Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised 'anti-coagulant' effects of dipyridamole in ischaemic CVD.

Interruptions in single strands of the DNA in slime mold and other organisms.

The molecular weight of single-stranded DNA from the slime mold Physarum polycephalum has been determined by alkaline gradient centrifugation. The average molecular weight during DNA synthesis ( approximately 1.5 x 10(7) D) is less than that observed in nonsynthetic periods ( approximately 4 x 10(7) D). On the basis of a chromosome number of 50 per nucleus and a DNA content of 1 mumug per nucleus, we are led to conclude that at pH 12 each chromosome dissociates into 300 (single-stranded) pieces of DNA. We have also compared the sedimentation profiles of single-stranded DNA from Escherichia coli, PPLO, and T2 bacteriophage. These data support the conjecture that each bacterial chromosome can be dissociated into 10 or 12 single-stranded pieces of DNA. Dissociation of DNA into multiple pieces under our experimental conditions is best interpreted in terms of interruptions in the continuity of the DNA either by naturally occurring gaps or at alkali-labile bonds.

Breakdown of DNA in x-irradiated Escherichia coli.

A comparison of differences in incorporation and loss of radio-activity between two strains of Escherichia coli shows that: (a) three times as much irradiation is necessary to produce the same reduction in incorporation of H(3)-thymidine in B/r, the resistant strain, as in B(s - 1), the sensitive one; (b) radioactivity is lost from the DNA of previously labeled bacteria during the first few cell generations after X-ray exposure, and even though the initial rate of loss is similar for all strains, the sensitive one loses much more label; (c) loss of DNA is a complicated function of dose. Losses increase with dose up to 25 or 50 kr in both strains; with higher doses, losses decrease in B(s - 1) but are unchanged in B/r. Since in both strains labeled RNA is retained in irradiated cells, lysis has not occurred but the DNA is broken down into small pieces which leak from each cell. Losses from either strain do not occur at ice-bath temperature, indicating that breakdown is a function of metabolic processes. A proposed mechanism for X-ray damage and repair is advanced.