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Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS.

The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of macaques could be used as a model system to assess the role of selenium in AIDS. Plasma and serum selenium levels were determined by standard assays in monkeys before and after inoculation of SIV. SIV-infected cells or cells expressing the HIV Tat protein were labeled with 75Se, and protein extracts were prepared and electrophoresed to analyze selenoprotein expression. Total tRNA was isolated from CEMx174 cells infected with SIV or from KK1 cells infected with HIV, and selenocysteine tRNA isoforms were characterized by reverse phase chromatography. SIV-infected monkeys show a decrease in blood selenium levels similar to that observed in AIDS with development of SAIDS. Cells infected with SIV in vitro exhibit reduced selenoprotein levels and an accumulation of small molecular weight selenium compounds relative to uninfected cells. Examination of the selenocysteine tRNA isoforms in HIV-infected KK1 cells or SIV-infected CEMx174 cells reveals an isoform distribution characteristic of selenium-deficient cells. Furthermore, transfection of Jurkat E6 cells with the Tat gene selectively altered selenoprotein synthesis, with GPX4 and Sep15 being the most inhibited and TR1 the most enhanced. Taken together, the data show that monkeys infected with SIV in vivo and cells infected with SIV in vitro will provide appropriate models for investigating the mechanism(s) responsible for reduced selenium levels that accompany the progression of AIDS in HIV disease.

Acquired Immunodeficiency Syndrome↗

An essential role of s-adenosyl-L-methionine:L-methionine s-methyltransferase in selenium volatilization by plants. Methylation of selenomethionine to selenium-methyl-L-selenium- methionine, the precursor of volatile selenium.

Selenium (Se) phytovolatilization, the process by which plants metabolize various inorganic or organic species of Se (e.g. selenate, selenite, and Se-methionine [Met]) into gaseous Se forms (e.g. dimethylselenide), is a potentially important means of removing Se from contaminated environments. Before attempting to genetically enhance the efficiency of Se phytovolatilization, it is essential to elucidate the enzymatic pathway involved and to identify its rate-limiting steps. The present research tested the hypothesis that S-adenosyl-L-Met:L-Met S-methyltransferase (MMT) is the enzyme responsible for the methylation of Se-Met to Se-methyl Se-Met (SeMM). To this end, we identified and characterized an Arabidopsis T-DNA mutant knockout for MMT. The lack of MMT in the Arabidopsis T-DNA mutant plant resulted in an almost complete loss in its capacity for Se volatilization. Using chemical complementation with SeMM, the presumed enzymatic product of MMT, we restored the capacity of the MMT mutant to produce volatile Se. Overexpressing MMT from Arabidopsis in Escherichia coli, which is not known to have MMT activity, produced up to 10 times more volatile Se than the untransformed strain when both were supplied with Se-Met. Thus, our results provide in vivo evidence that MMT is the key enzyme catalyzing the methylation of Se-Met to SeMM.

Adaptation, Physiological↗

Incorporation of selenium-75 into seminal plasma and spermatozoa of the bull.

75Se was given intravenously into 5 bulls. Multiple blood and semen samples were taken and during slaughter 5, 10, 15, 20 and 80 days later samples of various reproductive and other organs were collected. After injection, 75Se in blood reached a peak at 6 h followed by a rapid decline. The label was mainly found in serum with very low levels in erythrocytes. Initially the serum 75Se was bound to a macromolecule with a mw of 80 kDa, but later a larger molecule (100 kDa) was observed. In semen 75Se was first mainly found in seminal plasma, where a plateau level was reached at 5 d followed by a gradual decline after 12 d. The total semen level, however, increased after 14 d and this increase was due to a rapid appearance of the label in spermatozoa. The sperm 75Se level reached a plateau at 20 d and remained high until 40 days, after which a gradual decline ensued. The seminal plasma 75Se eluted in gel filtration coincident with glutathione peroxidase. The highest levels of 75Se were found in the kidney followed by seminal vesicles and testicles. The seminal vesicle secretion was particularly rich in 75Se and its fractionation resembled that of the seminal plasma. 75Se appeared in the epididymal caput within 5 days and passed through the epididymis in 20 days. It is concluded that 75Se is actively incorporated in the bull seminal vesicles into GSH-Px, while in the testis it is incorporated into a structural sperm protein during spermatogenesis.

Animals↗

Computed and conventional chest radiography: a comparison of image quality and radiation dose.

The aim of this study was to compare the image quality and entrance skin dose (ESD) for film-screen and computed chest radiography. Analysis of the image quality and dose on chest radiography was carried out on a conventional X-ray unit using film-screen, storage phosphor plates and selenium drum direct chest radiography. For each receptor, ESD was measured in 60 patients using thermoluminescent dosemeters. Images were printed on 35 x 43 cm films. Image quality was assessed subjectively by evaluation of anatomic features and estimation of the image quality, following the guidelines established by the protocols of the Commission of the European Communities. There was no statistically significant difference noted between the computed and conventional images (Wilcoxon rank sum test, P > 0.05). Imaging of the mediastinum and peripheral lung structures were better visualized with the storage phosphor and selenium drum technique than with the film-screen combination. The patients' mean ESD for chest radiography using the storage phosphor, film-screen combination and selenium drum was 0.20, 0.20 and 0.25 mGy, respectively, with no statistically significant difference with P > 0.05 (chi(2) tests).

Humans↗

Bile acid malabsorption in HIV infected patients with chronic diarrhoea.

AIMS: To look for the presence of bile acid malabsorption in HIV infected patients with chronic diarrhoea and determine whether bile sequestering agents may have a role in palliating this common problem. METHODS: Nineteen HIV infected patients with chronic diarrhoea (duration > one month) poorly controlled on conventional treatment were investigated using the seven day retention of 75seleno-23-homocholic acid taurine (SeHCAT) as a measure of bile acid loss from the enterohepatic circulation. Patients with evidence of bile acid malabsorption were offered cholestyramine. RESULTS: Sixteen (84%) had evidence of bile acid malabsorption (< 15% retention at seven days). Ten of the 16 patients with bile acid malabsorption had terminal ileal biopsies-six had ileitis and four normal histology, suggesting that malabsorption is not always related to terminal ileitis. Thirteen patients with bile acid malabsorption have been treated with cholestyramine and 11 have reported a symptomatic response. CONCLUSIONS: Bile acid malabsorption can be demonstrated in some cases of HIV associated chronic diarrhoea and we suggest a therapeutic trial of a bile sequestering agent in patients whose symptoms are not well controlled using conventional anti-diarrhoeal agents.

Adult↗

Bile acid malabsorption: a complication of conduit surgery.

We examined the possibility that use of a section of the terminal ileum for ileal conduit construction may impair bile acid absorption and cause choloretic diarrhoea. Nineteen normal subjects (mean age 41 years) and 16 patients with conduits (mean age 47 years) were investigated using the SeHCAT retention test. Conduit patients showed significant impairment of SeHCAT retention compared with normal subjects; 82% of patients had a retention below the lower limit of normal. The mean bowel frequency of patients during the test was 3 motions/day this being significantly different from their pre-operative bowel habit. It was concluded that the use of the terminal ileum in conduit construction may impair bile acid absorption, as measured by the SeHCAT retention test, and may cause an increase in bowel frequency.

Adult↗