The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina

Background

Anti-ischaemic effect of A1 adenosine receptor agonists was shown in animal and preclinical studies. The present proof-of-concept study aimed at evaluation of the efficacy and safety of a new adenosine A1 receptor agonist capadenoson in patients with stable angina.

Methods

This was a randomized, double-blind, placebo-controlled, single dose-escalating, multicenter trial comparing the effect of capadenoson at 1, 2.5, 5, 10, and 20?mg versus placebo. For each dose step patients were randomized to receive single doses of either capadenoson or matching placebo in a 5:1 ratio. The primary efficacy variable was the absolute difference in heart rate (HR) at maximum comparable level of workload between baseline and post dose exercise tolerance test at maximum concentration of capadenoson. Capadenoson effect on total exercise time and time to 1-mm ST-segment depression were also measured.

Results

Sixty-two male patients with stable angina were enrolled in the study. There was a consistent trend for HR reduction at comparable maximum work load in active treatment groups, with significant differences against placebo for 10 and 20?mg (HR reduction by 12.2 and 6.8 beats per min, p?=?0.0002 and p?=?0.032, respectively). A statistically significant trend (p?=?0.0003) for a reduction in HR with increasing doses of capadenoson was shown. Increases in total exercise time and time to 1-mm ST-segment depression were also observed.

Conclusions

In patients with stable angina capadenoson lowers exercise HR at comparable maximum workload, which is associated with improved total exercise time and prolongation of time to ischaemia.     

常用抗高血压药物对血压的时间生物学特征的影响

目的 :探讨 3类常用抗高血压药物对非杓型的高血压病患者BP的时间生物学特征的影响。方法 :共入选非杓型BP分布的高血压病患者 16 1例 ,将其随机分为 3组 ,分别给予赖诺普利 (10mg·d-1) ,非洛地平 (2 5mg·d-1) ,或氢氯噻嗪 (5 0mg·d-1) ,并于治疗前后行 2 4h动态BP监测。采用余弦拟合方法分析治疗前后患者BP时间生物学特征的改变。结果 :赖诺普利组与非洛地平组治疗后 2 4hBP均值明显降低 ,但其振幅、峰值相位无变化 ;氢氯噻嗪治疗降压效果不甚理想 ,但显著增加了患者BP的夜间降低幅度 ,使患者BP由非杓型转变为杓型分布。结论 :氢氯噻嗪治疗可能使非杓型分布的高血压病患者的BP转变为杓型分布 ,从而有助于降低患者相关并发症的发生率。     

Effets du repas précompétitif sur la perception de l'effort et sur la glycémie lors d'un exercice de pédalage

The first purpose of the present study was to investigate the effect of three different preexercise meals on perceived exertion and glycaemia during a one-hour bicycle exercise at 80% VO₂ max. The second purpose of this study was to determine the relationship between glycaemia and perceived exertion. Eight athletes (age: 24.6 ± 2.7 years, weight: 78.0 ±6.8 kg, height: 182.6 ± 9.9 cm) completed three assessment sessions, each being preceeded by one of the following meals, ingested 3 h before exercise: 400 mL of water, 400 mL of water and 75 g of glucose, and 100 mL of water and 375 g of potatoes. The subjects 'perceived exertion were measured at times 6, 15, 30, 45, 60 min and glycaemia at 0, 30, 60 min of the exercise. The results showed that perceived exertion (RPE and ETL) of each meal increased as a function of time (P <- 0.05) whereas glycaemia did not differ except for the glucose meal between 30 min and 1 h(P < 0.02). There was no significant difference in ratings of perceived exertion among any meal whereas glycaemia was different between the three conditions only at the beginning and the middle of the exercises (P < 0.04 and P < 0.02, respectively). Moreover, the vectorial angles between the variables ofperceived exertion and the glycaemia are close to 90 °. These results would suggest that perceived exertion does not seem to be affected by the three preexercise meals used in our study. Perceived exertion is not correlated to glycaemia changes during one-hour high intensity exercise. The results would, therefore, suggest that glycaemia is not a contributor signal of perceived exertion in this study. It seems that physiological factors other than glycaemia may have mediated the perceptual intensity at exhaustion. The respiratory-metabolic signals of exertion which are most pronounced at high relative exercise intensity are suggested to influence the perceptual signal of exertion.     

Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells

Fusion proteins present in leukemic cells frequently contain a new amino acid at the fusion point. We tested whether a peptide (BCR1/25) encompassing the fusion region of the hybrid molecule pml/RAR alpha, which is selectively expressed by acute promyelocytic leukemia (APL) cells, can be recognized by human T lymphocytes in vitro. CD4+ lymphocytes, at both polyclonal and clonal level, recognized peptide BCR1/25 in an HLA-DR--restricted fashion on presentation by autologous antigen-presenting cell (APC) or by APC expressing the HLA-DR11 restricting molecule. Control peptides corresponding to the normal pml and RAR alpha proteins were not recognized. One clone (DEG5) also exerted a high and specific cytotoxicity against autologous cells pulsed with BCR1/25. The autologous DE LCL containing a transduced pml/RAR alpha fusion gene and expressing a bcr1 type of the pml/RAR alpha hybrid protein induced the proliferation of DE anti-BCR1/25 T cell clones. It is concluded that the bcr1 type-pml/RAR alpha fusion protein of APL contains an antigenic site, absent from the normal parent molecules and recognized by human CD4+ lymphocytes.     

Abnormal autonomic control of the cardiovascular system in syndrome X

Anomalies of autonomic control of the coronary circulation may play a role in the development of syndrome X (angina pectoris, ischemia-appearing results on exercise test, and normal coronary arteriograms). Twenty-six patients with syndrome X and 20 healthy sex- and age-matched control subjects were studied by means of analysis of heart rate variability during 24-hour Hotter monitoring. Spectral and nonspectral parameters of heart rate variability were investigated. Mean heart rate was similar in patients with syndrome X and in control subjects. Patients with syndrome X had significantly lower standard deviation of all normal RR intervals, a lower percentage of adjacent normal RR intervals >50 ms in difference (126.4 ± 22 vs 149 ± 43 ms, p <0.05; 6.3 ± 4 vs 11.2 ± 7%, p <0.05; respectively), and a trend toward lower values of time-domain parameters. Lower values of total power and low frequency were also observed in patients with syndrome X (1273 ± 693 vs 1790 ± 989 ms², p <0.05; 406 ± 176 vs 729 ± 455 ms², p <0.01, respectively). An inverse correlation between heart rate and measures of heart rate variability was found in syndrome X but not in control subjects. High- and low-frequency power showed a similar circadian pattern in syndrome X patients and control subjects. Patients and control subjects were then allocated into 2 groups according to the median RR duration: syndrome X1 and control 1 with high mean heart rate, and syndrome X2 and control 2 with low mean heart rate. The syndrome X1 group had a significantly lower standard deviation of all normal RR intervals, root-mean-square difference of successive RR intervals, percentage of adjacent normal RR intervals >50 ms different, and high and low frequency than did the syndrome X2, control 1, and control 2 groups. In conclusion, patients with syndrome X have a sympathovagal balance shifted toward sympathetic predominance that is more evident in those with an increased mean heart rate. This dysfunction appears to persist throughout the 24 hours and may indicate heterogeneity in autonomic function in syndrome X.