Prednisolone disposition in steroid-dependent asthmatics

A 40-mg intravenous dose of prednisolone was given as prednisolone phosphate to seven severe steroid-dependent asthmatics and to 13 healthy volunteers to determine if the large prednisone requirements of these patients were a function of the disease, cellular response, or rapid clearance of prednisolone. Plasma concentrations of prednisolone, prednisone, and cortisol were determined by high-performance liquid chromatography over an 8-hr test period. Circulating eosinophil concentrations were monitored concurrently. The apparent half-lifes of prednisolone in the asthmatics and normals were 3.33 +/- 0.71 and 3.25 +/- 0.58 hr (mean +/- SD). The apparent plasma clearances of prednisolone were 201 +/- 54 and 198 +/- 38 ml/min/1.73 m2 and the apparent volumes of distribution were 50.8 +/- 11.7 and 53.5 +/- 13.5 L/1.73 m2 for the asthmatic and normal groups, respectively. When the concentration-dependent binding of prednisolone to plasma protein was examined, no differences in the apparent clearances of unbound drug were found between the two groups. The eosinopenic response to prednisolone was similar in the steroid-dependent asthmatics and healthy normal volunteers. These studies indicate that binding, distribution, and clearance of prednisolone are not responsible for the large prednisone requirement of some steroid-dependent asthmatics. Differences in steroid-receptor sensitivity or in severity or pathophysiology of the disease state more likely account for the need for large prednisone dosages in these patients.     

Reversal of pretreatment hypotension and control of hemorrhage in trauma patients by a simple device

The injection of a suspension of Walker 256 carcinoma cells into the carotid artery of rats produced a model of hematogenously spread cerebral metastases. Most animals died from massive extracerebral tumors of the head and jaw; brain tumors were present in only one-quarter. External carotid artery ligation prior to tumor inoculation did not increase the incidence of fatal brain tumor. When cyclophosphamide, 15 mg/kg, was injected as a single dose on the fourteenth day after tumor inoculation, most of the extracerebral tumor disappeared. Fifty percent of the animals so treated were cured of tumor, but 90% of the remainder died of large intracerebral tumors. Severe cytopathic changes resulting from cyclophosphamide were present in extracerebral or choroid plexus tumors but were mild or nonexistent in intracerebral tumors. These selective effects of cyclophosphamide suggest that water-soluble agents are less effective against tumor in the brain than against extracerebral tumors despite the fact that metastatic tumor breaks down the blood-brain barrier.     

Low-dispersion turns and junctions for microchannel systems

Numerical methods are employed to optimize the geometry of two-dimensional microchannel turns such that the turn-induced spreading of a solute band is minimized. An inverted numerical method is first developed to compute the electric potential and local species motion in turns of arbitrary geometry. The turn geometry is then optimized by means of a nonlinear least-squares minimization algorithm using the spatial variance of the species distribution leaving the turn as the object function. This approach yields the turn geometry producing the minimum possible dispersion, subject only to prescribed constraints. The resulting low-dispersion turns provide an induced variance 2-3 orders of magnitude below that of a comparable conventional turns. Sample results are presented for 180 and 90 degrees turns, and the use of these turns to form wyes and tees is discussed. A sample 45 degrees wye is presented. The use of low-dispersion turns in folding separation columns is also discussed, and sample calculations are presented for folding a column 100 microm in width and up to 900 mm in length onto a region of only 10 by 10 mm. These low-dispersion geometries are applicable to electroosmosis, electrophoresis, and some pressure-driven flows.     

