Iodine-131-metaiodobenzylguanidine dosimetry in cancer therapy: risk versus benefit

In the treatment of neural crest tumors, such as pheochromocytoma, with[131I]MIBG, bone marrow toxicity limits the amount of administered activity and, thus, a therapeutically useful tumor dose. METHODS: We calculated tumor doses in a series of diagnostic studies with [123I]MIBG using accurate quantification of SPECT and planar scintigraphy. By extrapolating diagnostic results to therapeutic activities of [131I]MIBG, we could compare the results with whole-body doses from a series of therapies. RESULTS: The tumor dose was DT = 2.2 mGy MBq(-1) (median value of 27 measurements, range 0.04 < or = DT < or = 20 mGy MBq(-1) and the whole-body dose in a series of 16 patients undergoing 50 therapies was DWB = 0.12 +/- 0.04 mGy MBq(-1) (mean +/- s.d.). The therapeutic ratio varied between 130 to below 10 in some patients. CONCLUSION: The results were compared with published data. We found clearly skewed distribution of tumor doses, with a majority of tumors receiving only a few mGy per MBq administered activity. In some patients, however, doses did reach 20 mGy MBq(-1).     

Dose-related effects of Ampligen (poly(I).poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis

The antifibrotic effect of the mismatched double-stranded RNA, Ampligen (poly(I).poly(C12U)), was evaluated in a bleomycin-mouse model of pulmonary fibrosis. Mice received a single intratracheal dose of bleomycin (0.125 U/mouse) or saline (50 microL) at the beginning of the experiment, followed by 5 or 6 intraperitoneal injections of Ampligen (1.0, 5.0, 10.0, 15.0, or 25.0 mg/kg) or saline at regular intervals for 2 weeks. Ampligen did not produce increased mortality or weight loss by itself. However, it produced varying degrees of mortality in combination with bleomycin. Five injections of 10 mg/kg Ampligen or three injections of 25 mg/kg Ampligen plus three injections of 10 mg/kg Ampligen in combination with bleomycin .produced significant reductions in lung collagen accumulation as indicated by lung hydroxyproline content compared to the bleomycin control group. Animals receiving bleomycin plus Ampligen at all dosages had significantly reduced prolyl hydroxylase activity compared to the bleomycin control group. Lipid peroxidation and bronchoalveolar lavage fluid (BALF)-supernatant protein content for the groups receiving bleomycin plus Ampligen were not reduced compared to the bleomycin control group. In the BALF-supernatant, the activity of acid phosphatase, a lysosomal enzyme produced by neutrophils, monocytes, and macrophages, was significantly decreased in the group receiving bleomycin plus 10 mg/kg Ampligen. Also, selected BALF differential immune cell counts were reduced in some of the groups receiving bleomycin plus Ampligen, but not in a consistent or dose-dependent manner. The results of this study indicate that Ampligen can significantly reduce the bleomycin-induced increased collagen accumulation and may be therapeutically useful in the management of lung fibrosis in humans.     

Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives

A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic activity. In this work, 8 new compounds of this class were synthesized using usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5-chloropyrazole-1-phenyl derivative and subsequent reaction with several nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4-nitro-1-phenylpyrazole which was the most potent in this series, presenting an analgesic action comparable to that show by dipyrone.     

Temperature-regulated expression of the tac/lacl system for overproduction of a fungal xylanase in Escherichia coli

Temperature-regulated expression of recombinant proteins in the tac promoter (Ptac) system was investigated. Expression levels of fungal xylanase and cellulase from N. patriciarum in E. coli strains containing the natural lacI gene under the control of the Ptac markedly increased with increasing cultivation temperature in the absence of a chemical inducer. The specific activities (units per milligram protein of crude enzyme) of the fungal xylanase and cellulase produced from recombinant E. coli strain pop2136 grown at 42 degrees C were about 4.5 times higher than those of the cells grown at 23 degrees C and were even slightly higher when compared with cells grown in the presence of the inducer isopropyl beta-D-thiogalactopyranoside. The xylanase expression level in the temperature-regulated Ptac system was about 35% of total cellular protein. However, this system can not be applied to E. coli strains containing lacIq, which confers over production of the lac repressor, for high-level expression of recombinant proteins. In comparison with the lambda PL system, the Ptac-based xylanase plasmid in E. coli pop2136 gave a considerably higher specific activity of the xylanase than did the best lambda PL-based construct using the same thermal induction procedure. The high-level expression of the xylanase using the temperature-regulated Ptac system was also obtained in 10-litre fermentation studies using a fed-batch process. These results unambiguously demonstrated that the temperature-modulated Ptac system can be used for overproduction of some non-toxic recombinant proteins.     

