Shikonin, an ingredient of Lithospermum erythrorhizon induced apoptosis in HL60 human premyelocytic leukemia cell line.

Apoptosis is a new therapeutic target of cancer research. Shikonin isolated from Lithospermum erythrorhizon, a traditional oriental medicinal herb, was observed to induce apoptosis in HL60 human premyelocytic leukemia cell line. Shikonin induced DNA fragmentation into the multiples of 180 bp and increased the percentage of hypodiploid cells in flow cytometry after propidium iodide staining. The increase of apoptotic cells was preceded by the activation of caspase-3, which was reported to play a central role in apoptotic process. The DNA fragmentation induced by shikonin was completely inhibited by the pretreatment of z-VAD-fmk, a specific inhibitor of caspase, clearly showing that the mode of cell death is apoptotic.

Antihypertensive efficacy and tolerability of once daily losartan potassium compared with captopril in patients with mild to moderate essential hypertension.

INTRODUCTION: Losartan potassium, an orally active, highly selective AT1 angiotensin II receptor inhibitor, effectively reduces blood pressure by direct receptor blockade, thereby lessening the likelihood of angiotensin converting enzyme (ACE) inhibitor-associated side effects such as dry cough or possibly angioedema. STUDY DESIGN: In this multinational, double-blind, randomized, parallel study, the efficacy and tolerability of once-daily losartan (50 mg) versus once-daily ACE inhibitor (captopril; 50 mg) was evaluated in 163 patients with mild to moderate hypertension. Non-responders after a 6-week treatment period had the dosage doubled for both study drugs until the end of study (week 12). RESULTS: Mean reductions in trough sitting diastolic blood pressure were significantly greater in the losartan group at week 6 (7.8 mmHg) and week 12 (9.1 mmHg) than in the captopril group (5.2 and 5.7 mmHg, respectively). Losartan and captopril were well tolerated. Headache was the most common adverse event reported in both groups. CONCLUSIONS: It was concluded that a once-daily administration of losartan was significantly more effective in this study in lowering sitting diastolic blood pressure than once-daily administration of captopril in patients with mild to moderate essential hypertension. Both losartan and captopril regimes were well tolerated.

Efficacy and tolerability of losartan potassium and atenolol in patients with mild to moderate essential hypertension.

The objective of this study was to compare the antihypertensive efficacy and tolerability of losartan potassium (losartan) and atenolol in patients with mild-to-moderate essential hypertension. This was a multinational, prospective, randomized, 12-week double-blind parallel study with a follow-up of 4 to 10 days posttreatment to assess any adverse effects of abrupt therapy withdrawal. Two hundred two patients were randomized (2:1) to treatment with losartan or atenolol, 50 mg once daily. Patients were titrated after 6 weeks to 100 mg once daily if their blood pressure was uncontrolled (sitting diastolic blood pressure > or = 90 mm Hg). Trough sitting diastolic blood pressure reductions at weeks 6 and 12 were similar in both the losartan (-9.2 mm Hg and -8.3 mm Hg) and atenolol (-10.8 mm Hg and -10.1 mm Hg) groups and a similar percentage of patients responded to each drug. Both agents were generally well tolerated, although eight patients (two patients taking losartan, and six taking atenolol) were withdrawn because of clinical adverse events (P < or = .05). Reduction in pulse rate from baseline averaged 10 beats/min in the atenolol group with no pulse rate reduction observed in the losartan group (P < .01). No evidence of rebound hypertension was observed in either group. In conclusion, losartan was as efficacious as atenolol in blood pressure reduction, and was at least as well tolerated.