Enhancement of pasta antioxidant activity with oregano and carrot leaf

Five different pasta formulations were prepared using different concentrations of carrot leaf meal (CLM) and oregano leaf meal (OLM). One control formulation (wheat flour and semolina, 70:30 w/w) and four other formulations were prepared using the following amounts of leaf meals: 5% CLM and 5% OLM (I), 10% CLM (II), 10% OLM (III), and 10% CLM, 10% OLM (IV). The highest content of alpha-linolenic acid was found in formulations II and IV, which also had a reduced n-6/n-3 ratio, 3.6 (IV), when compared to the control, which was 19.8. All the samples enhanced with leaf meals showed antioxidant activity by the DPPH radical method; however, it was higher in formulation IV, which was the same observed for phenolic compounds. Pasta added with leaf meals lost more solubles, had shorter cooking time and a lower weight increase than the control pasta. All formulations had significant sensory acceptance.     

Solar photocatalytic degradation of real textile effluents by associated titanium dioxide and hydrogen peroxide

The present work investigated the photodegradation of real textile effluents by advanced oxidative process (AOP) using TiO₂/H₂O₂/sunlight system. The procedures were carried out at ambient conditions in March 2005. The results were evaluated by COD reduction concomitant to the increase in inorganic ion concentration (mineralization) and the analysis of the effluent characteristic spectral wavelengths: 228, 254, and 284 nm (simple aromatic compounds), 310 nm (conjugated aromatic compounds), and 390, 450, and 530 (color). As this study is not restricted to the decolorization process, it allows a more reliable evaluation of effluent mineralization. The results indicate that solar radiation is as efficient as or even more efficient than artificial radiation was in previous studies and that it also allows a reduction in effluent treatment operational costs.     

High-resolution crystal structures of delta5-3-ketosteroid isomerase with and without a reaction intermediate analogue

Bacterial Delta5-3-ketosteroid isomerase (KSI) catalyzes a stereospecific isomerization of steroid substrates at an extremely fast rate, overcoming a large disparity of pKa values between a catalytic residue and its target. The crystal structures of KSI from Pseudomonas putida and of the enzyme in complex with equilenin, an analogue of the reaction intermediate, have been determined at 1.9 and 2.5 A resolution, respectively. The structures reveal that the side chains of Tyr14 and Asp99 (a newly identified catalytic residue) form hydrogen bonds directly with the oxyanion of the bound inhibitor in a completely apolar milieu of the active site. No water molecule is found at the active site, and the access of bulk solvent is blocked by a layer of apolar residues. Asp99 is surrounded by six apolar residues, and consequently, its pKa appears to be elevated as high as 9.5 to be consistent with early studies. No interaction was found between the bound inhibitor and the residue 101 (phenylalanine in Pseudomonas testosteroni and methionine in P. putida KSI) which was suggested to contribute significantly to the rate enhancement based on mutational analysis. This observation excludes the residue 101 as a potential catalytic residue and requires that the rate enhancement should be explained solely by Tyr14 and Asp99. Kinetic analyses of Y14F and D99L mutant enzymes demonstrate that Tyr14 contributes much more significantly to the rate enhancement than Asp99. Previous studies and the structural analysis strongly suggest that the low-barrier hydrogen bond of Tyr14 (>7.1 kcal/mol), along with a moderate strength hydrogen bond of Asp99 ( approximately 4 kcal/mol), accounts for the required energy of 11 kcal/mol for the transition-state stabilization.     

Information from time-varying vibrotactile stimuli

Experiments have been carried out to investigate the information transfer available via a single vibrator on the fingertip. In a first experiment, for stimuli with durations 80 to 320 ms, discrimination of a one-octave step change in frequency at the halfway point was investigated. Results were similar for three stimulus types--sinewave, monophasic pulse and tetraphasic pulse--suggesting temporal cues are more important than spectral cues in this task. In a second experiment, subjects were required to perceive changes in a sequence of stimulus elements. A presentation rate of 6.25 elements s-1 was found to give better results than a rate of 12.5 elements s-1. In the former case, the potential information transfer per element was estimated to be approximately 1.0 bits, corresponding to an information transfer rate of around 6 bits s-1. Implications for the design of a tactile aid to lipreading are discussed.