Cholesterol oxides accumulate in human cataracts

Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose transport by aortic endothelium. High glucocorticoid doses are used for many diseases, but with unknown effects on brain glucose transport or metabolism. This study tested the hypothesis that glucocorticoids affect glucose transport or metabolism by brain microvascular endothelium. Male rats received dexamethasone (DEX) s.c. with sucrose feeding for up to seven days. Cerebral microvessels from rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose extraction compared to controls. Glucose transport in vivo correlated with hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted hyperinsulinemia and prevented increased glucose extraction induced by DEX. In contrast, isolated brain microvessels exposed to DEX in vitro demonstrated suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner that requires the effects of chronic hyperinsulinemia. These effects override any direct inhibitory effects of either hyperglycemia or DEX.     

Image segmentation towards new image representation methods

Very low bit-rate video coding has recently become one of the most important areas of image communication and a large variety of applications have already been identified. Since conventional approaches are reaching a saturation point, in terms of coding efficiency, a new generation of video coding techniques, aiming at a deeper “understanding” of the image, is being studied. In this context, image analysis, particularly the identification of objects or regions in images (segmentation), is a very important step. This paper describes a segmentation algorithm based on split and merge. Images are first simplified using mathematical morphology operators, which eliminate perceptually less relevant details. The simplified image is then split according to a quad tree structure and the resulting regions are finally merged in three steps: merge, elimination of small regions and control of the number of regions.     

Vapor pressure measurements of para-hydrogen adsorbed on exfoliated graphite

Monolayer isotherms were measured for 15, 18, and 20 K for para-hydrogen adsorbed on exfoliated graphite foam, and for the second, third, and fourth layers in the temperature interval of 8 to 20 K, using the standard volumetric method. From the data, the isosteric heat of adsorption, molar entropies and internal energies were obtained as a function of coverage. The values for coverages above the third layer were compared to those at the p-H₂ bulk triple point, showing that, within our experimental uncertainty, the results are closer to the values of bulk solid para-hydrogen. Critical temperatures for the second and third layers and the triple point temperature for the second layer, were determined, yielding values of T_c2 = (10.0±0.1) K, T_c3 = (11.0±0.5) K and T_t2 = (6.5±0.1) K respectively. Features occurring along the monolayer coverages are compared to transitions which occur in the para-hydrogen phase diagrams adsorbed on graphite, obtained from heat capacity measurements by other authors. From the isotherms, compressibilities were calculated as a function of coverage for several temperatures. Whenever possible the obtained results were compared to existing data in the literature.     

The transient state in the oxidation of binary alloys forming the most-stable oxide: A numerical solution

The initial transient high-temperature oxidation stage for binary alloys forming the most-stable oxide has been examined by means of a numerical procedure based on the finite-difference method. At variance with previous models, the present treatment takes into account the effect of the rate of the reaction at the scale/gas interface over the corrosion kinetics. The calculations concerning the transient stage are developed either using the general parabolic rate law to represent the overall scaling kinetics or using the rate law of the reaction at the scale/gas interface as a boundary condition without imposing any particular rate law to the overall process. A correct analysis of the oxidation behavior of binary alloys during the transient stage must take into account the kinetics effect of the rate of the surface reaction. The concentration of the most-reactive element at the alloy/scale interface changes regularly with time, decreasing gradually from the initial bulk value to its final steady-state value. The present results are in good agreement with those obtained by means of an approximate analytical model developed previously.     

The effect of grazing intensity and the presence of a forage legume on nitrogen dynamics in Brachiaria pastures in the Atlantic forest region of the south of Bahia, Brazil

It has been shown that with careful grazing management and addition of Pand K, but not N, fertilisers Brachiaria pastures are ableto maintain sustainable live weight gains over many years. However, standardon-farm practice, which generally involves high stocking rates, leads after afew years to pasture decline due mainly to N deficiency for grass regrowth. Togenerate an understanding of the mechanism of pasture decline and possiblemanagement options to mitigate this process, a study was performed in theAtlantic forest region of the south of Bahia state to study the N dynamics inpastures of Brachiaria humidicola subject to threedifferent stocking rates of beef cattle, with and without the presence of theforage legume Desmodium ovalifolium. Despite the fact thatthe C:N ratio of the deposited litter was high (60 to 70) the rate ofdecomposition was very rapid (k –0.07 gg^–1 day^–1) and annual rates of Nturnover through the litter pathway were between 105 and 170 kg Nha^–1 year^–1. In the grass-onlypasturesas stocking rate increased from 2 to 3 head ha^–1, N recycledinthe litter decreased by 11%, but a further increase to 4 headha^–1 decreased N recycling by 30% suggesting thatbeyonda certain critical level higher grazing stocking rates would lead to pasturedecline if there was no N addition. High stocking rates decreased theproportionof the legume in the sward, but at all rates the concentration of N in both thegreen and dead grass in the forage on offer and in the litter was higher in themixed sward. The presence of the legume caused a decrease in the C:N ratio ofthe microbial biomass while both soil N mineralisation and nitrificationincreased. This increased rate of turnover of the microbial biomass and thecontribution of N₂ fixation to the legume resulted in largeincreasesin the N recycled via litter deposition ranging from 42 to 155 kg Nha^–1 year^–1.