Therapeutic potential of selective superoxide dismutase mimetics

Selective superoxide dismutase (SOD) mimetics are potentially useful in pathological conditions in which there is an overproduction of the superoxide anion O-2.(-). These pathological conditions include inflammation, ischemia/reperfusion, shock, various cardiovascular disorders, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. A major step forward in this field was the development of small-molecule selective SOD mimetics that penetrate cell membranes, These selective SOD mimetics catalytically remove O-2.(-) without interfering with nitric oxide (NO), peroxynitrite (ONOO-) or other radicals such as hydroxyl radical or hydrogen peroxide (H2O2). These selective SOD mimetics (SC-52608, SC-55858, M-40403 and M-40401) have been shown to have benefits in animal models of inflammation, ischemia/reperfusion, shock, thrombosis and diabetes. The next challenge with selective SOD mimetics is to develop therapeutic potential into therapeutic agents.

Selective ingestion of pelagic versus benthic algae by the cockle Cerastoderma edule (Linne, 1758)

The pre-ingestive selection of microphytobenthic algae by the cockle Cerastoderma edule was studied in comparison with diets containing the pelagic diatom Phaeodactylum tricomutum. Treatments with the different diets covered a range of seston concentrations and organic content similar to field conditions. Rejection rates of C. edule exposed to the different treatments were significantly correlated with the concentration of total particulate matter. No significant differences in total rejection rates were found between pelagic and benthic diets. Organic rejection rate was significantly correlated with particulate organic matter of the treatments and no significant differences were found between both diets. Selection efficiency was significantly correlated with particulate organic matter concentration in both diets and no significant differences were found between the diets. Analysis of the pseudofeces composition by flow cytometry from cockles exposed to a mixed diet of microphytobenthic algae and P. tricornutum, showed a preferential ingestion of the pelagic diatom. Benthic species, such as small pennates and Navicula sp., were preferentially ingested in comparison to larger microphytobenthic species. The largest microphytobenthic species, Cylindrotheca sp., was significantly rejected. In general, C. edule is an opportunistic filter feeder that takes advantage of both pelagic and benthic algal cells.

Effect of changing data collection parameters on statistical motor unit number estimates

The effect of number of samples and selection of data for analysis on the calculation of surface motor unit potential (SMUP) size in the statistical method of motor unit number estimates (MUNE) was determined in 10 normal subjects and 10 with amyotrophic lateral sclerosis (ALS). We recorded 500 sequential compound muscle action potentials (CMAPs) at three different stable stimulus intensities (10–50% of maximal CMAP). Estimated mean SMUP sizes were calculated using Poisson statistical assumptions from the variance of 500 sequential CMAP obtained at each stimulus intensity. The results with the 500 data points were compared with smaller subsets from the same data set. The results using a range of 50–80% of the 500 data points were compared with the full 500. The effect of restricting analysis to data between 5–20% of the CMAP and to standard deviation limits was also assessed. No differences in mean SMUP size were found with stimulus intensity or use of different ranges of data. Consistency was improved with a greater sample number. Data within 5% of CMAP size gave both increased consistency and reduced mean SMUP size in many subjects, but excluded valid responses present at that stimulus intensity. These changes were more prominent in ALS patients in whom the presence of isolated SMUP responses was a striking difference from normal subjects. Noise, spurious data, and large SMUP limited the Poisson assumptions. When these factors are considered, consistent statistical MUNE can be calculated from a continuous sequence of data points. A 2 to 2.5 SD or 10% window are reasonable methods of limiting data for analysis. Muscle Nerve 27: 320–331, 2003

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients

Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.

Selective entrainment of sediment graded by size and density under waves

The influence of near-bed sorting processes on heavy mineral content in suspension is discussed. Sediment concentrations above a rippled bed of mixed quartz and heavy mineral sand were measured under regular nonbreaking waves in the laboratory. Using the traditional gradient diffusion process, settling velocity would be expected to strongly affect sediment distribution. This was not observed during present trials. In fact, the vertical gradients of time-averaged suspension concentrations were found to be similar for the light and heavy minerals, despite their different settling velocities. This behavior implies a convective rather than diffusive distribution mechanism. Between the nonmoving bed and the lowest suspension sampling point, fight and heavy mineral concentration differs by two orders of magnitude. This discrimination against the heavy minerals in the pickup process is due largely to selective entrainment at the ripple face. Bed-form dynamics and the nature of quartz suspension profiles are found to be little affected by the trialed proportion of overall heavy minerals in the bed (3.8-22.1%).