Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril.

OBJECTIVE: To compare the efficacy, safety and tolerability of valsartan to an angiotensin-converting enzyme (ACE) inhibitor, lisinopril, and placebo in patients with mild-to-moderate essential hypertension. DESIGN: A total of 734 men and women were randomised in this multicentre, double-blind, optional titration, parallel group trial. Volunteers received valsartan 80 mg (n = 364), lisinopril 10 mg (n = 187) or placebo (n = 183) daily for 4 weeks, with subsequent titration of dose depending on response to treatment (valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily, lisinopril 10 mg titrated to lisonopril 20 mg once daily). Patients were assessed at 4, 8 and 12 weeks. MAIN OUTCOME MEASURES: The primary variable was change from baseline in mean sitting diastolic blood pressure (SDBP). Other efficacy variables included sitting systolic blood pressure (SSBP) and percentage of 'successful' responders (SDBP <90 mm Hg or > or =10 mm Hg reduction from baseline). RESULTS: All active treatment groups were shown to demonstrate significant reductions in SDBP compared to placebo at endpoint of therapy (least mean square reduction from baseline: valsartan 80/160 mg: -5.25 mm Hg (Cl -7.17, -3.34, P< 0.001); valsartan 80/80 mg twice daily: -5.63 mm Hg (Cl -7.51, -3.75, P< 0.001); lisinopril 10/20 mg: -6.93 mm Hg, (Cl -8.81, -5.05, P< 0.001). There were no statistically significant differences between the active treatment groups at endpoint of therapy. In patients requiring titration to a higher dose (placebo n = 142, valsartan 80/80 twice daily n = 124, valsartan 80/160 n = 114, lisinopril 10/20 n = 120), there were no significant treatment differences between valsartan 160 mg given as a single daily dose or as 80 mg twice daily (P = 0.658). Both valsartan and lisinopril produced similarly high percentages of 'successful' responders at endpoint of therapy. A somewhat higher frequency of drug related cough was observed in lisinopril treated patients (8%) compared to valsartan (1.1%) or placebo (0.5%). CONCLUSIONS: Valsartan 80 mg daily, with titration to 160 mg daily as required, provides similar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily. Valsartan provides a new antihypertensive agent with comparable efficacy to lisinopril and appears to be associated with a reduced incidence of cough.

Acquired color vision defects and self monitoring of blood sugar in diabetics.

Color vision defects are common in diabetic patients and may precede visible retinal changes. More severe retinopathy is generally associated with more severe color vision defects. Many diabetics err when making color comparisons using self monitoring techniques. Optometrists can play an important role in diabetes patient management by monitoring color vision defects and making patients aware of problems or potential problems in self monitoring. Care must be taken in color vision evaluation as the most frequent acquired color vision defect in diabetics is a blue-yellow axis defect. Most commonly employed color vision tests are not sensitive in detecting this defect.

Iron--dioxygen-dependent changes to the biological activities of bleomycin.

Antitumor antibiotic bleomycin can bind to and degrade DNA, both in vivo and in vitro. This DNA damaging property in vitro can be related to its ability to chelate ferrous ions under aerobic conditions leading to the formation of "active oxygens," which are thought to be directly responsible for the damage. At present, evidence points to the hydroxyl radical formed by an iron-catalyzed Haber-Weiss reaction as the free radical most likely to be involved in this damage. When these same reactions occur in the absence of DNA, the free radicals then damage the bleomycin molecule, resulting in changes to its DNA-degrading activity, antibacterial properties, and chemical composition. Attempts to protect both bleomycin and DNA with a variety of specific and nonspecific scavengers have been unsuccessful, with several even showing pro-oxidant activity towards the iron-dependent damage. Only the metal chelators were effective inhibitors of bleomycin-iron-dependent damage to DNA. The damaged bleomycin lost some 50% of its ability to degrade DNA in vitro. This activity was closely paralleled by a loss in antibacterial activity against two different strains of bacteria.

Characterization of a Gibberellin-Insensitive Dwarf Wheat, D6899 : EVIDENCE FOR A REGULATORY STEP COMMON TO MANY DIVERSE RESPONSES TO GIBBERELLINS.

The effects of gibberellin in two wheat varieties, Nainari 60 and D6899, have been studied. D6899 is a dwarf wheat having a single locus mutation, the Rht 3 gene ("Tom Thumb" gene), which is located on chromosome 4A. When compared with the standard height wheat variety, Nainari 60, D6899 does not have a slowdown in cellular metabolism such as respiration rate, protein content, rate of protein synthesis, and uptake of amino acids. The content of ATP is even higher in D6899. However, all of the gibberellin-mediated physiological processes that we have studied, including leaf elongation, synthesis and release of hydrolytic enzymes, and secretion of phosphate ions and reducing sugars in aleurone layers, are retarded in D6899. D6899 and Nainari 60 have essentially the same uptake and metabolism of gibberellin and their levels of endogenous inhibitors such as abscisic acid do not differ drastically. The dosage-response curve of the gibberellin-mediated alpha-amylase production indicates that a rate-limiting step, which is common to many of the diverse gibberellin responses, is partially blocked in D6899 wheat.