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Aim: To test the effects of atenolol and amlodipine, either alone or in combination, on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS), and the prevalence of stroke in stroke-prone spontaneously hypertensive rats (SHR-SP). Methods: In the first set of the study, 24 8-month-old, female SHR-SP rats were randomly divided into 3 groups. Blood pressure, heart period, and BRS were determined before and after the intragastric administration of atenolol (10 mg/kg) and amlodipine (1.0 mg/kg), either alone or in combination. In the second set of the study, 40 male and 40 female rats were randomly assigned to 1 of the following 4 groups: control, atenolol (10 mg·kg ), and both (10 male and 10 female in each group). The stroke incident and survival time were recorded. Results: Atenolol and amlodipine, either alone or in combination, significantly decreased blood pressure, with the exception of the amlodipine-induced effect on diastolic blood pressure. Meanwhile, only the combination treatment significantly decreased the BPV levels for the same period. The q-values calculated by the probability sum analysis were 1.17 and 2.67 for systolic and diastolic blood pressure, respectively, and were 2.48 and 2.10 for systolic and diastolic BPV, respectively, following administration. Neither drug exhibited any significant effect on BRS. Atenolol and amlodipine, either alone or in combination, significantly increased the lifespan of SHR-SP, with the best effect elicited by the combination therapy. Conclusion: A significant synergism exists between atenolol and amlodipine in lowering and stabilizing blood pressure in SHR-SP. Combination therapy may be an optimal strategy for the prevention of stroke in hypertension. Key wordsstroke; hypertension; stroke-prone; spont a ne ou sl yhy per t ensi ve r a t s ; a t eno l ol ; amlodipine; blood pressure; blood pressure variability

Aim: To test the synergistic effects of atenolol and amlodipine on lowering blood pressure (BP) and reducing blood pressure variability (BPV) in 2-kidney, one-clip (2K1C) renovascular hypertensive rats. Methods: Forty-eight 2K1C renovascular hypertensive rats were randomly divided into 6 groups. They were respectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10.0 mg/kg), amlodipine (1.0 mg/kg), and combined atenolol and amlodipine (low dose: 5.0+0.5 mg/kg; intermediate dose: 10.0+1.0 mg/kg; high dose: 20.0+2.0 mg/kg). The drugs were given via a catheter in a gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration. Results: Compared with BP before medication, all 3 doses of combined atenolol and amlodipine significantly decreased the BP at 24 h after administration, except for the low dose on diastolic BP. Compared with the control group, all 3 doses of combined atenolol and amlodipine significantly reduced the average BP levels for the 24 h period after administration; furthermore, the high and intermediate doses also significantly decreased the BPV levels for the same period. The q values calculated by probability sum analysis for systolic and diastolic BP for the 24 h period after administration were 2.29 and 1.45, respectively, and for systolic and diastolic BPV for the same period they were 1.41 and 1.60, respectively. Conclusion: There is significant synergism between atenolol and amlodipine in lowering and stabilizing BP in 2K1C renovascular hypertensive rats.

low affinity of insulin detemir for the IGF-1 receptor (approximately one-tenth of that of human insulin) [1] could prove beneficial in the treatment of pregnant women, particularly as regards the effect on birthweight and maternal complications. Thus, to determine the drug's safety in pregnancy, we focused first on congenital malformations, given that all the women used insulin detemir during the period of embryogenesis [4]: our findings seem to exclude any effect on embryo-foetal development.Another issue is the potential effect on foetal growth. One concern is that the affinity of insulin analogues for the IGF-1 receptor could potentially cause foetal macrosomia. In our series, however, the use of insulin detemir throughout pregnancy was not associated with a higher birthweight or any changes in neonatal outcome. In addition, the prevalence of macrosomia and ⁄ or large for gestational age (LGA) was within the range for Type 1 diabetic women using other forms of insulin [5]. This study was performed in a small cohort of women, but it is the first report on the use of insulin detemir in human pregnancy. Judging from our results, insulin detemir seems to help improve glycaemic control and does not appear to have any adverse effects on maternal or foetal outcome in Type 1 diabetic women. Studies on larger series of patients and randomized controlled trials are warranted to further assess the safety and effectiveness of insulin detemir in pregnancy. References1 Home P, Bartley P, Russell-Jones D, Hanaire-Broutin E, Heeg JE, Abrams P et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial.We agree with the observations made by Dalan et al.[1] on the inappropriate autonomic and adrenergic responses to severe hypoglycaemia in sulphonyurea overdose. We describe our experience with a 16-year-old boy who was admitted in a comatose state as a result of gliclazide-induced hypoglycaemia.He was an orphan living with a guardian (maternal uncle). Apart from mild learning difficulties, he had no known medical illnesses and was not on any regular medications. On the day of admission, he was noted by his guardian to be restless in his sleep and unable to be aroused. No abnormal behaviour was noted the day before, nor did he complain of hunger, sweating, palpitations, anxiety or other adrenergic symptoms before he went to bed at his usual time. He was very restless when he was first seen in the emergency department of a district general hospital. Vital signs were within the normal range (blood pressure 120 ⁄ 80 mmHg, pulse 82 b ⁄ min, regular) except for very low capillary blood glucose (undetectable on the glucose meter). In view of the restlessness and persistent hypoglycaemia, multiple boluses of i.v. dextrose 50% and i.v. benzodiazepines (midazolam) were given. He was then referred to our hospital for further management. Upon arrival, his Glasgow Coma Scale was 5 ⁄ 15 with oxygen saturation of 75-80% on room air, blood pressure 110 ⁄ 84 mmHg,...