Gradual reactivation of vascular angiotensin I to angiotensin II conversion during chronic ACE inhibitor therapy in patients with diabetes mellitus.

AIMS/HYPOTHESIS: In chronic heart failure there is gradual reactivation of vascular tissue angiotensin I (AI) to angiotensin II (AII) conversion over time in patients taking chronic ACE inhibitor therapy. However, it remains unknown whether the same overall phenomenon occurs in other patients taking chronic ACE inhibitor therapy, such as patients with type 2 diabetes mellitus. METHODS: We studied 30 patients with type 2 diabetes mellitus (mean age 43.5 +/- 10.8 years), all of whom received lisinopril (20 mg/day) as part of their normal treatment. Over the course of the 18 month study, we made measurements at 0, 9 and 18 months. These measurements included plasma values for components of the renin-angiotensin-aldosterone system. In addition, we infused AI and AII into the brachial arteries of patients to assess vascular tissue AI to AII conversion. RESULTS: There were no significant changes in plasma renin activity, ACE, AI, AII or aldosterone during the study. In contrast, vascular AI to AII conversion was significantly (p = 0.01) greater at 18 months than at 0 months. There was no change over time in the response to infused AII. CONCLUSIONS/INTERPRETATION: We have shown in vivo that vascular tissue AI to AII conversion gradually increases over time in patients with type 2 diabetes being treated with lisinopril. Further studies are required to determine whether this reactivation detracts from the cardioprotective effects of chronic ACE inhibitor therapy in diabetic patients, and if so, how best to overcome it.

A rare case of multiple right heart myxomas.

Primary tumours of the heart are rare. Myxomas are the most common primary cardiac tumours with an estimated incidence of 0.5 per million population per year. Myxomas are most commonly found in left atrium and are solitary in more than 90% cases. Familial myxomas are rarer and tend to be multiple. We report a rare case of multiple myxomas in the right heart which occurred sporadically, presenting with an episode of pre-syncope.

Determination of lactic acid and poly(lactic acid)s in a dermatological formulation by capillary electrophoresis.

A stability-indicating capillary electrophoresis (CE) method was developed to determine lactic acid at a level of 0.9% m/m in a dermatological formulation. This level includes up to 34% present in the form of poly(lactic acid)s. Current methods which involve treatment of samples with sodium hydroxide to hydrolyse the various lactic acid oligomers to free lactic acid cannot strictly be regarded as true measures of stability. The harsh hydrolysis conditions used can also lead to the generation of many degradation peaks from excipients such as natural extracts which can interfere with the detection of lactic acid in HPLC and CE methods. Application of indirect UV detection using 4-methoxybenzoic acid (p-anisate) as the background electrolyte and negative voltage polarity (detector towards anode) allows the direct quantification of the total available lactic acid from the monomer and the predominant linear oligomers in the raw material, i.e., the dimer (lactoyllactate) and the trimer. Tetradecyltrimethylammonium bromide was used as the electroosmotic flow modifier, lactic acid, lithium salt, as a calibration standard and butyric acid as an internal standard. A typical RSD for standard response using migration time-corrected peak area ratios was 1.17% (n = 9). Duplicate analysis of total lactic acid from two similar product placebos spiked with raw material gave average recoveries of 101.0 and 99.6%. The method, when applied to fully and partially hydrolysed raw material, showed good agreement (99.6%) with a standard titration assay for raw materials and was successfully applied to 5 month storage samples of a product. Advantages of the method include speed, simplicity, low consumption of reagents and no organic solvents.