need for careful lesson planning or even the consideration of increasing duration of lessons.
Subject(s)
Attention , Physical Education and Training , Child , Discrimination Learning , Female , Humans , Male , Pattern Recognition, VisualABSTRACT
Two different measures were used to test field dependence-independence, Group Hidden Figures Test and Portable Rod and Frame Test. The purpose of the study was to compare the advantages of these two measures in differentiating among adolescents who are active in individual and team sports and those who are not. 94 adolescent boys and girls were divided into three groups, as follows: 33 in individual sports, 31 in team sports, and 30 nonathletes. No correlation was found between the two measures. The Portable Rod and Frame Test was the better instrument for distinguishing among the groups. This test requires use of visual vs proprioceptive information to perceive the body's spatial orientation. The Group Hidden Figures Test requires more analytical intelligence. Since there are relationships among awareness of the body, spatial orientation, and physical activity of athletes, the Portable Rod and Frame Test seems to be more applicable to the task of distinguishing between and among athletes and nonathletes.
